U.S. patent application number 10/753213 was filed with the patent office on 2004-09-02 for polycyclic aryl and heteroaryl substituted 1, 4-quinones useful for selective inhibition of the coagulation cascade.
This patent application is currently assigned to Pharmacia Corporation. Invention is credited to Parlow, John J., South, Michael S..
Application Number | 20040171839 10/753213 |
Document ID | / |
Family ID | 26893352 |
Filed Date | 2004-09-02 |
United States Patent
Application |
20040171839 |
Kind Code |
A1 |
South, Michael S. ; et
al. |
September 2, 2004 |
Polycyclic aryl and heteroaryl substituted 1, 4-quinones useful for
selective inhibition of the coagulation cascade
Abstract
The invention relates to polycyclic aryl and heteroaryl
substituted 1,4-quinone compounds useful as inhibitors of serine
proteases of the coagulation cascade and compounds, compositions
and methods for anticoagulant therapy for the treatment and
prevention of a variety of thrombotic conditions including coronary
artery and cerebrovascular diseases.
Inventors: |
South, Michael S.; (St.
Louis, MO) ; Parlow, John J.; (Arnold, MO) |
Correspondence
Address: |
SENNIGER POWERS LEAVITT AND ROEDEL
ONE METROPOLITAN SQUARE
16TH FLOOR
ST LOUIS
MO
63102
US
|
Assignee: |
Pharmacia Corporation
|
Family ID: |
26893352 |
Appl. No.: |
10/753213 |
Filed: |
January 7, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10753213 |
Jan 7, 2004 |
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09829739 |
Apr 10, 2001 |
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6686484 |
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60197975 |
Apr 17, 2000 |
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60252333 |
Nov 20, 2000 |
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Current U.S.
Class: |
546/340 ;
548/146; 548/215; 548/335.1; 552/296 |
Current CPC
Class: |
C07C 2601/02 20170501;
C07C 2601/04 20170501; C07C 2602/42 20170501; C07D 295/13 20130101;
C07C 2601/14 20170501; A61P 35/00 20180101; A61P 11/00 20180101;
C07C 2601/18 20170501; C07C 2601/16 20170501; A61P 9/00 20180101;
A61P 9/10 20180101; A61P 7/02 20180101; C07C 2601/08 20170501; C07C
257/18 20130101 |
Class at
Publication: |
546/340 ;
548/146; 548/215; 548/335.1; 552/296 |
International
Class: |
C07D 277/08; C07D
263/02; C07D 213/46 |
Claims
What we claim is:
1. A compound having the Formula (1): 76or a pharmaceutically
acceptable salt thereof, wherein; B is formula (V): 77wherein
D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are independently
selected from the group consisting of C, N, O, S and a covalent
bond with the provisos that no more than one is a covalent bond, no
more than one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 is
O, no more than one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and
K.sup.1 is S, one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1
must be a covalent bond when two of D.sup.1, D.sup.2, J.sup.1,
J.sup.2 and K.sup.1 are O and S, and no more than four of D.sup.1,
D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are N with the proviso that
R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are each
independently selected to maintain the tetravalent nature of
carbon, trivalent nature of nitrogen, the divalent nature of
sulfur, and the divalent nature of oxygen; R.sup.32, R.sup.33,
R.sup.34, R.sup.35, and R.sup.36 are independently selected to be
Q.sup.b; R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.16,
R.sup.17, R.sup.18, R.sup.19, R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36 are independently selected from the group
consisting of hydrido, amidino, guanidino, dialkylsulfonium,
trialkylphosphonium, dialkylsulfoniumalkyl, carboxy,
heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl,
acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl,
aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl,
aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl,
aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl,
cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylisulfonyl,
cycloalkylsulfonylalkyl, heteroarylamino,
N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl,
haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl,
heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl,
cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy,
halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy,
halocycloalkenyloxyalkyl, hydroxy, amino, alkoxyamino, thio, nitro,
lower alkylamino, alkylthio, alkylthioalkyl, arylamino,
aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl,
alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl,
arylsulfonylalkyl, heteroarylsulfinylalkyl,
heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl,
haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,
alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl
amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido,
diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl,
arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl,
heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio,
alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl,
heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl,
alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy,
cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower
cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl,
haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl,
hydroxyalkyl, aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl,
aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated
heterocyclyl, partially saturated heterocyclyl, heteroaryl,
heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl,
arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy,
alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido,
carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamindo,
carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono,
phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl;
R.sup.32 and R.sup.33, R.sup.33 and R.sup.34, R.sup.34 and
R.sup.35, and R.sup.35 and R.sup.36 substituent pairs are
independently selected to form a spacer pair wherein a spacer pair
is taken together to form a linear moiety having from 3 through 6
contiguous atoms connecting the points of bonding of said spacer
pair members to form a ring selected from the group consisting of a
cycloalkenyl ring having 5 through 8 contiguous members, a
partially saturated heterocyclyl ring having 5 through 8 contiguous
members, a heteroaryl ring having 5 through 6 contiguous members,
and an aryl with the proviso that no more than one of the group
consisting of spacer pairs R.sup.32 and R.sup.33, R.sup.33 and
R.sup.34, R.sup.34 and R.sup.35, and R.sup.35 and R.sup.36 are used
at the same time; B is formula (VI): 78wherein D.sup.3, D.sup.4,
J.sup.3, and J.sup.4 are independently selected from the group
consisting of C, N, O, and S, no more than one of D.sup.3, D.sup.4,
J.sup.3, and J.sup.4 is O, no more than one of D.sup.3, D.sup.4,
J.sup.3, and J.sup.4is S, and no more than three of D.sup.1,
D.sup.2, J.sup.1, and J.sup.2 are N with the proviso that R.sup.32,
R.sup.33, R.sup.34, and R.sup.35 are each independently selected to
maintain the tetravalent nature of carbon, trivalent nature of
nitrogen, the divalent nature of sulfur, and the divalent nature of
oxygen; B is selected from the group consisting of C3-C8 alkyl,
C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8
haloalkenyl wherein each member of group B may be optionally
substituted at any carbon up to and including 6 atoms from the
point of attachment of B to A with one or more of the group
consisting of R.sub.32, R.sub.33, R.sub.34, R.sub.35, and R.sub.36;
B is selected from the group consisting of C3-C10 cycloalkyl,
C5-C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9
partially saturated heterocyclyl, wherein each ring carbon may be
optionally substituted with R.sub.33, a ring carbon other than the
ring carbon at the point of attachment of B to A may be optionally
substituted with oxo provided that no more than one ring carbon is
substituted by oxo at the same time, ring carbon and nitrogen atoms
adjacent to the carbon atom at the point of attachment may be
optionally substituted with R.sub.9 or R.sub.13, a ring carbon or
nitrogen atom adjacent to the R.sub.9 position and two atoms from
the point of attachment may be substituted with R.sub.10, a ring
carbon or nitrogen atom adjacent to the R.sub.13 position and two
atoms from the point of attachment may be substituted with
R.sub.12, a ring carbon or nitrogen atom three atoms from the point
of attachment and adjacent to the R.sub.10 position may be
substituted with R.sub.11, a ring carbon or nitrogen atom three
atoms from the point of attachment and adjacent to the R.sub.12
position may be substituted with R.sub.33, and a ring carbon or
nitrogen atom four atoms from the point of attachment and adjacent
to the R.sub.11 and R.sub.33 positions may be substituted with
R.sub.34; R.sup.9 and R.sup.10, R.sup.10 and R.sup.11, R.sup.11 and
R.sup.12 and R.sup.12 and R.sup.13 spacer pairs are independently
selected to form a spacer pair wherein a spacer pair is taken
together to form a linear moiety having from 3 through 6 contiguous
atoms connecting the points of bonding of said spacer pair members
to form a ring selected from the group consisting of a cycloalkenyl
ring having 5 through 8 contiguous members, a partially saturated
heterocyclyl ring having 5 through 8 contiguous members, a
heteroaryl ring having 5 through 6 contiguous members, and an aryl
with the proviso that no more than one of the group consisting of
spacer pairs R.sup.9 and R.sup.10, R.sup.10 and R.sup.11, R.sup.11
and R.sup.12, and R.sup.12 and R.sup.13 is used at the same time; A
is selected from the group consisting of single covalent bond,
(W.sup.7).sub.rr--(CH(R.sup.15)).sub.pa and
(CH(R.sup.15)).sub.pa--(W.sup- .7).sub.rr wherein rr is an integer
selected from 0 through 1, pa is an integer selected from 0 through
6, and W.sup.7 is selected from the group consisting of O, S, C(O),
C(S), C(O)S, C(S)O, C(O)N(R.sup.7), C(S)N(R.sup.7), (R.sup.7)NC(O),
(R.sup.7)NC(S), S(O), S(O).sub.2, S(O).sub.2N(R.sup.7),
(R.sup.7)NS(O).sub.2, Se(O), Se(O).sub.2,
Se(O).sub.2N(R.sup.7),(R.sup.7)NSe(O).sub.2, P(O)(R.sup.8),
N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7),
C(NR.sup.7)N(R.sup.7), (R.sup.7)NC(NR.sup.7), and N(R.sup.7)
R.sup.7 and R.sup.8 are independently selected from the group
consisting of hydrido, hydroxy, alkyl, alkenyl, aryl, aralkyl,
aryloxy, alkoxy, alkenyloxy, alkylthio, alkylamino, arylthio,
arylamino, acyl, aroyl, heteroaroyl, aralkoxyalkyl,
heteroaralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, alkenyloxyalkyl,
alkylthioalkyl, arylthioalkyl, aralkoxyalkyl, heteroaralkoxyalkyl,
alkylsulfinylalkyl, alkylsulfonylalkyl, heteroaryl, heteroaryloxy,
heteroarylamino, heteroaralkyl, heteroaralkyloxy,
heteroaralkylamino, and heteroaryloxyalkyl; R.sup.14, R.sup.15,
R.sup.37, R.sup.38, R.sup.39, R.sup.40, R.sup.41 and R.sup.42 are
independently selected from the group consisting of hydrido,
hydroxy, halo, cyano, aryloxy, amino, alkylamino, dialkylamino,
hydroxyalkyl, aminoalkyl, acyl, aroyl, heteroaroyl,
heteroaryloxyalkyl, sulfhydryl, acylamido, alkoxy, alkylthio,
arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl,
aralkoxyalkylalkoxy, alkylsulfinylalkyl, alkylsulfonylalkyl,
aralkylthioalkyl, heteroaralkoxythioalkyl, alkoxyalkyl,
heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl,
cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl,
cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl,
halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl,
halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl,
saturated heterocyclyl, partially saturated heterocyclyl,
heteroaryl, heteroarylalkyl, heteroarylthioalkyl,
heteroaralkylthioalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl,
monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfinyl,
alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl,
arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl,
aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl,
cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkl,
heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl,
heteroarylsulfinylalkyl, aralkylsulfinylalkyl,
aralkylsulfonylalkyl, carboxy, carboxyalkyl, carboalkoxy,
carboxamide, carboxamidoalkyl, carboaralkoxy, trialkylsilyl,
dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl, and
diaralkoxyphosphonoalkyl; R.sup.14 and R.sup.14, when bonded to
different carbons, are taken together to form a group selected from
the group consisting of covalent bond, alkylene, haloalkylene, and
a linear moiety spacer selected to form a ring selected from the
group consisting of cycloalkyl ring having from 5 through 8
contiguous members, cycloalkenyl ring having from 5 through 8
contiguous members, and a heterocyclyl having from 5 through 8
contiguous members; R.sup.14 and R.sup.15, when bonded to different
carbons, are taken together to form a group selected from the group
consisting of covalent bond, alkylene, haloalkylene, and a linear
moiety spacer selected to form a ring selected from the group
consisting of a cycloalkyl ring having from 5 through 8 contiguous
members, a cycloalkenyl ring having from 5 through 8 contiguous
members, and a heterocyclyl having from 5 through 8 contiguous
members; R.sup.15 and R.sup.15, when bonded to different carbons,
are taken together to form a group selected from the group
consisting of covalent bond, alkylene, haloalkylene, and a linear
moiety spacer selected to form a ring selected from the group
consisting of cycloalkyl ring having from 5 through 8 contiguous
members, cycloalkenyl ring having from5 through 8 contiguous
members, and a heterocyclyl having from 5 through 8 contiguous
members; R.sup.14 and R.sup.15, when bonded to the same carbon, are
taken together to form a group selected from a group consisting of
oxo, thiono, alkylene, haloalkylene, and a linear moiety spacer
selected to form a ring selected from the group consisting of
cycloalkyl ring having from 5 through 8 contiguous members,
cycloalkenyl ring having from 5 through 8 contiguous members, and a
heterocyclyl having from 5 through 8 contiguous members; .PSI. is
selected from the group consisting of NR.sup.5, O, C(O), C(S), S,
S(O), S(O).sub.2, ON(R.sup.5), P(O)(R.sup.8), and
CR.sup.39R.sup.40; R.sup.5 is selected from the group consisting of
hydrido, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxy, alkoxy,
alkenyloxy, alkylthio, arylthio, aralkoxyalkyl,
heteroaralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, alkenyloxyalkyl,
alkylthioalkyl, arylthioalkyl, aralkoxyalkyl, heteroaralkoxyalkyl,
alkylsulfinylalkyl, alkylsulfonylalkyl, cycloalkyl,
cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl,
cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl,
halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl,
halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, heteroaryl,
heteroarylalkyl, monocarboalkoxyalkyl, monocarboalkoxy,
dicarboalkoxyalkyl, monocarboxamido, monocyanoalkyl, dicyanoalkyl,
carboalkoxycyanoalkyl, acyl, aroyl, heteroaroyl,
heteroaryloxyalkyl, and dialkoxyphosphonoalkyl; X.sup.0 and R.sup.2
are independently selected from the group consisting of Z.sup.0-Q,
hydrido, alkyl, alkenyl, and halo; X.sup.0 and R.sup.2 are
independently selected from the group consisting of amidino,
guanidino, dialkylsulfonium, trialkylphosphonium,
dialkylsulfoniumalkyl, heteroarylamino, amino, nitro, alkylamino,
arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl,
aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl,
cyano, and phosphono; X.sup.0 and R.sup.5 are taken together to
form a spacer pair wherein the spacer pair forms a linear spacer
moiety having from 2 through 5 contiguous atoms connecting the
points of bonding of said spacer pair members to form a
heterocyclyl ring having from 5 through 8 contiguous members;
X.sup.0 and R.sup.39 are taken together to form a spacer pair
wherein the spacer pair forms a linear spacer moiety having from 2
through 5 contiguous atoms connecting the points of bonding of said
spacer pair members to form a heterocyclyl ring having from 5
through 8 contiguous members; X.sup.0 and R.sup.40 are taken
together to form a spacer pair wherein the spacer pair forms a
linear spacer moiety having from 2 through 5 contiguous atoms
connecting the points of bonding of said spacer pair members to
form a heterocyclyl ring having from 5 through 8 contiguous
members; X.sup.0 is selected to form a linear moiety having from 2
through 5 contiguous atoms linked to the points of bonding of both
R.sup.39 and R.sup.40 to form a heterocyclyl ring having from 5
through 8 contiguous members; R.sup.2 and R.sup.4a, R.sup.2 and
R.sup.4b, R.sup.2 and R.sup.14, and R.sup.2 and R.sup.15 spacer
pairs are independently selected to form spacer pairs wherein a
spacer pair is taken together to form a linear moiety having from 2
through 5 contiguous atoms connecting the points of bonding of said
spacer pair members to form a heterocyclyl ring having from 5
through 8 contiguous members with the proviso that no more than one
of the group of spacer pairs consisting of R.sup.2 and R.sup.4a,
R.sup.2 and R.sup.4b, R.sup.2 and R.sup.2 , and R.sup.2 and
R.sup.15 is used at the same time; R.sup.2 is independently
selected to form a linear moiety having from 2 through 5 contiguous
atoms linked to the points of bonding of both R.sup.4a and R.sup.4b
to form a heterocyclyl ring having from 5 through 8 contiguous
members; Z.sup.0 is selected from the group consisting of covalent
single bond, (CR.sup.41R.sup.42).sub.q wherein q is an integer
selected from 1 through 6, (CH(R.sup.41)).sub.g--W.sup.0--(-
CH(R.sup.42)).sub.p wherein g and p are integers independently
selected from 0 through 3 and W.sup.0 is selected from the group
consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,
C(O)N(R.sup.41), (R.sup.41)NC(O), C(S)N(R.sup.41), (R.sup.41)NC(S),
OC(O)N(R.sup.41),(R.sup.41)NC(O)O,
SC(S)N(R.sup.41),(R.sup.41)NC(S)S, SC(O)N(R.sup.41),
(R.sup.41)NC(O)S, OC(S)N(R.sup.41), (R.sup.41)NC(S)O,
N(R.sup.42)C(O)N(R.sup.41), (R.sup.41)NC(O)N(R.sup.42),
N(R.sup.42)C(S)N(R.sup.41), (R.sup.41)NC(S)N(R.sup.42), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.41), N(R.sup.41)S(O).sub.2, Se,
Se(O), Se(O).sub.2, Se(O).sub.2N(R.sup.41), N(R.sup.41)Se(O).sub.2,
P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7),
N(R.sup.41), ON(R.sup.41), and SiR.sup.28R.sup.29, and
(CH(R.sup.41)).sub.e--W.sup.2--- (CH(R.sup.42)).sub.h wherein e and
h are integers independently selected from 0 through 2 and W.sup.2
is selected from the group consisting of CR.sup.41.dbd.CR.sup.42,
CR.sup.41R.sup.42.dbd.C; vinylidene), and ethynylidene (C.ident.C;
1,2-ethynyl), with the provisos that R.sup.41 and R.sup.42 are
selected from other than halo and cyano when directly bonded to N
and Z.sup.0 is directly bonded to the quinone ring; Q is formula
(II): 79wherein D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are
independently selected from the group consisting of C, N, O, S and
a covalent bond with the provisos that no more than one is a
covalent bond, no more than one of D.sup.1 , D.sup.2, J.sup.1,
J.sup.2 and K.sup.1 is O, no more than one of D.sup.1, D.sup.2 ,
J.sup.1, J.sup.2 and K.sup.1 is S, one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 must be a covalent bond when two of
D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are O and S, and no
more than four of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and
K.sup.1 are N, with the proviso that R.sup.9, R.sup.10, R.sup.11,
R.sup.12, and R.sup.13 are each independently selected to maintain
the tetravalent nature of carbon, trivalent nature of nitrogen, the
divalent nature of sulfur, and the divalent nature of oxygen; Q is
formula (III): 80wherein D.sup.3, D.sup.4, J.sup.3, and J.sup.4 are
independently selected from the group consisting of C, N, O, and S,
no more than one of D.sup.3, D.sup.4, J.sup.3, and J.sup.4 is O, no
more than one of D.sup.3, D.sup.4, J.sup.3 and J.sup.4 is S, and no
more than three of D.sup.1, D.sup.2, J.sup.1, and J.sup.2 are N
with the proviso that R.sup.9, R.sup.10, R.sup.11, and R.sup.12 are
each independently selected to maintain the tetravalent nature of
carbon, trivalent nature of nitrogen, the divalent nature of
sulfur, and the divalent nature of oxygen; Q is selected from the
group consisting of alkyl, alkoxy, alkylamino, alkylthio,
haloalkylthio, alkenyl, alkynyl, saturated heterocyclyl, partially
saturated heterocyclyl, acyl, aroyl, heteroaroyl, cycloalkyl,
cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl,
cycloalkylalkenyl, haloalkyl, haloalkoxy, haloalkenyl,
halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl,
haloalkenyloxyalkyl, halocycloalkoxyalkyl, and
halocycloalkenyloxyalkyl; K is (CR.sup.4aR.sup.4b).sub.n wherein n
is an integer selected from 1 through 4; R.sup.4a and R.sup.4b are
independently selected from the group consisting of halo, hydrido,
hydroxy, cyano, hydroxyalkyl, alkyl, alkenyl, aryl, aralkyl,
aralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, heteroaryloxyalkyl,
alkenyloxyalkyl, alkylthioalkyl, aralkylthioalkyl, arylthioalkyl,
cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkenyl, heteroaryl,
heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl,
cyanoalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl,
haloalkylsulfinyl, arylsulfinylalkyl, arylsulfonylalkyl,
heteroarylsulfonylalkyl, heteroarylsulfinylalkyl,
aralkylsulfinylalkyl, and aralkylsulfonylalkyl; R.sup.4a and
R.sup.4b, when bonded to the same carbon, are taken together to
form a group selected from the group consisting of oxo, thiono, and
a linear spacer moiety having from 2 through 7 contiguous atoms
connected to form a ring selected from the group consisting of a
cycloalkyl ring having 3 through 8 contiguous members, a
cycloalkenyl ring having 5 through 8 contiguous members, and a
heterocyclyl ring having 5 through 8 contiguous members; E.sup.0 is
E.sup.1, when K is (CR.sup.4aR.sup.4b).sub- .n, wherein E.sup.1 is
selected from the group consisting of a covalent single bond, O, S,
C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.7),
(R.sup.7)NC(O), C(S)N(R.sup.7), (R.sup.7)NC(S), OC(O)N(R.sup.7),
(R.sup.7)NC(O)O, SC(S)N(R.sup.7), (R.sup.7)NC(S)S, SC(O)N(R.sup.7),
(R.sup.7)NC(O)S, OC(S)N(R.sup.7),(R.sup.7)NC(S)O,
N(R.sup.8)C(O)N(R.sup.7), (R.sup.7)NC(O)N(R.sup.8),
N(R.sup.8)C(S)N(R.sup.7), (R.sup.7)NC(S)N(R.sup.8), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.7), N(R.sup.7)S(O).sub.2,
S(O).sub.2N(R.sup.7)C(O), C(O)N(R.sup.7)S(O).sub.2, Se, Se(O),
Se(O).sub.2, Se(O).sub.2N(R.sup.7), N(R.sup.7)Se(O).sub.2,
P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8) P(O)(R.sup.8)N(R.sup.7),
N(R.sup.7), ON(R.sup.7), SiR.sup.28R.sup.29,
CR.sup.4a.dbd.CR.sup.4b, ethynylidene (C.ident.C; 1,2ethynyl), and
C.dbd.CR.sup.4aR.sup.4b; K is (CH(R.sup.14)).sub.j-T wherein j is
selected from a integer from 0 through 3 and T is selected from the
group consisting of single covalent bond, O, S, and N(R.sup.7) with
the proviso that (CH(R.sup.14)).sub.j is bonded to the quinone
ring; E.sup.0 is E.sup.2, when K is (CH(R.sup.14)).sub.j-T, wherein
E.sup.2 is selected from the group consisting of a covalent single
bond, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.7),
(R.sup.7)NC(O), C(S)N(R.sup.7), (R.sup.7)NC(S), (R.sup.7)NC(O)O,
(R.sup.7)NC(S)S, (R.sup.7)NC(O)S, (R.sup.7)NC(S)O,
N(R.sup.8)C(O)N(R.sup.7), (R.sup.7)NC(O)N(R.sup.8),
N(R.sup.8)C(S)N(R.sup.7), (R.sup.7)NC(S)N(R.sup.8), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.7), N(R.sup.7)S(O).sub.2,
S(O).sub.2N(H)C(O), C(O)N(H)S(O).sub.2, Se(O), Se(O).sub.2,
Se(O).sub.2N(R.sup.7), N(R.sup.7)Se(O).sub.2, P(O)(R.sup.8),
N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7) and N(R.sup.7); K
is G-(CH(R.sup.15)).sub.k wherein k is selected from an integer
from 1 through 3 and G is selected from the group consisting of O,
S, and N(R.sup.7) with the proviso that R.sup.15 is other than
hydroxy, cyano, halo, amino, alkylamino, dialkylamino, and
sulfhydryl when k is 1; E.sup.0 is E.sup.3, when K is
G-(CH(R.sup.15)).sub.k, wherein E.sup.3 is selected from the group
consisting of a covalent single bond, O, S, C(O), C(S), C(O)O,
C(S)O, C(O)S, C(S)S, C(O)N(R.sup.7), (R.sup.7)NC(O),
C(S)N(R.sup.7), (R.sup.7)NC(S), OC(O)N(R.sup.7), (R.sup.7)NC(O)O,
SC(S)N(R.sup.7), (R.sup.7)NC(S)S, SC(O)N(R.sup.7), (R.sup.7)NC(O)S,
OC(S)N(R.sup.7), (R.sup.7)NC(S)O, N(R.sup.7)C(O)N(R.sup.7),
(R.sup.7)NC(O)N(R.sup.8), N(R.sup.8)C(S)N(R.sup.7),
(R.sup.7)NC(S)N(R.sup.8), S(O), S(O).sub.2, S(O).sub.2N(R.sup.7),
N(R.sup.7)S(O).sub.2, Se, Se(O), Se(O).sub.2,
Se(O).sub.2N(R.sup.7), N(R.sup.7)Se(O).sub.2, P(O)(R.sup.8),
N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7), N(R.sup.7),
ON(R.sup.7), SiR.sup.28R.sup.29, CR.sup.4a.dbd.CR.sup.4b,
ethynylidene (C.ident.C; 1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b;
Y.sup.0 is formula (IV): 81wherein D.sup.5, D.sup.6, J.sup.5, and
J.sup.6 are independently selected from the group consisting of C,
N, O, S and a covalent bond with the provisos that no more than one
is a covalent bond, K.sup.2 is independently selected from the
group consisting of C, and N.sup.+, no more than one of D.sup.5,
D.sup.6, J.sup.5, and J.sup.6 is O, no more than one of D.sup.5,
D.sup.6, J.sup.5, and J.sup.6 is S, one of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 must be a covalent bond when two of D.sup.5,
D.sup.6, J.sup.5, and J.sup.6 are O and S, no more than three of
D.sup.5, D.sup.6, J.sup.5, and J.sup.6 are N when K.sup.2 is
N.sup.+, and no more than four of D.sup.5, D.sup.6, J.sup.5, and
J.sup.6 are N when K.sup.2 is carbon with the provisos that
R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are each independently
selected to maintain the tetravalent nature of carbon, trivalent
nature of nitrogen, the divalent nature of sulfur, and the divalent
nature of oxygen; R.sup.16 and R.sup.17 are independently taken
together to form a linear moiety spacer having from 3 through 6
contiguous atoms connected to form a ring selected from the group
consisting of a cycloalkenyl ring having from 5 through 8
contiguous members, a partially saturated heterocyclyl ring having
from 5 through 8 contiguous members, a heteroaryl having from 5
through 6 contiguous members, and an aryl; R.sup.18 and R.sup.19
are independently taken together to form a linear moiety spacer
having from 3 through 6 contiguous atoms connected to form a ring
selected from the group consisting of a cycloalkenyl ring having
from 5 through 8 contiguous members, a partially saturated
heterocyclyl ring having from 5 through 8 contiguous members, a
heteroaryl having from 5 through 6 contiguous members, and an aryl;
Q.sup.b is selected from the group consisting of NR.sup.20R.sup.21,
.sup.+NR.sup.20R.sup.21R.sup.22, oxy, alkyl, alkylaminoalkyl,
aminoalkyl, dialkylsulfoniumalkyl, and acylamino wherein R.sup.20,
R.sup.21, and R.sup.22 are independently selected from the group
consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino,
dialkylamino, aminoalkyl, and hydroxyalkyl with the provisos that
no more than one of R.sup.20, R.sup.21, and R.sup.22 is hydroxy,
alkoxy, alkylamino, amino, and dialkylamino and that R.sup.20,
R.sup.21, and R.sup.22 must be other than be hydroxy, alkoxy,
alkylamino, amino, and dialkylamino when K.sup.2 is N.sup.+;
R.sup.20 and R.sup.21, R.sup.20 and R.sup.22, and R.sup.21 and
R.sup.22 pairs are independently selected to form a spacer pair
wherein a spacer pair is taken together to form a linear moiety
having from 4 through 7 contiguous atoms connecting the points of
bonding of said spacer pair members to form a heterocyclyl ring
having 5 through 8 contiguous members with the proviso that no more
than one of the group consisting of spacer pairs R.sup.20 and
R.sup.21, R.sup.20 and R.sup.22, and R.sup.21 and R.sup.22 is used
at the same time; Q.sup.b is selected from the group consisting of
N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24), N(R.sup.26)C(O)OR.sup.5,
N(R.sup.26)C(O)SR.sup.5, N(R.sup.26 )C(S)OR and
N(R.sup.26)C(S)SR.sup.5 with the proviso that no more than one of
R.sup.23, R.sup.24, and R.sup.26 are hydroxy, alkoxy, alkylamino,
amino, or dialkylamino when two of the group consisting of
R.sup.23, R.sup.24, and R.sup.26 are bonded to the same atom;
Q.sup.b is selected from the group consisting of dialkylsulfonium,
trialkylphosphonium, C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
N(R.sup.26)C(O)N(R.sup.23)(- R.sup.24),
N(R.sup.26)C(S)N(R.sup.23)(R.sup.24C(NR.sup.25)OR.sup.5,
C(O)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
C(S)N(R.sup.26)C(NR.sup- .25)N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R- .sup.24),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24),
C(NR.sup.25)SR.sup.5, C(O)NR.sup.23R.sup.24, and
C(O)NR.sup.23R.sup.24 with the provisos that no more than one of
R.sup.23, R.sup.24, and R.sup.26 is hydroxy, alkoxy, alkylamino,
amino, or dialkylamino when two of the group consisting of
R.sup.23, R.sup.24, and R.sup.26 are bonded to the same atom and
that said Q.sup.b group is bonded directly to a carbon atom;
R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, alkyl, hydroxy,
alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl;
R.sup.23 and R.sup.24 are taken together to form a linear spacer
moiety having from 4 through 7 contiguous atoms connecting the
points of bonding to form a heterocyclyl ring having 5 through 8
contiguous members; R.sup.23 and R.sup.25, R.sup.24 and R.sup.25,
R.sup.25 and R.sup.26, R.sup.24 and R.sup.26, and R.sup.23 and
R.sup.26 pairs are independently selected to form a spacer pair
wherein a spacer pair is taken together from the points of bonding
of selected spacer pair members to form the group L-U--V wherein L,
U, and V are independently selected from the group of
1,2-disubstituted radicals consisting of a cycloalkyl radical, a
cycloalkenyl radical wherein cycloalkyl and cycloalkenyl radicals
are substituted with one or more groups selected from R.sup.30 and
R.sup.31, an aryl radical, an heteroaryl radical, a saturated
heterocyclic radical and a partially saturated heterocyclic radical
wherein said 1,2-substitutents are independently selected from
C.dbd.O, C.dbd.S, C(R.sup.28)R.sup.32, S(O), S(O).sub.2,
OP(OR.sup.31)R.sup.30, P(O)R.sup.30, P(S)R.sup.30 and
Si(R.sup.28)R.sup.29 ; R.sup.23 and R.sup.25, R.sup.24 and
R.sup.25, R.sup.25 and R.sup.26, R.sup.24 and R.sup.26, and
R.sup.23 and R.sup.26 pairs are independently selected to form a
spacer pair wherein a spacer pair is taken together from the points
of bonding of selected spacer pair members to form the group L-U--V
wherein L, U, and V are independently selected from the group of
radicals consisting of 1,2-disubstituted alkylene radicals and
1,2-disubstituted alkenylene radical wherein said 1,2-substitutents
are independently selected from C.dbd.O, C.dbd.S,
C(R.sup.28)R.sup.29, S(O), S(O).sub.2, OP(OR.sup.31)R.sup.30,
P(O)R.sup.30, P(S)R.sup.30, and Si(R.sup.28)R.sup.29 and said
alkylene and alkenylene radical are substituted with one or more
R.sup.30 or R.sup.31 substituents; R.sup.23 and R.sup.25, R.sup.24
and R.sup.25, R.sup.25 and R.sup.26, R.sup.24 and R.sup.26, and
R.sup.23 and R.sup.26 pairs are independently selected to form a
spacer pair wherein a spacer pair is taken together from the points
of bonding of selected spacer pair members to form the group L-U--V
wherein L, U, and V are independently selected from the group
consisting of O, S, C(O), C(S), C(J.sub.H).sub.2 S(O), SO.sub.2,
OP(OR.sup.31)R.sup.30, P(O)R.sup.30, P(S)R.sup.30,
C(R.sup.30)R.sup.31, C.dbd.C(R.sup.30)R.sup.31,
(O).sub.2POP(O).sub.2, R.sup.30(O)POP(O)R.sup.- 30,
Si(R.sup.29)R.sup.28, Si.sup.29)R.sup.28Si(R.sup.29)R.sup.28,
Si(R.sup.29)R.sup.28OSi(R.sup.29)R.sup.28,
(R.sup.28)R.sup.29COC(R.sup.28- )R.sup.29,
(R.sup.28)R.sup.29CSC(R.sup.28)R.sup.29,
C(O)C(R.sup.30).dbd.C(R.sup.31), C(S)C(R.sup.30).dbd.C(R.sup.31),
S(O)C(R.sup.30).dbd.C(R.sup.31),
SO.sub.2C(R.sup.30).dbd.C(R.sup.31),
PR.sup.30C(R.sup.30).dbd.C(R.sup.31),
P(O)R.sup.30C(R.sup.30).dbd.C(R.sup- .31),
P(S)R.sup.30C(R.sup.30).dbd.C(R.sup.31), DC(R.sup.30)(R.sup.31)D,
OP(OR.sup.31)R.sup.30, P(O)R.sup.30,P(S)R.sup.30,
Si(R.sup.28)R.sup.29 and N(R.sup.30), and a covalent bond with the
proviso that no more than any two of L, U and V are simultaneously
covalent bonds and the heterocyclyl comprised of by L, U, and V has
from 5 through 10 contiguous member; D is selected from the group
consisting of oxygen, C.dbd.O, C.dbd.S, and S(O).sub.m wherein m is
an integer selected from 0 through 2; J.sub.H is independently
selected from the group consisting of OR.sup.27, SR.sup.27 and
N(R.sup.20O)R.sup.21; R.sup.27 is selected from the group
consisting of hydrido, alkyl, alkenyl, alkynyl, aralkyl,
aryloxyalkyl, aralkoxyalkyl, alkylsulfinylalkyl,
alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkylthioalkyl,
alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl,
arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl,
cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl,
halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl,
haloalkenyloxyalkyl, halocycloalkoxyalkyl,
halocycloalkenyloxyalkyl, perhaloaryloxyalkyl, heteroaryl,
heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl,
arylsulfinylalkyl, arylsulfonylalkyl, cycloalkylsulfinylalkyl,
cycloalkylsufonylalkyl, heteroarylsulfonylalkyl,
heteroarylsulfinylalkyl, aralkylsulfinylalkyl and
aralkylsulfonylalkyl; R.sup.28 and R.sup.29 are independently
selected from the group consisting of hydrido, hydroxyalkyl, alkyl,
alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, acyl, aroyl,
aralkanoyl, heteroaroyl, aralkoxyalkyl, alkylsulfinylalkyl,
alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkylthioalkyl,
alkoxyalkyl, heteroarloxyalkyl, alkenyloxyalkyl, alkylthioalkyl,
arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl,
cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl,
halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl,
haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl,
halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl,
perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl,
heteroarylthioalkyl, heteroaralkylthioalkyl, cyanoalkyl,
dicyanoalkyl, carboxamidoalkyl, dicarboxamidoalkyl,
cyanocarboalkoxyalkyl, carboalkoxyalkyl, dicarboalkoxyalkyl,
cyanocycloalkyl, dicyanocycloalkyl, carboxamidocycloalkyl,
dicarboxamidocycloalkyl, carboalkoxycyanocycloalky- l,
carboalkoxycycloalkyl, dicarboalkoxycycloalkyl, formylalkyl,
acylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, aralkylsulfinyl,
cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl,
heteroarylsulfonylalkyl, heteroarylsulfinylalkyl,
aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy,
dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl and
diaralkoxyphosphonoalkyl; R.sup.28 and R.sup.29 are taken together
to form a linear moiety spacer having from 2 through 7 contiguous
atoms and forming a ring selected from the group consisting of a
cycloalkyl ring having from 3 through 8 contiguous members, a
cycloalkenyl ring having from 3 through 8 contiguous members, and a
heterocyclyl ring having from 3 through 8 contiguous members;
R.sup.30 and R.sup.31 are independently selected from hydrido,
hydroxy, thiol, aryloxy, amino, alkylamino, dialkylamino,
hydroxyalkyl, heteroaryloxyalkyl, alkoxy, alkylthio, arylthio,
alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl,
aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl,
aralkylthioalkyl, heteroaralkoxythioalkyl, alkoxyalkyl,
heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl,
cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl,
cycloalkenylalkyl, haloalkyl, haloalkenyl,
haloaralkylsulfinylalkyl, aralkylsulfonylalkyl, cyanoalkyl,
dicyanoalkyl, carboxamidoalkyl, dicarboxamidoalkyl,
cyanocarboalkoxyalkyl, carboalkoxyalkyl, dicarboalkoxyalkyl,
cyanocycloalkyl, dicyanocycloalkyl, carboxamidocycloalkyl,
dicarboxamidocycloalkyl, carboalkoxycyanocycloalkyl,
carboalkoxycycloalkyl, dicarboalkoxycycloalkyl, formylalkyl,
acylalkyl, dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl,
phosphonoalkyl, dialkoxyphosphonoalkoxy, diaralkoxyphosphonoalkoxy,
phosphonoalkoxy, dialkoxyphosphonoalkylamino,
diaralkoxyphosphonoalkylamino, phosphonoalkylamino,
dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl, sulfonylalkyl,
alkoxysulfonylalkyl, aralkoxysulfonylalkyl, alkoxysulfonylalkoxy,
aralkoxysulfonylalkoxy, sulfonylalkoxy, alkoxysulfonylalkylamino,
aralkoxysulfonylalkylamino, and sulfonylalkylamino; R.sup.30 and
R.sup.31 are taken to form a linear moiety spacer group having from
2 through 7 contiguous atoms to form a ring selected from the group
consisting of a cycloalkyl ring having from
3 through 8 contiguous members, a cycloalkenyl ring having from 3
through 8 contiguous members, and a heterocyclyl ring having from 3
through 8 contiguous members; Q.sup.S is selected from the group
consisting of a single covalent bond,
(CR.sup.37R.sup.38).sub.b--(W.sup.0).sub.az wherein az is an
integer selected from 0 through 1, b is an integer selected from 1
through 4, and W.sup.0 is selected from the group consisting of O,
S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.14),
(R.sup.14)NC(O), C(S)N(R.sup.14), (R.sup.14)NC(S),
OC(O)N(R.sup.14), SC(S)N(R.sup.14), SC(O)N(R.sup.14),
OC(S)N(R.sup.14), N(R.sup.15)C(O)N(R.sup.14),
(R.sup.14)NC(O)N(R.sup.15), N(R.sup.15)C(S)N(R.sup.14),
(R.sup.14)NC(S)N(R.sup.15), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, Se, Se(O),
Se(O).sub.2, Se(O).sub.2N(R.sup.17), N(R.sup.14)Se(O).sub.2,
P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7),
N(R.sup.14), ON(R.sup.4), and SiR.sup.28R.sup.29,
(CH(R.sup.14)).sub.c--W.sup.1--(CH(R.sup.15)).sub.d wherein c and d
are integers independently selected from 1 through 4, and W.sup.1
is selected from the group consisting of O, S, C(O), C(S), C(O)O,
C(S)O, C(O)S, C(S)S, C(O)N(R.sup.14), (R.sup.14)NC(O),
C(S)N(R.sup.14), (R.sup.14)NC(S), OC(O)N(R.sup.14),
(R.sup.14)NC(O)O, SC(S)N(R.sup.14), (R.sup.14)NC(S)S,
SC(O)N(R.sup.14), (R.sup.14)NC(O)S, OC(S)N(R.sup.14),
(R.sup.14)NC(S)O, N(R.sup.15)C(O)N(R.sup.14),
(R.sup.14)NC(O)N(R.sup.15), N(R.sup.15)C(S)N(R.sup.14),
(R.sup.14)NC(S)N(R.sup.15), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, Se, Se(O),
Se(O).sub.2, Se(O).sub.2N(R.sup.14), N(R.sup.14)Se(O).sub.2,
P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7),
N(R.sup.14), ON(R.sup.14), SiR.sup.28R.sup.29, and
(CH(R.sup.14)).sub.e--W.sup.2--(CH(- R.sup.15)).sub.h wherein e and
h are integers independently selected from 0 through 2 and W.sup.2
is selected from the group consisting of CR.sup.4a.dbd.CR.sup.4b,
ethynylidene (C.ident.C; 1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b
with the provisos that R.sup.14 and R.sup.15 are selected from
other than halo and cyano when directly bonded to N and that
(CR.sup.37R.sup.38).sub.b, (CH(R.sup.14)).sub.c,
(CH(R.sup.14)).sub.e and are bonded to E.sup.0; Y.sup.0 is
Q.sup.b-Q.sup.ss wherein Q.sup.ss is selected from the group
consisting of (CR.sup.37R.sup.38).sub.f wherein f is an integer
selected from 1 through 6,
(CH(R.sup.14)).sub.c--W.sup.1--(CH(R.sup.15)).sub.d wherein c and d
are integers independently selected from 1 through 4, and W.sup.1
is selected from the group consisting of W.sup.1 is selected from
the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,
C(S)S, C(O)N(R.sup.14), (R.sup.14)NC(O), C(S)N(R.sup.14),
(R.sup.14)NC(S), OC(O)N(R.sup.14), (R.sup.14)NC(O)O,
SC(S)N(R.sup.14), (R.sup.14)NC(S)S, SC(O)N(R.sup.14),
(R.sup.14)NC(O)S, OC(S)N(R.sup.14), (R.sup.14)NC(S)O,
N(R.sup.15)C(O)N(R.sup.14), (R.sup.14)NC(O)N(R.sup.15),
N(R.sup.15)C(S)N(R.sup.14), (R.sup.14)NC(S)N(R.sup.15), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, Se,
Se(O), Se(O).sub.2, Se(O).sub.2N(R.sup.14), N(R.sup.14)Se(O).sub.2,
P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7),
N(R.sup.14), ON(R 14) SiR.sup.28R.sup.29, and
(CH(R.sup.14)).sub.e--W.sup.2--(CH(R.sup.15)).sub- .h wherein e and
h are integers independently selected from 0 through 2 and W.sup.2
is selected from the group consisting of CR.sup.4a.dbd.CR.sup.4b,
ethynylidene (C.ident.C; 1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b
with the provisos that R.sup.14 and R.sup.15 are selected from
other than halo and cyano when directly bonded to N and that
(CR.sup.37R.sup.38).sub.f, (CH(R.sup.15)).sub.c, and
(CH(R.sup.15)).sub.e are bonded to E.sup.0; Y.sup.0 is
Q.sup.b-Q.sup.sss wherein Q.sup.sss is
(CH(R.sup.38)).sub.r--W.sup.3, r is an integer selected from 1
through 3, and W is selected from the group consisting of
1,1-cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl,
1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl,
1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl,
2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 1
,2-piperazinyl, 1 ,3-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl,
2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,
1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl,
2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl,
1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl,
4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl,
2H-pyran-2-one-4,5-yl, 4H-pyran-4-one-2,3-yl,
2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,
2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl,
2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl,
2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl,
3,4-tetrahydropyranyl, and 3,5-tetrahydropyranyl with the proviso
that (CH(R.sup.38)).sub.r is bonded to E.sup.0 and Q.sup.b is
bonded to lowest numbered substituent position of each W.sup.3;
Y.sup.0 is Q.sup.b-Q.sup.sssr wherein Q.sup.sssr is
(CH(R.sup.38)).sub.r--W.sup.4, r is an integer selected from 1
through 3, and W.sup.4 is selected from the group consisting of
1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl,
1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,
2,5-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl,
1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl,
2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,
1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl,
2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl,
1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl,
4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl,
2H-pyran-2-one-4,5-yl, 4H-pyranone-2,3-yl, 2,3-tetrahydrofuranyl,
2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl,
3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,
2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,
2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and
3,5-tetrahydropyranyl with the provisos that (CH(R.sup.38)).sub.r
is bonded to E.sup.0 and Q.sup.b is bonded to highest number
substituent position of each W.sup.4; Y.sup.0 is
Q.sup.b-Q.sup.sssswherein Q.sup.ssss is
(CH(R.sup.38)).sub.r--W.sup.5, r is an integer selected from 1
through 3, and W.sup.5 is selected from the group consisting of
1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl,
2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl,
3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl,
2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,
3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,
2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,
2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,
3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,
2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,
3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,
2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,
1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,
3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,
2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,
3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,
1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl,
1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,
2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,
2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,
3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,
4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,
1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,
1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,
3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,
3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,
4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,
3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,
4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl
with the proviso that Q.sup.b is bonded to lowest number
substituent position of each W.sup.5 and that (CH(R.sup.38)).sub.r
is bonded to E.sup.0; Y.sup.0 is Q.sup.b-Q.sup.ssssr wherein
Q.sup.ssssris (CH(R.sup.38)).sub.r--W.sup.6, r is an integer
selected from 1 through 3, and W.sup.6 is selected from the group
consisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl,
2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl,
3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl,
2,5-benzofuranyl, 2,5-benzofuranyl, 2,7-benzofuranyl,
3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl,
3,7-benzofuranyl, 2,4-benzothiophenyl, 2,5-benzothiophenyl,
2,6-benzothiophenyl, 2,7-benzothiophenyl, 3,4-benzothiophenyl,
3,5-benzothiophenyl, 3,6-benzothiophenyl, 3,7-benzothiophenyl,
2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl,
3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl,
1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl,
2,6-isoindolyl, 2,7-isoindolyl, 1,3-isoindolyl, 3,4-indazolyl,
3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl,
2,4-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl,
3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl,
3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl,
1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl,
2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl,
2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl,
3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl,
3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl,
4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl,
1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl,
3,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl,
3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl,
4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8-isoquinolinyl,
3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl,
3,8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and
4,8-cinnolinyl with the proviso that Q.sup.b is bonded to highest
number substituent position of each W.sup.6 and that
(CH(R.sup.38)).sub.r is bonded to E.sup.0; R.sup.37 and R.sup.38,
when bonded to different carbons, are taken together to form a
linear moiety spacer having from 1 through 7 contiguous atoms to
form a ring selected from the group consisting of a cycloalkyl ring
having from 3 through 8 contiguous members, a cycloalkenyl ring
having from 3 through 8 contiguous members, and a heterocyclyl ring
having from 3 through 8 contiguous members; R.sup.37 and R.sup.38,
when bonded to different carbons, are taken together to form a
linear moiety spacer having from 1 through 7 contiguous atoms to
form a ring selected from the group consisting of a cycloalkyl ring
having from 3 through 8 contiguous members, a cycloalkenyl ring
having from 3 through 8 contiguous members, and a heterocyclyl ring
having from 3 through 8 contiguous members; R.sup.38 and R.sup.38,
when bonded to different carbons, are taken together to form a
linear moiety spacer having from 1 through 7 contiguous atoms to
form a ring selected from the group consisting of a cycloalkyl ring
having from 3 through 8 contiguous members, a cycloalkenyl ring
having from 3 through 8 contiguous members, and a heterocyclyl ring
having from 3 through 8 contiguous members; R.sup.37 and R.sup.38,
when bonded to the same carbon, are taken together to form a group
selected from a group consisting of oxo, thiono, alkylene,
haloalkylene, and a linear moiety spacer having from 2 through 7
contiguous atoms to form a ring selected from the group consisting
of a cycloalkyl ring having from 3 through 8 contiguous members, a
cycloalkenyl ring having from 3 through 8 contiguous members, and a
heterocyclyl ring having from 3 through 8 contiguous members;
R.sup.39 and R.sup.40, when bonded to the same carbon, are taken
together to form a group selected from a group consisting of oxo,
thiono, R.sup.5--N, alkylene, haloalkylene, and a linear moiety
spacer having from 2 through 7 contiguous atoms to form a ring
selected from the group consisting of a cycloalkyl ring having from
3 through 8 contiguous members, a cycloalkenyl ring having from 3
through 8 contiguous members, and a heterocyclyl ring having from 3
through 8 contiguous members.
2. The compound as recited in claim 1 or a pharmaceutically
acceptable salt thereof, wherein; B is formula (V): 82wherein
D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are independently
selected from the group consisting of C, N, O, S and a covalent
bond with the provisos that no more than one is a covalent bond, no
more than one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 is
O, no more than one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and
K.sup.1 is S, one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1
must be a covalent bond when two of D.sup.1, D.sup.2, J.sup.1,
J.sup.2 and K.sup.1 are O and S, and no more than four of D.sup.1,
D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are N with the proviso that
R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are each
independently selected to maintain the tetravalent nature of
carbon, trivalent nature of nitrogen, the divalent nature of
sulfur, and the divalent nature of oxygen; R.sup.32, R.sup.33,
R.sup.34, R.sup.35, and R.sup.36 are independently selected to be
Q.sup.b; R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.16,
R.sup.17, R.sup.18, R.sup.19, R.sup.32, R.sup.33,R.sup.34,
R.sup.35, and R.sup.36 are independently selected from the group
consisting of hydrido, amidino, guanidino, dialkylsulfonium,
trialkylphosphonium, dialkylsulfoniumalkyl, carboxy,
heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl,
acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl,
aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl,
aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl,
aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl,
cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl,
cycloalkylsulfonylalkyl, heteroarylamino,
N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl,
haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl,
heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl,
cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy,
halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy,
halocycloalkenyloxyalkyl, hydroxy, amino, alkoxyamino, thio, nitro,
lower alkylamino, alkylthio, alkylthioalkyl, arylamino,
aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl,
alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl,
arylsulfonylalkyl, heteroarylsulfinylalkyl,
heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl,
haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,
alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl
amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido,
diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl,
arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl,
heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio,
alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl,
heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl,
alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy,
cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower
cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl,
haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl,
hydroxyalkyl, aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl,
aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated
heterocyclyl, partially saturated heterocyclyl, heteroaryl,
heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl,
arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy,
alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido,
carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido,
carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono,
phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl;
R.sup.32 and R.sup.33, R.sup.33 and R.sup.34, R.sup.34 and
R.sup.35, and R.sup.35 and R.sup.36 pairs are independently
selected to form a spacer pair wherein a spacer pair is taken
together to form a linear moiety having from 3 through 6 contiguous
atoms connecting the points of bonding of said spacer pair members
to form a ring selected from the group consisting of a cycloalkenyl
ring having 5 through 8 contiguous members, a partially saturated
heterocyclyl ring having 5 through 8 contiguous members, a
heteroaryl ring having 5 through 6 contiguous members, and an aryl
with the proviso that no more than one of the group consisting of
spacer pairs R.sup.32 and R.sup.33, R.sup.33 and R.sup.34, R.sup.34
and R.sup.35, and R.sup.35 and R.sup.36 is used at the same time; B
is selected from the group consisting of C3-C8 alkyl, C3-C8
alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl
wherein each member of group B may be optionally substituted at any
carbon up to and including 6 atoms from the point of attachment of
B to A with one or more of the group consisting of R.sub.32,
R.sub.33, R.sub.34, R.sub.35, and R.sub.36; B is selected from the
group consisting of C3-C10 cycloalkyl, C5-C10 cycloalkenyl, C4-C9
saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl,
wherein each ring carbon may be optionally substituted with
R.sub.33, a ring carbon other than the ring carbon at the point of
attachment of B to A may be optionally substituted with oxo
provided that no more than one ring carbon is substituted by oxo at
the same time, ring carbon and nitrogen atoms adjacent to the
carbon atom at the point of attachment may be optionally
substituted with R.sub.9 or R.sub.13, a ring carbon or nitrogen
atom adjacent to the R.sub.9 position and two atoms from the point
of attachment may be substituted with R.sub.10, a ring carbon or
nitrogen atom adjacent to the R.sub.13 position and two atoms from
the point of attachment may be substituted with R.sub.12, a ring
carbon or nitrogen atom three atoms from the point of attachment
and adjacent to the R.sub.10 position may be substituted with
R.sub.11, a ring carbon or nitrogen atom three atoms from the point
of attachment and adjacent to the R.sub.12 position may be
substituted with R.sub.33, and a ring carbon or nitrogen atom four
atoms from the point of attachment and adjacent to the R.sub.11 and
R.sub.33 positions may be substituted with R.sub.34; R.sup.9 and
R.sup.10, R.sup.10 and R.sup.11, R.sup.11 and R.sup.12, and
R.sup.12 and R.sup.13 pairs are independently selected to form a
spacer pair wherein a spacer pair is taken together to form a
linear moiety having from 3 through 6 contiguous atoms connecting
the points of bonding of said spacer pair members to form a ring
selected from the group consisting of a cycloalkenyl ring having 5
through 8 contiguous members, a partially saturated heterocyclyl
ring having 5 through 8 contiguous members, a heteroaryl ring
having 5 through 6 contiguous members, and an aryl with the proviso
that no more than one of the group consisting of spacer pairs
R.sup.9 and R.sup.10, R.sup.10 and R.sup.11, R.sup.11 and R.sup.12,
and R.sup.12 and R.sup.13 is used at the same time; A is selected
from the group consisting of single covalent bond,
(W.sup.7).sub.rr--(CH(R.sup.15)- ).sub.pa and
(CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr wherein rr is an integer
selected from 0 through 1, pa is an integer selected from 0 through
6, and W.sup.7 is selected from the group consisting of O, S, C(O),
C(S), C(O)S, C(S)O, C(O)N(R.sup.7), C(S)N(R.sup.7), (R.sup.7)NC(O),
(R.sup.8)NC(S), S(O), S(O).sub.2, S(O).sub.2N(R.sup.7),
(R.sup.7)NS(O).sub.2, P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8),
P(O)(R.sup.8)N(R.sup.7), C(NR.sup.7)N(R.sup.7),
(R.sup.7)NC(NR.sup.7), and N(R.sup.7); R.sup.7 and R.sup.8 are
independently selected from the group consisting of hydrido,
hydroxy, alkyl, acyl, aroyl, heteroaroyl, and alkoxyalkyl;
R.sup.14, R.sup.15, R.sup.37, and R.sup.38 are independently
selected from the group consisting of hydrido, hydroxy, halo,
cyano, hydroxyalkyl, alkoxy, alkyl, alkoxyalkyl, cycloalkyl,
cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl,
haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl,
halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl,
carboxy, carboxyalkyl, carboalkoxy, carboxamide, and
carboxamidoalkyl; .PSI. is selected from the group consisting of
NR.sup.5, O, C(O), C(S), S, S(O), S(O).sub.2, ON(R.sup.5),
P(O)(R.sup.8), and CR.sup.39R.sup.40; R.sup.5 is selected from the
group consisting of hydrido, alkyl, alkoxy, alkoxyalkyl, haloalkyl,
acyl, aroyl, and heteroaroyl; R.sup.39 and R.sup.40 are
independently selected from the group consisting of hydrido,
hydroxy, halo, cyano, hydroxyalkyl, acyl, aroyl, heteroaroyl,
acylamido, alkoxy, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy,
haloalkoxyalkyl, alkylsulfonyl, haloalkylsulfonyl, carboxy,
carboxyalkyl, carboalkoxy, carboxamide, and carboxamidoalkyl;
X.sup.0 and R.sup.2 are independently selected from the group
consisting of Z.sup.0-Q, hydrido, alkyl, alkenyl, and halo; X.sup.0
and R.sup.2 are independently selected from the group consisting of
amidino, guanidino, dialkylsulfonium, trialkylphosphonium,
dialkylsulfoniumalkyl, heteroarylamino, amino, nitro, alkylamino,
arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl,
aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl,
cyano, and phosphono; Z.sup.0 is selected from the group consisting
of covalent single bond, (CR.sup.41R.sup.42).sub.q wherein q is an
integer selected from 1 through 6,
(CH(R.sup.41)).sub.g--W.sup.0--(CH(R.sup.42)).sub.p wherein g and p
are integers independently selected from 0 through 3 and W.sup.0 is
selected from the group consisting of O, S, C(O), C(S), C(O)O,
C(S)O, C(O)S, C(S)S, C(O)N(R.sup.41), (R.sup.41)NC(O),
C(S)N(R.sup.41), (R.sup.41)NC(S), OC(O)N(R.sup.41),
(R.sup.41)NC(O)O, SC(S)N(R.sup.41), (R.sup.41)NC(S)S,
SC(O)N(R.sup.41), (R.sup.41)NC(O)S, OC(S)N(R.sup.41),
(R.sup.41)NC(S)O, N(R.sup.42)C(O)N(R.sup.42),
(R.sup.41)NC(O)N(R.sup.42), N(R.sup.42)C(S)N(R.sup.41),
(R.sup.41)NC(S)N(R.sup.42), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.41), N(R.sup.41)S(O).sub.2, P(O)(R.sup.8),
N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7), N(R.sup.41),
ON(R.sup.41), and
(CH(R.sup.41)).sub.e--W.sup.2--(CH(R.sup.42)).sub.h wherein e and h
are integers independently selected from 0 through 2 and W.sup.2 is
selected from the group consisting of CR.sup.41.dbd.CR.sup.42,
CR.sup.41R.sup.42.dbd.C; vinylidene), and ethynylidene (C.ident.C;
1,2-ethynyl), with the provisos that R.sup.41 and R.sup.42 are
selected from other than halo and cyano when directly bonded to N
and Z.sup.0 is directly bonded to the quinone ring; R.sup.41 and
R.sup.42 are independently selected from the group consisting of
hydrido, hydroxy, halo, cyano, aryloxy, hydroxyalkyl, acyl, aroyl,
heteroaroyl, heteroaryloxyalkyl, alkoxy, alkyl, aryl, aralkyl,
aryloxyalkyl, aralkoxyalkylalkoxy, alkoxyalkyl, heteroaryloxyalkyl,
cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl,
cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl,
halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl,
halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl,
saturated heterocyclyl, partially saturated heterocyclyl,
heteroaryl, heteroaralkyl, heteroarylthioalkyl,
heteroaralkylthioalkyl, alkylsulfonyl, haloalkylsulfonyl,
arylsulfonyl, arylsulfonylalkyl, aralkylsulfonyl,
cycloalkylsulfonyl, cycloalkylsufonylalkyl,
heteroarylsulfonylalkyl, heteroarylsulfonyl, and
aralkylsulfonylalkyl; Q is formula (II): 83wherein D.sup.1,
D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are independently selected
from the group consisting of C, N, O, S and a covalent bond with
the provisos that no more than one is a covalent bond, no more than
one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 is O, no more
than one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 is S,
one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 must be a
covalent bond when two of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and
K.sup.1 are O and S, and no more than four of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 are N, with the proviso that R.sup.9,
R.sup.10, R.sup.11, R.sup.12, and R.sup.13 are each independently
selected to maintain the tetravalent nature of carbon, trivalent
nature of nitrogen, the divalent nature of sulfur, and the divalent
nature of oxygen; Q is formula (III): 84wherein D.sup.3, D.sup.4,
J.sup.3, and J.sup.4 are independently selected from the group
consisting of C, N, O, and S, no more than one of D.sup.3, D.sup.4,
J.sup.3, and J.sup.4 is O, no more than one of D.sup.3, D.sup.4,
J.sup.3, and J.sup.4 is S, and no more than three of D.sup.1,
D.sup.2, J.sup.1, and J.sup.2 are N with the proviso that R.sup.9,
R.sup.10, R.sup.11, and R.sup.12 are each independently selected to
maintain the tetravalent nature of carbon, trivalent nature of
nitrogen, the divalent nature of sulfur, and the divalent nature of
oxygen; Q is selected from the group consisting of alkyl, alkoxy,
alkylamino, alkylthio, haloalkylthio, alkenyl, alkynyl, saturated
heterocyclyl, partially saturated heterocyclyl, acyl, aroyl,
heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl,
cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy,
haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl,
haloalkenyloxyalkyl, halocycloalkoxyalkyl, and
halocycloalkenyloxyalkyl; K is (CR.sup.4aR.sup.4b).sub.n wherein n
is an integer selected from 1 through 2; R.sup.4a and R.sup.4b are
independently selected from the group consisting of halo, hydrido,
hydroxy, cyano, hydroxyalkyl, alkyl, alkenyl, alkoxyalkyl,
haloalkyl, haloalkenyl, and cyanoalkyl; R.sup.4a and R.sup.4b, when
bonded to the same carbon, are taken together to form a group
selected from the group consisting of oxo, and a linear spacer
moiety having from 2 through 7 contiguous atoms connected to form a
ring selected from the group consisting of a cycloalkyl ring having
3 through 8 contiguous members, a cycloalkenyl ring having 5
through 8 contiguous members, and a heterocyclyl ring having 5
through 8 contiguous members; E.sup.0 is E.sup.1, when K is
(CR.sup.4aR.sup.4b).sub.n, wherein E.sup.1 is selected from the
group consisting of a covalent single bond, O, S, C(O), C(S),
C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.7), (R.sup.7)NC(O),
C(S)N(R.sup.7), (R.sup.7)NC(S), OC(O)N(R.sup.7), (R.sup.7)NC(O)O,
SC(S)N(R.sup.7), (R.sup.7)NC(S)S, SC(O)N(R.sup.7), (R.sup.7)NC(O)S,
OC(S)N(R.sup.7), (R.sup.7)NC(S)O, N(R.sup.8)C(O)N(R.sup.7),
(R.sup.7)NC(O)N(R.sup.8), N(R.sup.8)C(S)N(R.sup.7),
(R.sup.7)NC(S)N(R.sup.8), S(O), S(O).sub.2, S(O).sub.2N(R.sup.7),
N(R.sup.7)S(O).sub.2, S(O).sub.2N(R.sup.7)C( O),
C(O)N(R.sup.7)S(O).sub.2- , P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8),
P(O)(R.sup.8)N(R.sup.7), N(R.sup.7), ON(R.sup.7),
CR.sup.4a.dbd.CR.sup.4b, ethynylidene (C.ident.C; 1,2-ethynyl), and
C.dbd.CR.sup.4aR.sup.4b; K is (CH(R.sup.14)).sub.j-T wherein j is
selected from a integer from 0 through 2 and T is selected from the
group consisting of single covalent bond, O, S, and N(R.sup.7) with
the proviso that (CH(R.sup.14)).sub.j is bonded to the quinone
ring; E.sup.0 is E.sup.2, when K is (CH(R.sup.14)).sub.j-T, wherein
E.sup.2 is selected from the group consisting of a covalent single
bond, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.7),
(R.sup.7)NC(O), C(S)N(R.sup.7), (R.sup.7)NC(S), (R.sup.7)NC(O)O,
(R.sup.7)NC(S)S, (R.sup.7)NC(O)S, (R.sup.7)NC(S)O,
N(R.sup.8)C(O)N(R.sup.7), (R.sup.7)NC(O)N(R.sup.8),
N(R.sup.8)C(S)N(R.sup.7), (R.sup.7)NC(S)N(R.sup.8), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.7), N(R.sup.7)S(O).sub.2,
S(O).sub.2N(H)C(O), C(O)N(H)S(O).sub.2, P(O)(R.sup.8),
N(R.sup.7)P(O)(R.sup.7), P(O)(R.sup.8)N(R.sup.7), and N(R.sup.7); K
is G-(CH(R.sup.15)).sub.k wherein k is selected from an integer
from 1 through 2 and G is selected from the group consisting of O,
S, and N(R.sup.7) with the proviso that R.sup.15 is other than
hydroxy, cyano, halo, amino, alkylamino, dialkylamino, and
sulfhydryl when k is 1; E.sup.0 is E.sup.3, when K is
G-(CH(R.sup.15)).sub.k, wherein E.sup.3 is selected from the group
consisting of a covalent single bond, O, S, C(O), C(S), C(O)O,
C(S)O, C(O)S, C(S)S, C(O)N(R.sup.7), (R.sup.7)NC(O),
C(S)N(R.sup.7), (R.sup.7)NC(S), OC(O)N(R.sup.7), (R.sup.7)NC(O)O,
SC(S)N(R.sup.7), (R.sup.7)NC(S)S, SC(O)N(R.sup.7), (R.sup.7)NC(O)S,
OC(S)N(R.sup.7), (R.sup.7)NC(S)O, N(R.sup.8)C(O)N(R.sup.7),
(R.sup.7)NC(O)N(R.sup.8), N(R.sup.8)C(S)N(R.sup.7),
(R.sup.7)NC(S)N(R.sup.8), S(O), S(O).sub.2, S(O).sub.2N(R.sup.7),
N(R.sup.7)S(O).sub.2, P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8),
P(O)(R.sup.8)N(R.sup.7), N(R.sup.7), ON(R.sup.7),
CR.sup.4a.dbd.CR.sup.4b, ethynylidene (C.ident.C; 1,2-ethynyl), and
C.dbd.CR.sup.4aR.sup.4b; Y.sup.0 is formula (IV): 85wherein
D.sup.5, D.sup.6, J.sup.5, and J.sup.6 are independently selected
from the group consisting of C, N, O, S and a covalent bond with
the provisos that no more than one is a covalent bond, K.sup.2 is
independently selected from the group consisting of C, and N.sup.+,
no more than one of D.sup.5, D.sup.6, J.sup.5, and J.sup.6 is O, no
more than one of D.sup.5, D.sup.6, J.sup.5, and J.sup.6 is S, one
of D.sup.5, D.sup.6, J.sup.5, and J.sup.6 must be a covalent bond
when two of D.sup.5, D.sup.6, J.sup.5, and J.sup.6 are O and S, no
more than three of D.sup.5, D.sup.6, J.sup.5, and J.sup.6 are N
when K.sup.2 is N.sup.+, and no more than four of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 are N when K
is carbon with the provisos that R.sup.16, R.sup.17, R.sup.18, and
R.sup.19 are each independently selected to maintain the
tetravalent nature of carbon, trivalent nature of nitrogen, the
divalent nature of sulfur, and the divalent nature of oxygen;
R.sup.16 and R.sup.17 are taken together to form a linear moiety
spacer having from 3 through 6 contiguous atoms connected to form a
ring selected from the group consisting of a cycloalkenyl ring
having from 5 through 8 contiguous members, a partially saturated
heterocyclyl ring having from 5 through 8 contiguous members, a
heteroaryl having from 5 through 6 contiguous members, and an aryl;
Q.sup.b is selected from the group consisting of NR.sup.20R.sup.21,
NR.sup.20R.sup.21R.sup.22, oxy, alkyl, alkylaminoalkyl, aminoalkyl,
dialkylsulfoniumalkyl, and acylamino wherein R.sup.20, R.sup.21 ,
and R.sup.22 are independently selected from the group consisting
of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino,
aminoalkyl, and hydroxyalkyl with the provisos that no more than
one of R.sup.20, R.sup.21, and R.sup.22 is hydroxy, alkoxy,
alkylamino, amino, and dialkylamino and that R.sup.20, R.sup.21,
and R.sup.22 must be other than be hydroxy, alkoxy, alkylamino,
amino, and dialkylamino when K.sup.2 is N.sup.+; R.sup.20 and
R.sup.21, R.sup.20 and R.sup.22, and R.sup.21 and R.sup.22 pairs
are independently selected to form a spacer pair wherein a spacer
pair is taken together to form a linear moiety having from 4
through 7 contiguous atoms connecting the points of bonding of said
spacer pair members to form a heterocyclyl ring having 5 through 8
contiguous members with the proviso that no more than one of the
group consisting of spacer pairs R.sup.20 and R.sup.21, R.sup.20
and R.sup.22, and R.sup.21 and R.sup.22 is used at the same time;
Q.sup.b is selected from the group consisting of
N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24), N(R.sup.26)C(O)OR.sup.5,
N(R.sup.26)C(O)SR.sup.5, N(R.sup.26)C(S)OR.sup.5 and
N(R.sup.26)C(S)SR.sup.5 with the proviso that no more than one of
R.sup.23, R.sup.24, and R.sup.26 is hydroxy, alkoxy, alkylamino,
amino, or dialkylamino when two of the group consisting of
R.sup.23, R.sup.24, and R.sup.26 are bonded to the same atom;
Q.sup.b is selected from the group consisting of dialkylsulfonium,
trialkylphosphonium, C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.2- 4),
N(R.sup.26)C(O)N(R.sup.23)(R.sup.24),
N(R.sup.26)C(S)N(R.sup.23)(R.sup- .24), C(NR.sup.25)OR.sup.5,
C(O)(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24- ),
C(S)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24),
C(NR.sup.25)SR.sup.5, C(O)NR.sup.23R.sup.24, and
C(O)NR.sup.23R.sup.24 with the provisos that no more than one of
R.sup.23, R.sup.24, and R.sup.26 is hydroxy, alkoxy, alkylamino,
amino, or dialkylamino when two of the group consisting of
R.sup.23, R.sup.24, and R.sup.26 are bonded to the same atom and
that said Q.sup.b group is bonded directly to a carbon atom;
R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, alkyl, hydroxy,
alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl;
R.sup.23 and R.sup.24 are taken together to form a linear spacer
moiety having from 4 through 7 contiguous atoms connecting the
points of bonding to form a heterocyclyl ring having 5 through 8
contiguous members; Q.sup.s is selected from the group consisting
of a single covalent bond,
(CR.sup.37R.sup.38).sub.b--(W.sup.0).sub.az wherein az is an
integer selected from 0 through 1, b is an integer selected from 1
through 4, and W.sup.0 is selected from the group consisting of O,
S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.14),
(R.sup.14)NC(O), C(S)N(R.sup.14), (R.sup.14)NC(S),
OC(O)N(R.sup.14), SC(S)N(R.sup.14), SC(O)N(R.sup.14),
OC(S)N(R.sup.14),
N(R.sup.15)C(O)N(R.sup.14)(R.sup.14)NC(S)N(R.sup.15),
N(R.sup.15)C(S)N(R.sup.14), (R.sup.14)NC(S)N(R.sup.15), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2,
P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7),
N(R.sup.14), ON(R.sup.14),
(CH(R.sup.14)).sub.c--W.sup.1--(CH(R.sup.15)).sub.d wherein c and d
are integers independently selected from 1 through 4, and W.sup.1
is selected from the group consisting of O, S, C(O), C(S), C(O)O,
C(S)O, C(O)S, C(S)S, C(O)N(R.sup.14), (R.sup.14)NC(O),
C(S)N(R.sup.14), (R.sup.14)NC(S), OC(O)N(R.sup.14),
(R.sup.14)NC(O)O, SC(S)N(R.sup.14), (R.sup.14)NC(S)S,
SC(O)N(R.sup.14), (R.sup.14)NC(O)S, OC(S)N(R.sup.14),
(R.sup.14)NC(S)O, N(R.sup.15)C(O)N(R.sup.14),
(R.sup.14)NC(O)N(R.sup.15), N(R.sup.15)C(S)N(R.sup.14),
(R.sup.14)NC(S)N(R.sup.14), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, P(O)(R.sup.8),
N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7), N(R.sup.14),
ON(R.sup.14), and (CH(R.sup.14)).sub.e--W--(CH(R.sup.15)).sub.h
wherein e and h are integers independently selected from 0 through
2 and W.sup.2 is selected from the group consisting of
CR.sup.4a.dbd.CR.sup.4b, ethynylidene (C.dbd.C; 1,2-ethynyl), and
C.dbd.CR.sup.4aR.sup.4b with the provisos that R.sup.14 and
R.sup.15 are selected from other than halo and cyano when directly
bonded to N and that (CR.sup.37R.sup.38).sub.b,
(CH(R.sup.14)).sub.c, (CH(R.sup.14)).sub.e and are bonded to
E.sup.0; Y.sup.0 is Q.sup.b-Q.sup.ss wherein Q.sup.ss is selected
from the group consisting of (CR.sup.37R.sup.38).sub.f wherein f is
an integer selected from 1 through 6,
(CH(R.sup.14)).sub.c--W--(CH(R.sup.15)).sub.d wherein c and d are
integers independently selected from 1 through 4, and W.sup.1 is
selected from the group consisting of W.sup.1 is selected from the
group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,
C(O)N(R.sup.14), (R.sup.14)NC(O), C(S)N(R.sup.14), (R.sup.14)NC(S),
OC(O)N(R.sup.14), (R.sup.14)NC(O)O, SC(S)N(R.sup.14),
(R.sup.14)NC(S)S, SC(O)N(R.sup.14), (R.sup.14)NC(O)S,
OC(S)N(R.sup.14), (R.sup.14)NC(S)O, N(R.sup.15)C(O)N(R.sup.14),
(R.sup.14)NC(O)N(R.sup.15), N(R.sup.15)C(S)N(R.sup.14),
(R.sup.14)NC(S)N(R.sup.15), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, P(O)(R.sup.8),
N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7), N(R.sup.14),
ON(R.sup.14), and (CH(R.sup.14)).sub.e--W--(CH(R.sup.15)).sub.h
wherein e and h are integers independently selected from 0 through
2 and W.sup.2 is selected from the group consisting of
CR.sup.4a.dbd.CR.sup.4b, ethynylidene (C.ident.C; 1,2-ethynyl), and
C.dbd.CR.sup.4aR.sup.4b with the provisos that R.sup.14 and
R.sup.15 are selected from other than halo and cyano when directly
bonded to N and that (CR.sup.37R.sup.38).sub.f,
(CH(R.sup.15)).sub.c, and (CH(R.sup.15)).sub.e are bonded to
E.sup.0; Y.sup.0 is Q.sup.b-Q.sup.sss, wherein Q.sup.sss is
(CH(R.sup.38)).sub.r--W.sup.3, r is an integer selected from 1
through 3, and W is selected from the group consisting of
1,1-cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl,
1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl,
1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl,
2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl,
1,3-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl,
2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl,
2,3-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl,
3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl,
1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl,
4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl,
2H-pyran-2-one4,5-yl, 4H-pyran-4one-2,3-yl, 2,3-tetrahydrofuranyl,
2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl,
3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,
2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,
2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and
3,5-tetrahydropyranyl with the proviso that (CH(R.sup.38)).sub.r is
bonded to E.sup.0 and Q.sup.b is bonded to lowest numbered
substituent position of each W.sup.3; Y.sup.0 is Q.sup.b-Q.sup.sssr
wherein Q.sup.sssr is (CH(R.sup.38)).sub.r--W.sup.4, r is an
integer selected from 1 through 3, and W is selected from the group
consisting of 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl,
1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,
2,4-morpholinyl, 2,5-morpholinyl, 2,5-morpholinyl, 3,4-morpholinyl,
3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl,
2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl,
1,3-piperidinyl, 1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,
2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl,
3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl,
2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl,
3,4-pyrrolidinyl, 2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl,
4H-2,3-pyranyl, 4H-2,4-pyranyl, 4H-2,5-pyranyl,
2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5-yl, 4H-pyran4one-2,3-yl,
2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,
2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl,
2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl,
2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl,
3,4-tetrahydropyranyl, and 3,5-tetrahydropyranyl with the provisos
that (CH(R.sup.38)).sub.r is bonded to E.sup.0 and Q.sup.b is
bonded to highest number substituent position of each W.sup.4;
Y.sup.0 is Q.sup.b-Q.sup.ssss, wherein Q.sup.ssss is
(CH(R.sup.38)).sub.r--W.sup.5, r is an integer selected from 1
through 3, and W is selected from the group consisting of
1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl,
2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl,
3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl,
2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,
3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,
2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,
2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,
3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,
2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,
3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,
2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,
1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,
3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,
2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,
3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,
1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl,
1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,
2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,
2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,
3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,
4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,
1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,
1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,
3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,
3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,
4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,
3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,
4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl
with the proviso that Q.sup.b is bonded to lowest number
substituent position of each W.sup.5 and that (CH(R.sup.38)).sub.r
is bonded to E.sup.0; Y.sup.0 is Q.sup.b-Q.sup.ssssr, wherein
Q.sup.ssssr is (CH(R.sup.38)).sub.r--W.sup.6- , r is an integer
selected from 1 through 3, and W.sup.6 is selected from the group
consisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl,
2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl,
3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl,
2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl,
3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl,
3,7-benzofuranyl, 2,4-benzothiophenyl, 2,5-benzothiophenyl,
2,6-benzothiophenyl, 2,7-benzothiophenyl, 3,4-benzothiophenyl,
3,5-benzothiophenyl, 3,6-benzothiophenyl, 3,7-benzothiophenyl,
2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl,
3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl,
1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl,
2,6-isoindolyl, 2,7-isoindolyl, 1,3-isoindolyl, 3,4-indazolyl,
3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl,
2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl,
3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl,
3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl,
1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl,
2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl,
2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl,
3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl,
3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl,
4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl,
1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl,
3,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl,
3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl,
4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8-isoquinolinyl,
3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl,
3,8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and
4,8-cinnolinyl with the proviso that Q.sup.b is bonded to highest
number substituent position of each W.sup.6 and that
(CH(R.sup.38)).sub.r is bonded to E.sup.0.
3. The compound as recited in claim 1 or a pharmaceutically
acceptable salt thereof, wherein; B is formula (V): 86wherein
D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are independently
selected from the group consisting of C, N, O, S and a covalent
bond with the provisos that no more than one is a covalent bond, no
more than one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 is
O, no more than one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and
K.sup.1 is S, one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1
must be a covalent bond when two of D.sup.1, D.sup.2, J.sup.1,
J.sup.2 and K.sup.1 are O and S, and no more than four of D.sup.1,
D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are N; R.sup.32, R.sup.33,
R.sup.34, R.sup.35, and R.sup.36are independently selected to be
Q.sup.b; R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.16,
R.sup.17, R.sup.18, R.sup.19, R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36 are independently selected from the group
consisting of hydrido, amidino, guanidino, dialkylsulfonium,
trialkylphosphonium, dialkylsulfoniumalkyl, carboxy,
heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl,
acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl,
aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl,
aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl,
aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl,
cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl,
cycloalkylsulfonylalkyl, heteroarylamino,
N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl,
haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl,
heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl,
cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy,
halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy,
halocycloalkenyloxyalkyl, hydroxy, amino, alkoxyamino, thio, nitro,
lower alkylamino, alkylthio, alkylthioalkyl, arylamino,
aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl,
alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl,
arylsulfonylalkyl, heteroarylsulfinylalkyl,
heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl,
haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,
alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl
amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido,
diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl,
arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl,
heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio,
alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl,
heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl,
alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy,
cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower
cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl,
haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl,
hydroxyalkyl, aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl,
aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated
heterocyclyl, partially saturated heterocyclyl, heteroaryl,
heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl,
arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy,
alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido,
carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido,
carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono,
phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl;
B is selected from the group consisting of C3-C8 alkyl, C3-C8
alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl
wherein each member of group B may be optionally substituted at any
carbon up to and including 6 atoms from the point of attachment of
B to A with one or more of the group consisting of R.sub.32,
R.sub.33, R.sub.34, R.sub.35, and R.sub.36; B is selected from the
group consisting of C3-C10 cycloalkyl, C5-C10 cycloalkenyl, C4-C9
saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl,
wherein each ring carbon may be optionally substituted with
R.sub.33, a ring carbon other than the ring carbon at the point of
attachment of B to A may be optionally substituted with oxo
provided that no more than one ring carbon is substituted by oxo at
the same time, ring carbon and nitrogen atoms adjacent to the
carbon atom at the point of attachment may be optionally
substituted with R.sub.9 or R.sub.13, a ring carbon or nitrogen
atom adjacent to the R.sub.9 position and two atoms from the point
of attachment may be substituted with R.sub.10, a ring carbon or
nitrogen atom adjacent to the R.sub.13 position and two atoms from
the point of attachment may be substituted with R.sub.12, a ring
carbon or nitrogen atom three atoms from the point of attachment
and adjacent to the R.sub.10 position may be substituted with
R.sub.11, a ring carbon or nitrogen atom three atoms from the point
of attachment and adjacent to the R.sub.12 position may be
substituted with R.sub.33, and a ring carbon or nitrogen atom four
atoms from the point of attachment and adjacent to the R.sub.11 and
R.sub.33 positions may be substituted with R.sub.34; A is selected
from the group consisting of single covalent bond,
(W.sup.7).sub.rr--(CH(R.sup.15)).sub.pa and
(CH(R.sup.15)).sub.pa--(W.sup- .7).sub.rr wherein rr is an integer
selected from 0 through 1, pa is an integer selected from 0 through
6, and W.sup.7 is selected from the group consisting of O, S, C(O),
C(S), C(O)S, C(S)O, C(O)N(R.sup.7), C(S)N(R.sup.7), (R.sup.7)NC(O),
(R.sup.7)NC(S), S(O), S(O).sub.2, S(O).sub.2N(R.sup.7),
(R.sup.7)NS(O).sub.2, C(NR.sup.7)N(R.sup.7), (R.sup.7)NC(NR.sup.7),
and N(R.sup.7); R.sup.7 and R.sup.8 are independently selected from
the group consisting of hydrido, hydroxy, alkyl, and alkoxyalkyl;
R.sup.14, R.sup.15, R.sup.37, and R.sup.38 are independently
selected from the group consisting of hydrido, hydroxy, halo,
alkyl, alkoxyalkyl, haloalkyl, haloalkoxy, and haloalkoxyalkyl;
.PSI. is selected from the group consisting of NR.sup.5, O, C(O),
C(S), S, S(O), S(O).sub.2, and CR.sup.39R.sup.40; R.sup.5 is
selected from the group consisting of hydrido, alkyl, and alkoxy;
R.sup.39 and R.sup.40 are independently selected from the group
consisting of hydrido, hydroxy, halo, hydroxyalkyl, alkyl,
alkoxyalkyl, haloalkyl, haloalkoxy, and haloalkoxyalkyl; X.sup.0
and R.sup.2 are independently selected from the group consisting of
Z.sup.0-Q, hydrido, alkyl, alkenyl, and halo; X.sup.0 and R.sup.2
are independently selected from the group consisting of amidino,
guanidino, dialkylsulfonium, trialkylphosphonium,
dialkylsulfoniumalkyl, heteroarylamino, amino, nitro, alkylamino,
arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl,
aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl,
cyano, and phosphono; Z.sup.0 is selected from the group consisting
of covalent single bond, (CR.sup.41R.sup.42).sub.q wherein q is an
integer selected from 1 through 2,
(CH(R.sup.41)).sub.g--W.sup.0--(CH(R.sup.42)).sub.p wherein g and p
are integers independently selected from 0 through 2 and W.sup.0 is
selected from the group consisting of O, S, C(O), C(S), C(O)O,
C(S)O, C(O)S, C(S)S, C(O)N(R.sup.41), (R.sup.41)NC(O),
C(S)N(R.sup.41), (R.sup.41)NC(S), OC(O)N(R.sup.41),
(R.sup.41)NC(O)O, SC(S)N(R.sup.41), (R.sup.41)NC(S)S,
SC(O)N(R.sup.41), (R.sup.41)NC(O)S, OC(S)N(R.sup.41),
(R.sup.41)NC(S)O, N(R.sup.42)C(O)N(R.sup.41),
(R.sup.41)NC(O)N(R.sup.42), N(R.sup.42)C(S)N(R.sup.41),
(R.sup.41)NC(S)N(R.sup.42), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.41), N(R.sup.41)S(O).sub.2, N(R.sup.41),
ON(R.sup.41), and
(CH(R.sup.41)).sub.e--W.sup.2--(CH(R.sup.42)).sub.h wherein e and h
are integers independently selected from 0 through 2 and W.sup.2 is
selected from the group consisting of CR.sup.41.dbd.CR.sup.42,
CR.sup.41R.sup.42.dbd.C; vinylidene), and ethynylidene (C.ident.C;
1,2-ethynyl), with the provisos that R.sup.41 and R.sup.42 are
selected from other than halo and cyano when directly bonded to N
and Z.sup.0 is directly bonded to the quinone ring; R.sup.41 and
R.sup.42 are independently selected from the group consisting of
hydrido, hydroxy, halo, cyano, aryloxy, hydroxyalkyl, acyl, aroyl,
heteroaroyl, heteroaryloxyalkyl, alkoxy, alkyl, aryl, aralkyl,
aryloxyalkyl, aralkoxyalkylalkoxy, alkoxyalkyl, heteroaryloxyalkyl,
cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl,
cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl,
halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl,
halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl,
saturated heterocyclyl, partially saturated heterocyclyl,
heteroaryl, and heteroaralkyl; Q is formula (II): 87wherein
D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are independently
selected from the group consisting of C, N, O, S and a covalent
bond with the provisos that no more than one is a covalent bond, no
more than one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 is
O, no more than one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and
K.sup.1 is S, one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1
must be a covalent bond when two of D.sup.1, D.sup.2, J.sup.1,
J.sup.2 and K are O and S, and no more than four of D.sup.1,
D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are N, with the proviso that
R.sup.9, R.sup.10, R.sup.11, R.sup.12, and R.sup.13 are each
independently selected to maintain the tetravalent nature of
carbon, trivalent nature of nitrogen, the divalent nature of
sulfur, and the divalent nature of oxygen; Q is selected from the
group consisting of alkyl, alkoxy, alkylamino, alkylthio,
haloalkylthio, saturated heterocyclyl, alkyl, partially saturated
heterocyclyl, acyl, aroyl, heteroaroyl, cycloalkyl,
cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl,
cycloalkylalkenyl, haloalkyl, haloalkoxy, haloalkenyl,
halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl,
haloalkenyloxyalkyl, halocycloalkoxyalkyl, and
halocycloalkenyloxyalkyl; K is (CR.sup.4aR.sup.4b).sub.n wherein n
is the integer 1; R.sup.4a and R.sup.4b are independently selected
from the group consisting of halo, hydrido, hydroxy, hydroxyalkyl,
alkyl, alkoxyalkyl, and haloalkyl; E.sup.0 is E.sup.1, when K is
(CR.sup.4aR.sup.4b).sub.n, wherein E.sup.1 is selected from the
group consisting of a covalent single bond, O, S, C(O), C(S),
C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.7), (R.sup.7)NC(O),
C(S)N(R.sup.7), (R.sup.7)NC(S), OC(O)N(R.sup.7), (R.sup.7)NC(O)O,
SC(S)N(R.sup.7), (R.sup.7)NC(S)S, SC(O)N(R.sup.7), (R.sup.7)NC(O)S,
OC(S)N(R.sup.7), (R.sup.7)NC(S)O, N(R.sup.8)C(O)N(R.sup.7),
(R.sup.7)NC(O)N(R.sup.8), N(R.sup.8)C(S)N(R.sup.7),
(R.sup.7)NC(S)N(R.sup.8), S(O), S(O).sub.2, S(O).sub.2N(R.sup.7),
N(R.sup.7)S(O).sub.2, S(O).sub.2N(R.sup.7)C(O),
C(O)N(R.sup.7)S(O).sub.2, N(R.sup.7), ON(R.sup.7),
CR.sup.4a.dbd.CR.sup.4b, ethynylidene (C.ident.C; 1,2-ethynyl), and
C.dbd.CR.sup.4aR.sup.4b; K is (CH(R.sup.14)).sub.j-T wherein j is
selected from a integer from 0 through 1 and T is selected from the
group consisting of single covalent bond, O, S, and N(R.sup.7) with
the proviso that (CH(R.sup.14)).sub.j is bonded to the quinone
ring; E.sup.0 is E.sup.2, when K is (CH(R.sup.14)).sub.j-T, wherein
E.sup.2 is selected from the group consisting of a covalent single
bond, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.7),
(R.sup.7)NC(O), C(S)N(R.sup.7), (R.sup.7)NC(S), (R.sup.7)NC(O)O,
(R.sup.7)NC(S)S, (R.sup.7)NC(O)S, (R.sup.7)NC(S)O,
N(R.sup.7)C(O)N(R.sup.7), (R.sup.7)NC(O)N(R.sup.8),
N(R.sup.8)C(S)N(R.sup.7), (R.sup.7)NC(S)N(R.sup.8), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.7), N(R.sup.7)S(O).sub.2,
S(O).sub.2N(H)C(O), C(O)N(H)S(O).sub.2, and N(R.sup.7); K is
G-(CH(R.sup.15)).sub.k wherein k is the integer 1 and G is selected
from the group consisting of O, S, and N(R.sup.7); E.sup.0 is
E.sup.3, when K is G-(CH(R.sup.15)).sub.k, wherein E.sup.3 is
selected from the group consisting of a covalent single bond, O, S,
C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.7),
(R.sup.7)NC(O), C(S)N(R.sup.7), (R.sup.7)NC(S), OC(O)N(R.sup.7),
(R.sup.7)NC(O)O, SC(S)N(R.sup.7), (R.sup.7)NC(S)S, SC(O)N(R.sup.7),
(R.sup.7)NC(O)S, OC(S)N(R.sup.7), (R.sup.7)NC(S)O,
N(R.sup.8)C(O)N(R.sup.7), (R.sup.7)NC(O)N(R.sup.8),
N(R.sup.8)C(S)N(R.sup.7), (R.sup.7)NC(S)N(R.sup.8), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.7), N(R.sup.7)S(O).sub.2, N(R.sup.7),
ON(R.sup.7), CR.sup.4a.dbd.CR.sup.4b, ethynylidene (C.dbd.C;
1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b; Y.sup.0 is formula (IV):
88wherein D.sup.5, D.sup.6, J.sup.5, and J.sup.6 are independently
selected from the group consisting of C, N, O, S and a covalent
bond with the provisos that no more than one is a covalent bond,
K.sup.2 is independently selected from the group consisting of C
and N.sup.+, no more than one of D.sup.5, D.sup.6, J.sup.5, and
J.sup.6 is O, no more than one of D.sup.5, D.sup.6, J.sup.5, and
J.sup.6is S, one of D.sup.5, D.sup.6, J.sup.5, and J.sup.6 must be
a covalent bond when two of D.sup.5, D.sup.6, J.sup.5, and J.sup.6
are O and S, no more than three of D.sup.5, D.sup.6, J.sup.5, and
J.sup.6 are N when K.sup.2 is N.sup.+, and no more than four of
D.sup.5, D.sup.6, J.sup.5, and J.sup.6 are N when K.sup.2 is carbon
with the provisos that R.sup.16, R.sup.17, R.sup.18, and R.sup.19
are each independently selected to maintain the tetravalent nature
of carbon, trivalent nature of nitrogen, the divalent nature of
sulfur, and the divalent nature of oxygen; Q.sup.b is selected from
the group consisting of NR.sup.20R.sup.21,
.sup.+NR.sup.20R.sup.21R.sup.22, oxy, alkyl, alkylaminoalkyl,
aminoalkyl, dialkylsulfoniumalkyl, and acylamino wherein R.sup.20,
R.sup.21, and R.sup.22 are independently selected from the group
consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino,
dialkylamino, aminoalkyl, and hydroxyalkyl with the provisos that
no more than one of R.sup.20, R.sup.21, and R.sup.22 is hydroxy,
alkoxy, alkylamino, amino, or dialkylamino and that R.sup.20,
R.sup.21, and R.sup.22 must be other than be hydroxy, alkoxy,
alkylamino, amino, and dialkylamino when K.sup.2 is N.sup.+;
Q.sup.b is selected from the group consisting of
N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24), N(R.sup.26)C(O)OR.sup.5,
N(R.sup.26)C(O)SR.sup.5, N(R.sup.26)C(S)OR.sup.5 and
N(R.sup.26)C(S)SR.sup.5 with the proviso that no more than one of
R.sup.23, R.sup.24, and R.sup.26 is hydroxy, alkoxy, alkylamino,
amino, or dialkylamino when two of the group consisting of
R.sup.23, R.sup.24, and R.sup.26 are bonded to the same atom;
Q.sup.b is selected from the group consisting of dialkylsulfonium,
trialkylphosphonium, C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.2- 4),
N(R.sup.26)C(O)N(R.sup.23)(R.sup.24),
N(R.sup.26)C(S)N(R.sup.23)(R.sup- .24), C(NR.sup.25)OR.sup.5,
C(O)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.2- 4),
C(S)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24),
C(NR.sup.25)SR.sup.5, C(O)NR.sup.23R.sup.24, and
C(O)NR.sup.23R.sup.24 with the provisos that no more than one of
R.sup.23, R.sup.24, and R.sup.26 is hydroxy, alkoxy, alkylamino,
amino, or dialkylamino when two of the group consisting of
R.sup.23, R.sup.24, and R.sup.26 are bonded to the same atom and
that said Q.sup.b group is bonded directly to a carbon atom;
R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, alkyl, hydroxy,
alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl;
Q.sup.s is selected from the group consisting of a single covalent
bond, (CR.sup.37R.sup.38).sub.b--(W.sup.0).sub.az wherein az is an
integer selected from 0 through 1, b is an integer selected from 1
through 2, and W.sup.0 is selected from the group consisting of O,
S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.14),
(R.sup.14)NC(O), C(S)N(R.sup.14), (R.sup.14)NC(S),
OC(O)N(R.sup.14), SC(S)N(R.sup.14), SC(O)N(R.sup.14),
OC(S)N(R.sup.14), N(R.sup.15)C(O)N(R.sup.14),
(R.sup.14)NC(O)N(R.sup.15), N(R.sup.15)C(S)N(R.sup.14),
(R.sup.14)NC(S)N(R.sup.15), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, N(R.sup.14),
ON(R.sup.14), (CH(R.sup.14)).sub.c--W.sup.1--(CH(R.sup.15)).sub.d
wherein c and d are integers independently selected from 1 through
2, and W.sup.1 is selected from the group consisting of O, S, C(O),
C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.14), (R.sup.14)NC(O),
C(S)N(R.sup.14), (R.sup.14)NC(S), OC(O)N(R.sup.14),
(R.sup.14)NC(O)O, SC(S)N(R.sup.14), (R.sup.14)NC(S)S,
SC(O)N(R.sup.14), (R.sup.14)NC(O)S, OC(S)N(R.sup.14),
(R.sup.14)NC(S)O, N(R.sup.15)C(O)N(R.sup.14),
(R.sup.14)NC(O)N(R.sup.15), N(R.sup.15)C(S)N(R.sup.14),
(R.sup.14)NC(S)N(R.sup.15), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, N(R.sup.14),
ON(R.sup.14), and
(CH(R.sup.14)).sub.e--W.sup.2--(CH(R.sup.15)).sub.h wherein e and h
are integers independently selected from 0 through 2 and W.sup.2 is
selected from the group consisting of CR.sup.4a.dbd.CR.sup.4b,
ethynylidene (C.ident.C; 1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b
with the provisos that R.sup.14 and R.sup.15 are selected from
other than halo and cyano when directly bonded to N and that
(CR.sup.37R.sup.38).sub.b, (CH(R.sup.14)).sub.c, and
(CH(R.sup.14)).sub.e are bonded to E.sup.0; Y.sup.0 is
Q.sup.b-Q.sup.ss wherein Q.sup.ss is selected from the group
consisting of (CR.sup.37R.sup.38).sub.f wherein f is an integer
selected from 1 through 4,
(CH(R.sup.14)).sub.c--W.sup.1--(CH(R.sup.15)).sub.d wherein c and d
are integers independently selected from 1 through 2, and W.sup.1
is selected from the group consisting of W.sup.1 is selected from
the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,
C(S)S, C(O)N(R.sup.14), (R.sup.14)NC(O), C(S)N(R.sup.14),
(R.sup.14)NC(S), OC(O)N(R.sup.14), (R.sup.14)NC(O)O,
SC(S)N(R.sup.14), (R.sup.14)NC(S)S,
SC(O)N(R.sup.14),(R.sup.14)NC(O)S, OC(S)N(R.sup.14),
(R.sup.14)NC(S)O, N(R.sup.15)C(O)N(R.sup.14),
(R.sup.14)NC(O)N(R.sup.15), N(R.sup.15)C(S)N(R.sup.14),
(R.sup.14)NC(S)N(R.sup.15), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, N(R.sup.14),
ON(R.sup.14), and
(CH(R.sup.14)).sub.e--W.sup.2--(CH(R.sup.15)).sub.h wherein e and h
are integers independently selected from 0 through 2 and W.sup.2 is
selected from the group consisting of CR.sup.4a.dbd.CR.sup.4b,
ethynylidene (C.ident.C; 1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b
with the provisos that R.sup.14 and R.sup.15 are selected from
other than halo when directly bonded to N and that
(CR.sup.37R.sup.38).sub.f, (CH(R.sup.15)).sub.c, and
(CH(R.sup.15)).sub.e are bonded to E.sup.0; Y.sup.0 is
Q.sup.b-Q.sup.sss wherein Q.sup.sss is (CH(R.sup.38)).sub.r--W-
.sup.3, r is an integer selected from 1 through 2, and W.sup.3 is
selected from the group consisting of 1,1-cyclopropyl,
1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl, 1,2-cyclohexyl,
1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl,
2,3-morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl, 2,6-morpholinyl,
3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl,
1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl,
1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl, 2,3-piperidinyl,
2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl,
3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyrrolidinyl,
1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl,
2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-pyranyl, 2H-2,4-pyranyl,
2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-2,4-pyranyl, 4H-2,5-pyranyl,
2H-pyran-2-one-3,4-yl, 2H-pyran-2-one4,5-yl, 4H-pyran-4one-2,3-yl,
2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,
2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl,
2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl,
2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl,
3,4-tetrahydropyranyl, and 3,5-tetrahydropyranyl with the proviso
that (CH(R.sup.38)).sub.r is bonded to E.sup.0 and Q.sub.b is
bonded to lowest numbered substituent position of each W.sup.3;
Y.sup.0 is Q.sup.b-Q.sup.sssr wherein Q.sup.sssr is
(CH(R.sup.38)).sub.r--W.sup.4, r is an integer selected from 1
through 2, and W.sup.4 is selected from the group consisting of
1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl,
1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,
2,5-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl,
1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl,
2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,
1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl,
2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl,
1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl,
4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl,
2H-pyran-2-one-4,5-yl, 4H-pyranone-2,3-yl, 2,3-tetrahydrofuranyl,
2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl,
3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,
2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,
2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and
3,5-tetrahydropyranyl with the provisos that (CH(R.sup.38)).sub.r
is bonded to E.sup.0 and Q.sup.b is bonded to highest number
substituent position of each W.sup.4; Y.sup.0 is Q.sup.b-Q.sup.ssss
wherein Q.sup.ssss is (CH(R.sup.38)).sub.r--W.sup.5, r is an
integer selected from 1 through 2, and W.sup.5 is selected from the
group consisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1
,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl,
3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl,
2,4-benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl,
2,7-benzofuranyl, 3,4-benzofuranyl, 3,5-benzofuranyl,
3,6-benzofuranyl, 3,7-benzofuranyl, 2,4-benzothiophenyl,
2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7-benzothiophenyl,
3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6-benzothiophenyl,
3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl,
2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl,
1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl,
2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl, 1,3-isoindolyl,
3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl,
2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl,
2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl,
3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl,
1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl,
2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl,
2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl,
2,8-quinolinyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl,
3,7-quinolinyl, 3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl,
4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl,
1,5-isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl,
1,8-isoquinolinyl, 3,4-isoquinolinyl, 3,5-isoquinolinyl,
3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8-isoquinolinyl,
4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl,
4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl,
3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl,
4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso that Q.sup.b is
bonded to lowest number substituent position of each W.sup.5 and
that (CH(R.sup.38)).sub.r is bonded to E.sup.0; Y.sup.0 is
Q.sup.b-Q.sup.ssssr wherein Q.sup.ssssr is
(CH(R.sup.38)).sub.r--W.sup.6, r is an integer selected from 1
through 2, and W.sup.6 is selected from the group consisting of
1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl,
2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl,
3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl,
2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,
3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,
2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,
2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,
3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,
2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,
3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,
2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,
1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,
3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,
2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,
3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,
1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl,
1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,
2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,
2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,
3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,
4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,
1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,
1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,
3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,
3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,
4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,
3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,
4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl
with the proviso that Q.sup.b is bonded to highest number
substituent position of each W.sup.6 and that (CH(R.sup.38)).sub.r
is bonded to E.sup.0.
4. The compound as recited in claim 3 or a pharmaceutically
acceptable salt thereof, wherein; 89wherein D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 are independently selected from the
group consisting of C, N, O, S and a covalent bond with the
provisos that no more than one is a covalent bond, no more than one
of D.sup.1, D.sup.2, J.sup.1, J.sup.1 and K.sup.1 is O, no more
than one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 is S,
one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 must be a
covalent bond when two of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and
K.sup.1 are O and S, and no more than four of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 are N; R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36 are independently selected to be Q.sup.b;
R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.32,
R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are independently
selected from the group consisting of hydrido, amidino, guanidino,
dialkylsulfonium, carboxy, haloalkylthio, alkanoyloxy, alkoxy,
alkoxyalkyl, haloalkoxylalkyl, hydroxy, amino, alkoxyamino, thio,
nitro, lower alkylamino, alkylthio, alkylthioalkyl, alkylsulfinyl,
alkylsulfinylalkyl, alkylsulfonyl, alkylsulfonylalkyl,
haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,
alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl
amidosulfonyl, monoarylamidosulfonyl, alkanoyl, alkenoyl,
haloalkanoyl, alkyl, alkenyl, alkenyloxy, alkenyloxyalky, halo,
haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl,
aminoalkyl, haloalkoxyalkyl, carboxyalkyl, carboalkoxy,
alkoxycarboxamido, alkylamidocarbonylamido, carboalkoxyalkyl,
carboalkoxyalkenyl, carboxamido, carboxamidoalkyl, and cyano; B is
selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl,
C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl wherein each
member of group B may be optionally substituted at any carbon up to
and including 6 atoms from the point of attachment of B to A with
one or more of the group consisting of R.sub.32, R.sub.33,
R.sub.34, R.sub.35, and R.sub.36; B is selected from the group
consisting of C3-C1O cycloalkyl, C5-C1O cycloalkenyl, C4-C9
saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl,
wherein each ring carbon may be optionally substituted with
R.sub.33, a ring carbon other than the ring carbon at the point of
attachment of B to A may be optionally substituted with oxo
provided that no more than one ring carbon is substituted by oxo at
the same time, ring carbon and nitrogen atoms adjacent to the
carbon atom at the point of attachment may be optionally
substituted with R.sub.9 or R.sub.13, a ring carbon or nitrogen
atom adjacent to the R.sub.9 position and two atoms from the point
of attachment may be substituted with R.sub.10, a ring carbon or
nitrogen atom adjacent to the R.sub.13 position and two atoms from
the point of attachment may be substituted with R.sub.12, a ring
carbon or nitrogen atom three atoms from the point of attachment
and adjacent to the R.sub.10 position may be substituted with
R.sub.11, a ring carbon or nitrogen atom three atoms from the point
of attachment and adjacent to the R.sub.12 position may be
substituted with R.sub.33, and a ring carbon or nitrogen atom four
atoms from the point of attachment and adjacent to the R.sub.11 and
R.sub.33 positions may be substituted with R.sub.34; A is selected
from the group consisting of single covalent bond,
(W.sup.7).sub.rr--(CH(R.sup.15)).sub.- pa and
(CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr wherein rr is an integer
selected from 0 through 1, pa is an integer selected from 0 through
6, and W.sup.7 is selected from the group consisting of O, S, C(O),
C(S), C(O)S, C(S)O, C(O)N(R.sup.7), C(S)N(R.sup.7), (R.sup.7)NC(O),
(R.sup.7)NC(S), S(O), S(O).sub.2, S(O).sub.2N(R.sup.7),
(R.sup.7)NS(O).sub.2, C(NR.sup.7)N(R.sup.7), (R.sup.7)NC(NR.sup.7),
and N(R.sup.7) with the proviso that no more than one of the group
consisting of rr and pa is 0 at the same time; R.sup.7 and R.sup.8
are independently selected from the group consisting of hydrido,
hydroxy, alkyl, and alkoxyalkyl; R.sup.15 is selected from the
group consisting of hydrido, hydroxy, halo, alkyl, and haloalkyl;
.PSI. is NH; X.sup.0 is hydrido; R.sup.2 is selected from the group
consisting of Z.sup.0-Q, hydrido, alkyl, alkenyl, and halo; Z.sup.0
is a covalent single bond; Q is formula (II): 90wherein D.sup.1,
D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are independently selected
from the group consisting of C, N, O, S and a covalent bond with
the provisos that no more than one is a covalent bond, no more than
one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 is O, no more
than one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 is S,
one of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 must be a
covalent bond when two of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and
K.sup.1 are O and S, and no more than four of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 are N, with the proviso that R.sup.9,
R.sup.10, R.sup.11, R.sup.12, and R.sup.13 are each independently
selected to maintain the tetravalent nature of carbon, trivalent
nature of nitrogen, the divalent nature of sulfur, and the divalent
nature of oxygen; K is CR.sup.4aR.sup.4b; R.sup.4a and R.sup.4b are
independently selected from the group consisting of halo, hydrido,
hydroxy, alkyl, and haloalkyl; E.sup.0 is E.sup.1, when K is
CR.sup.4aR.sup.4b, wherein E.sup.1 is selected from the group
consisting of a covalent single bond, (O)N(H), (H)NC(O), C(S)N(H),
(H)NC(S), S(O).sub.2N(H), N(H)S(O).sub.2, S(O).sub.2N(H)C(O), and
C(O)N(H)S(O).sub.2; K is (CH(R.sup.14)).sub.j-T wherein j is
selected from an integer from 0 through 1 and T is selected from
the group consisting of single covalent bond and N(R.sup.7) with
the proviso that (CH(R.sup.14)).sub.j is bonded to the quinone
ring; R.sup.14 is selected from the group consisting of hydrido,
halo, alkyl, and haloalkyl; E.sup.0 is E.sup.2, when K is
(CH.sup.14).sub.j-T, wherein E.sup.2 is selected from the group
consisting of C(O)N(H), (H)NC(O), C(S)N(H), (H)NC(S),
S(O).sub.2N(H), N(H)S(O).sub.2, S(O).sub.2N(H)C(O), and
C(O)N(H)S(O).sub.2; Y.sup.0 is formula (IV): 91wherein D.sup.5,
D.sup.6, J.sup.5, and J.sup.6 are independently selected from the
group consisting of C, N, O, S and a covalent bond with the
provisos that no more than one is a covalent bond, K.sup.2 is
independently selected from the group consisting of C and N.sup.+,
no more than one of D.sup.5, D.sup.6, J.sup.5, and J.sup.6 is O, no
more than one of D.sup.5, D.sup.6, J.sup.5, and J.sup.6 is S, one
of D.sup.5, D.sup.6, J.sup.5, and J.sup.6 must be a covalent bond
when two of D.sup.5, D.sup.6, J.sup.5, and J.sup.6 are O and S, no
more than three of D.sup.5, D.sup.6, J.sup.5, and J.sup.6 are N
when K.sup.2 is N.sup.+, and no more than four of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 are N when K.sup.2 is carbon with the provisos
that R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are each
independently selected to maintain the tetravalent nature of
carbon, trivalent nature of nitrogen, the divalent nature of
sulfur, and the divalent nature of oxygen; R.sup.16, R.sup.17,
R.sup.18, and R.sup.19 are independently selected from the group
consisting of hydrido, amidino, guanidino, dialkylsulfonium,
carboxy, haloalkylthio, alkoxy, hydroxy, amino, thio, nitro, lower
alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl,
alkenoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl,
haloalkenyl, haloalkoxy, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl,
carboalkoxy, carboalkoxyalkyl, and cyano; Q.sup.b is selected from
the group consisting of NR.sup.20, R.sup.21,
.sup.+NR.sup.20R.sup.21R.sup.22, oxy, alkyl, alkylaminoalkyl,
aminoalkyl, dialkylsulfoniumalkyl, and acylamino wherein R.sup.20,
R.sup.21, and R.sup.22 are independently selected from the group
consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino,
dialkylamino, aminoalkyl, and hydroxyalkyl with the provisos that
no more than one of R.sup.20, R.sup.21, and R.sup.22 is hydroxy,
alkoxy, alkylamino, amino, or dialkylamino and that R.sup.20,
R.sup.21, and R.sup.22 must be other than be hydroxy, alkoxy,
alkylamino, amino, or dialkylamino when K.sup.2 is N; Q.sup.b is
N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24) with the proviso that no
more than one of R.sup.23, R.sup.24, and R.sup.26 is hydroxy,
alkoxy, alkylamino, amino, or dialkylamino when two of the group
consisting of R.sup.23, R.sup.24, and R.sup.26 are bonded to the
same atom; R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are
independently selected from the group consisting of hydrido, alkyl,
hydroxy, alkoxy, alkylamino, dialkylamino, aminoalkyl, and
hydroxyalkyl; Q.sup.b is selected from the group consisting of
dialkylsulfonium, trialkylphosphonium,
C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.2- 4),
N(R.sup.26)C(O)N(R.sup.23)(R.sup.24),
N(R.sup.26)C(S)N(R.sup.23)(R.sup- .24),
C(O)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
C(S)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)C- (NR.sup.25)N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23- )(R.sup.24),
C(O)NR.sup.23R.sup.24, and C(O)NR.sup.23R.sup.24 with the provisos
that no more than one of R.sup.23, R.sup.24, and R.sup.26 is
hydroxy, alkoxy, alkylamino, amino, or dialkylamino when two of the
group consisting of R.sup.23, R.sup.24, and R.sup.26 are bonded to
the same atom and that said Q.sup.b group is bonded directly to a
carbon atom; Q.sup.s is selected from the group consisting of a
single covalent bond and
(CR.sup.37R.sup.38).sub.b--(W.sup.0).sub.az wherein az is an
integer selected from 0 through 1, b is an integer selected from 1
through 2, and W.sup.0 is selected from the group consisting of O,
S, C(O), S(O).sub.2, N(R.sup.14), and ON(R.sup.14) with the proviso
that R.sup.14 is selected from other than halo when directly bonded
to N and that (CR.sup.37R.sup.38).sub.b is bonded to E.sub.0;
R.sup.37 and R.sup.38 are independently selected from the group
consisting of hydrido, halo, alkyl, and haloalkyl; Y.sup.0 is
Q.sup.b-Q.sup.ssss wherein Q.sup.ssss is
(CH(R.sup.38)).sub.r--W.sup.5, r is an integer selected from 1
through 2, and W.sup.5 is selected from the group consisting of
1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl,
2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl,
3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl,
2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,
3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,
2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,
2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,
3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,
2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,
3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,
2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,
1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,
3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,
2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,
3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,
1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl,
1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,
2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,
2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,
3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,
4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,
1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,
1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,
3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,
3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,
4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,
3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,
4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl
with the proviso that, Q.sup.b is bonded to lowest number
substituent position of each W.sup.5 and that (CH(R.sup.38)).sub.r
is bonded to E.sup.0; Y.sup.0 is Q.sup.b-Q.sup.ssssr wherein
Q.sup.ssssr is (CH(R.sup.38)).sub.r--W.sup.6, r is an integer
selected from 1 through 2, and W.sup.6 is selected from the group
consisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl,
2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl,
3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl,
2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl,
3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl,
3,7-benzofuranyl, 2,4-benzothiophenyl, 2,5-benzothiophenyl,
2,6-benzothiophenyl, 2,7-benzothiophenyl, 3,4-benzothiophenyl,
3,5-benzothiophenyl, 3,6-benzothiophenyl, 3,7-benzothiophenyl,
2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl,
3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl,
1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl,
2,6-isoindolyl, 2,7-isoindolyl, 1,3-isoindolyl, 3,4-indazolyl,
3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl,
2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl,
3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl,
3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl,
1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl,
2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl,
2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl,
3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl,
3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl,
4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl,
1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl,
3,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl,
3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl,
4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8-isoquinolinyl,
3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl,
3,8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and
4,8-cinnolinyl with the proviso that Q.sup.b is bonded to highest
number substituent position of each W.sup.6 and that
(CH(R.sup.38)).sub.r is bonded to E.sup.0.
5. The compound as recited in claim 4 having the Formula I-S: 92or
a pharmaceutically acceptable salt thereof, wherein; B is selected
from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl,
3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl,
3-pyrazolyl, 4-pyrazolyl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl,
1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4oxadiazol-3-yl,
1,3,4-oxadiazol-5-yl, 3-isothiazolyl, 5-isothiazolyl, 2-oxazolyl,
2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl,
4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl,
5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 1,3,5-triazin-2-yl,
1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl, and
1,2,3-triazin-4-yl, wherein a carbon adjacent to the carbon at the
point of attachment may be substituted by R.sup.32, the other
carbon adjacent to the carbon at the point of attachment may be
substituted by R.sup.36, a carbon adjacent to R.sup.32 and two
atoms from the carbon at the point of attachment may be substituted
by R.sup.33, a carbon adjacent to R.sup.36 and two atoms from the
carbon at the point of attachment may be substituted by R.sup.35,
and any carbon adjacent to both R.sup.33 and R.sup.35 may be
substituted by R.sup.34; R.sup.32, R.sup.33, R.sup.34, R.sup.35,
and R.sup.36 are independently selected from the group consisting
of hydrido, amidino, guanidino, dimethylsulfonium, carboxy,
methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino,
ethoxyamino, thio, nitro, aminomethyl, 1-aminoethyl, 2-aminoethyl,
N-N-methylamino, dimethylamino, N-ethylamino, methylthio,
ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl,
ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,
N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl,
propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,
2,2,2-trifluoro-1-trifluoromethyl-1-hydro- xyethyl, carboxymethyl,
methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and
Q.sup.b; B is selected from the group consisting of 1-propenyl,
propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl,
sec-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl,
3-pentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl,
1-methyl-2-butenyl, 1-methyl-3-butenyl, 1-methyl-2-butynyl,
3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl,
2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl,
3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl,
3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl,
2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl,
1-methylpentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl,
3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl,
1-ethyl-2-butynyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl,
5-heptenyl, 6-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl,
5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl,
1-methyl-4hexenyl, 1-methyl-5-hexenyl, 1-methyl-2-hexynyl,
1-methyl-3-hexynyl, 1-methylhexynyl, 3-heptyl, 1-ethyl-2-pentenyl,
1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl, 1-butyl-2-propenyl,
1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 1-octyl, 2-octenyl,
3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 2-octynyl,
3-octynyl, 4-octynyl, 5-octynyl, 6-octynyl, 2-octyl,
1-methyl-2-heptenyl, 1-methyl-3-heptenyl, 1-methylheptenyl,
1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-2-heptynyl,
1-methyl-3-heptynyl, 1-methylheptenyl, 1-methyl-5-heptenyl,
1-methylheptenyl, 1-methyl-2-heptenyl, 1-methyl-3-heptynyl,
1-methyl-4-heptynyl, 1-methyl-5-heptynyl, 3-octyl,
1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethyl-4-hexenyl,
1-ethyl-2-hexynyl, 1-ethyl-3-hexynyl, 1-ethyl-4-hexynyl,
1-ethyl-5-hexenyl, 1-pentyl-2-propenyl, 4-octyl,
1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl,
1-butyl-2-butenyl, 1-propyl-2-pentynyl, 1-propyl-3-pentynyl,
1-butyl-2-butynyl, 1-butyl-3-butenyl, 2,2-difluoropropyl,
4-trifluoromethyl-5,5,5-trifluorop- entyl, 4-trifluoromethylpentyl,
5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein each
member of group B may be optionally substituted at any carbon up to
and including 5 atoms from the point of attachment of B to A with
one or more of the group consisting of R.sub.32, R.sub.33,
R.sub.34, R.sub.35, and R.sub.36; B is selected-from the group
consisting of cyclopropyl, cyclobutyl, oxetan-2-yl, oxetan-3-yl,
azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, thiaetan-2-yl,
thiaetan-3-yl, cyclopentyl, cyclopent-2-enyl, cyclopent-3-enyl,
cyclohexyl, 4-methylcyclohexyl, 4-chloro-3-ethylphenoxycyclohexyl,
3-trifluoromethoxyphenoxycyclohexyl, 3-trifluoromethylcyclohexyl,
4-trifluoromethylcyclohexyl, 3,5-bis-trifluoromethylcyclohexyl,
adamantyl, 3-trifluoromethyladamantyl, norbornyl,
3-trifluoromethylnorboy- l, norbornenyl,
7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl,
cyclohex-2-enyl, cyclohex-3-enyl, cycloheptyl, cyclohept-2-enyl,
cyclohept-3-enyl, cyclooctyl, cyclooct-2-enyl, cyclooct-3-enyl,
cyclooctenyl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl,
1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl,
3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl,
3-pyrrolidinyl, 2-dioxanyl, 2H-2-pyranyl, 2H-3-pyranyl,
2H-4-pyranyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-4-pyranyl,
2H-pyran-2-one-3-yl, 2H-pyran-2-one-4-yl, 2H-pyran-2-one-5-yl,
4H-pyran-4one-2-yl, 4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl,
3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl,
4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl,
wherein each ring carbon may be optionally substituted with
R.sub.33, a ring carbon and nitrogen atoms adjacent to the carbon
atom at the point of attachment may be optionally substituted with
R.sub.9 or R.sub.13, a ring carbon or nitrogen atom adjacent to the
R.sub.9 position and two atoms from the point of attachment may be
substituted with R.sub.10, and a ring carbon or nitrogen atom
adjacent to the R.sub.13 position and two atoms from the point of
attachment may be substituted with R.sub.12; R.sup.9, R.sup.10,
R.sup.11, R.sup.12, and R.sup.13 are independently selected from
the group consisting of amidino, guanidino, dimethylsulfonium,
methylethylsulfonium, carboxy, methoxy, ethoxy, isopropoxy,
propoxy, butoxy, hydroxy, amino, methoxyamino, ethoxyamino,
aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N-dimethylamino,
N-methylamino, N-ethylamino, methylsulfinyl, ethylsulfinyl,
methylsulfonyl, ethylsulfonyl, amidosulfonyl,
N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl,
propanoyl, butanoyl, trifluoroacetyl, pentafluoropropanoyl,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
2,2,2-trifluoro-1-hydroxyethyl,
2,2,2-trifluoro-1-trifluoromethyl-1-hydro- xyethyl, carboxymethyl,
2-carboxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano; A is
selected from the group consisting of single covalent bond, O,
C(O), CH.sub.2, CH.sub.3CH, CF.sub.3CH, CH.sub.3CC(O),
CF.sub.3CC(O), C(O)CCH.sub.3, C(O)CCF.sub.3, CH.sub.2C(O),
(O)CCH.sub.2, CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2,
CH.sub.3CCH.sub.2, CF.sub.3CCH.sub.2, CH.sub.3CC(O)CH.sub.2,
CF.sub.3CC(O)CH.sub.2, CH.sub.2C(O)CCH.sub.3,
CH.sub.2C(O)CCF.sub.3, CH.sub.2CH.sub.2C(O), and
CH.sub.2(O)CCH.sub.2; R.sup.2 is selected from the group consisting
of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl,
3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl,
1,2,4-triazol-3-yl, 1,2,4triazol-5-yl, 1,2,4-oxadiazol-3-yl,
1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl,
3-isothiazolyl, 5-isothiazolyl, 2-oxazolyl, 2-thiazolyl,
3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,
2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl,
3-pyridazinyl, 4-pyridazinyl, 1,3,5-triazin-2-yl,
1,2,4triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl, and
1,2,3-triazinyl, wherein a carbon adjacent to the carbon at the
point of attachment may be substituted by R.sup.9, the other carbon
adjacent to the carbon at the point of attachment may be
substituted by R.sup.13, a carbon adjacent to R.sup.9 and two atoms
from the carbon at the point of attachment may be substituted by
R.sup.10, a carbon adjacent to R.sup.13 and two atoms from the
carbon at the point of attachment may be substituted by R.sup.12,
and any carbon adjacent to both R.sup.10 and R.sup.12 may be
substituted by R.sup.11; K is CR.sup.4aR.sup.4b wherein R.sup.4a
and R.sup.4b are independently selected from the group consisting
of chloro, fluoro, and hydrido; E.sup.0 is E.sup.1, when K is
CR.sup.4aR.sup.4b, wherein E.sup.1 is selected from the group
consisting of a covalent single bond, C(O)N(H), (H)NC(O),
S(O).sub.2N(H), N(H)S(O).sub.2, S(O).sub.2N(H)C(O), and
C(O)N(H)S(O).sub.2; K is selected from the group consisting of N(H)
and CH.sub.2N(H); E.sup.0 is E.sup.2, when K is N(H) and
CH.sub.2N(H), wherein E.sup.2 is selected from the group consisting
of C(O)N(H), (H)NC(O), S(O).sub.2N(H), N(H)S(O).sub.2,
S(O).sub.2N(H)C(O), and C(O)N(H)S(O).sub.2; Y.sup.0 is selected
from the group of formulas consisting of: 9394R.sup.16, R.sup.17,
R.sup.18, and R.sup.19 are independently selected from the group
consisting of hydrido, amidino, guanidino, dimethylsulfonium,
carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,
methoxyamino, ethoxyamino, thio, nitro, aminomethyl, 1-aminoethyl,
2-aminoethyl, N-N-methylamino, dimethylamino, N-ethylamino,
methylthio, ethylthio, isopropylthio, trifluoromethylthio,
methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,
N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl,
propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,
2,2,2-trifluoro-1-trifluoromethyl-1-hydro- xyethyl, carboxymethyl,
methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;
Q.sup.b is selected, when bonded to a carbon, from the group
consisting of NR.sup.20R.sup.21, .sup.+NR.sup.20R.sup.21R.sup.22,
dimethylsulfonium, methylethylsulfonium, diethylsulfonium,
trimethylphosphonium, C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.2- 4),
C(O)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24).
N(R.sup.26)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24),
C(O)NR.sup.23R.sup.24, and C(O)NR.sup.23R.sup.24 with the provisos
that no more than one of R.sup.20, R.sup.21, and R.sup.22 is
hydroxy, methoxy, ethoxy, N-methylamino, N,N-dimethylamino,
N,N,N-trimethylamino, or amino and that no more than one of
R.sup.23, R.sup.24, and R.sup.26 is hydroxy, methoxy, ethoxy,
N-methylamino, N,N-dimethylamino, N,N,N-trimethylamino, or amino
when two of the group consisting of R.sup.23, R.sup.24, and
R.sup.26 are bonded to the same atom and that said Q.sup.b group is
bonded directly to a carbon atom; R.sup.20, R.sup.21, R.sup.22,
R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, methyl, ethyl,
propyl, butyl, isopropyl, hydroxy, methoxy, ethoxy, isopropoxy,
propoxy, 2-aminoethyl, 2-(N-methylamino)ethyl,
2-(N,N-dimethylamino)ethyl, 2-(N,N,N-trimethylamino)ethyl,
N-(2-hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino,
N-(2-hydroxyethyl)-N-(2-aminoethyl)amino, N-methylamino,
N-ethylamino, N,N-dimethylamino, N,N-diethylamino, and
N,N,N-trimethylamino; Q.sup.b is selected, when bonded to a
nitrogen, from the group consisting of oxy, methyl, ethyl,
2-aminoethyl, 2-(N-methylamino)ethyl, 2-(N,N-dimethylamino)ethyl,
2-(N,N,N-trimethylamino)ethyl, N-(2-hydroxyethyl)amino,
N,N-bis-(2-hydroxyethyl)amino, amino, hydroxylamino,
N-methoxyamino, N-methylamino, N,N-dimethylamino, and
N,N,N-trimethylamine; Q.sup.s is selected from the group consisting
of a single covalent bond, CH.sub.2, CH.sub.3CH, CF.sub.2,
CF.sub.3CH, CH.sub.2O, CH.sub.3C(H)O, CF.sub.3C(H)O, CH.sub.2S,
CH.sub.3C(H)S, CF.sub.3C(H)S, CH.sub.2C(O), CH.sub.3C(H)C(O),
CF.sub.3C(H)C(O), and CF.sub.2C(O) with the proviso that Q.sup.s is
bonded to E.sup.0 through a carbon atom.
6. The compound as recited in claim 1 or a pharmaceutically
acceptable salt thereof, wherein; B is selected from the group
consisting of aryl and heteroaryl wherein a carbon adjacent to the
carbon at the point of attachment may be substituted by R.sup.32,
the other carbon adjacent to the carbon at the point of attachment
may be substituted by R.sup.36, a carbon adjacent to R.sup.32 and
two atoms from the carbon at the point of attachment may be
substituted by R.sup.33, a carbon adjacent to R.sup.36 and two
atoms from the carbon at the point of attachment may be substituted
by R.sup.35, and any carbon adjacent to both R.sup.33 and R.sup.35
may be substituted by R.sup.34; R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36 are independently selected from the group
consisting of hydrido, amidino, guanidino, dialkylsulfonium,
carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, thio,
nitro, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,
amidosulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl,
haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl,
aminoalkyl, carboxyalkyl, carboalkoxy, carboxamido, cyano, and
Q.sup.b; B is selected from the group consisting of C3-C8 alkyl,
C3-C8 alkenyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl wherein each
member of group B may be optionally substituted at any carbon up to
and including 6 atoms from the point of attachment of B to A with
one or more of the group consisting of R.sub.32, R.sub.33,
R.sub.34, R.sub.35, and R.sub.36; B is selected from the group
consisting of C3-C10 cycloalkyl, C5-C10 cycloalkenyl, C4-C9
saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl,
wherein each ring carbon may be optionally substituted with
R.sub.33, a ring carbon other than the ring carbon at the point of
attachment of B to A may be optionally substituted with oxo
provided that no more than one ring carbon is substituted by oxo at
the same time, ring carbon and nitrogen atoms adjacent to the
carbon atom at the point of attachment may be optionally
substituted with R.sub.9 or R.sub.13, a ring carbon or nitrogen
atom adjacent to the R.sub.9 position and two atoms from the point
of attachment may be substituted with R.sub.10, a ring carbon or
nitrogen atom adjacent to the R.sub.13 position and two atoms from
the point of attachment may be substituted with R.sub.12, a ring
carbon or nitrogen atom three atoms from the point of attachment
and adjacent to the R.sub.10 position may be substituted with
R.sub.11, a ring carbon or nitrogen atom three atoms from the point
of attachment and adjacent to the R.sub.12 position may be
substituted with R.sub.33, and a ring carbon or nitrogen atom four
atoms from the point of attachment and adjacent to the R.sub.11 and
R.sub.33 positions may be substituted with R.sub.34; R.sup.9,
R.sup.10, R.sup.11, R.sup.12, and R.sup.13 are independently
selected from the group consisting of hydrido, amidino, guanidino,
dialkylsulfonium, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
alkoxyamino, thio, nitro, lower alkylamino, alkylthio,
alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkanoyl,
haloalkanoyl, alkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,
hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl,
carboalkoxy, carboxamido, and cyano; A is selected from the group
consisting of single covalent bond,
(W.sup.7).sub.rr--(CH(R.sup.15)).sub.pa and
(CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr wherein rr is an integer
selected from 0 through 1, pa is an integer selected from 0 through
6, and W.sup.7 is selected from the group consisting of O, S, and
C(O) with the proviso that no more than one of the group consisting
of rr and pa is the integer 0 at the same time; R.sup.15 is
selected from the group consisting of hydrido, hydroxy, halo,
alkyl, and haloalkyl; .PSI. is NH; X.sup.0 is hydrido; R.sup.2 is
Q, wherein Q is selected from the group consisting of aryl and
heteroaryl wherein a carbon adjacent to the carbon at the point of
attachment may be substituted by R.sup.9,the other carbon adjacent
to the carbon at the point of attachment may be substituted by
R.sup.13, a carbon adjacent to R.sup.9 and two atoms from the
carbon at the point of attachment may be substituted by R.sup.10, a
carbon adjacent to R.sup.13 and two atoms from the carbon at the
point of attachment may be substituted by R.sup.12, and any carbon
adjacent to both R.sup.10 and R.sup.12 may be substituted by
R.sup.11; K is CR.sup.4aR.sup.4b wherein R.sup.4a and R.sup.4b are
independently selected from the group consisting of halo and
hydrido; E.sup.0 is E.sup.1, when K is CR.sup.4aR.sup.4b, wherein
E.sup.1 is selected from the group consisting of a covalent single
bond, C(O)N(H), (H)NC(O), S(O).sub.2N(H), N(H)S(O).sub.2,
S(O).sub.2N(H)C(O), and C(O)N(H)S(O).sub.2; K is
(CH(R.sup.14)).sub.j-T wherein j is selected from an integer from 0
through 1 and T is selected from the group consisting of single
covalent bond and N(R.sup.7) with the proviso that
(CH(R.sup.14)).sub.j is bonded to the quinone ring; R.sup.7 is
selected from the group consisting of hydrido, hydroxy, alkyl, and
alkoxyalkyl; R.sup.14 is selected from the group consisting of
hydrido and halo; E.sup.0 is E.sup.2, when K is
(CH(R.sup.14)).sub.j-T, wherein E.sup.2 is selected from the group
consisting of C(O)N(H), (H)NC(O), S(O).sub.2N(H), N(H)S(O).sub.2,
S(O).sub.2N(H)C(O), and C(O)N(H)S(O).sub.2; Y.sup.0 is formula
(IV): 95wherein D.sup.5, D.sup.6, J.sup.5, and J.sup.6 are
independently selected from the group consisting of C, N, O, S and
a covalent bond with the provisos that no more than one is a
covalent bond, K.sup.2 is independently selected from the group
consisting of C and N.sup.+, no more than one of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 is O, no more than one of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 is S, one of D.sup.5, D.sup.6, J.sup.5, and
J.sup.6 must be a covalent bond when two of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 are O and S, no more than three of D.sup.5,
D.sup.6, J.sup.5, and J.sup.6 are N when K.sup.2 is N.sup.', and no
more than four of D.sup.5, D.sup.6, J.sup.5, and J.sup.6 are N when
K.sup.2 is carbon with the provisos that R.sup.16, R.sup.17,
R.sup.18, and R.sup.19 are each independently selected to maintain
the tetravalent nature of carbon, trivalent nature of nitrogen, the
divalent nature of sulfur, and the divalent nature of oxygen;
R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, amidino, guanidino,
dialkylsulfonium, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
thio, nitro, lower alkylamino, alkylthio, alkylsulfinyl,
alkylsulfonyl, alkanoyl, alkenoyl, haloalkanoyl, alkyl, alkenyl,
halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, aminoalkyl,
haloalkoxyalkyl, carboalkoxy, carboalkoxyalkyl, and cyano; Q.sup.b
is selected from the group consisting of NR.sup.20R.sup.21,
.sup.+NR.sup.20R.sup.21R.sup.22, oxy, alkyl, alkylaminoalkyl,
aminoalkyl, dialkylsulfoniumalkyl, and acylamino wherein R.sup.20,
R.sup.21, and R.sup.22 are independently selected from the group
consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino,
dialkylamino, aminoalkyl, and hydroxyalkyl with the provisos that
no more than one of R.sup.20, R.sup.21, and R.sup.22 is hydroxy,
alkoxy, alkylamino, amino, or dialkylamino and that R.sup.20,
R.sup.21, and R.sup.22 must be other than be hydroxy, alkoxy,
alkylamino, amino, or dialkylamino when K.sup.2 is N.sup.+; Q.sup.b
is selected from the group consisting of dialkylsulfonium,
trialkylphosphonium, C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
C(O)N(R.sup.26)C(NR.sup.25)- N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup- .24),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24),
C(O)NR.sup.23R.sup.24, and C(O)NR.sup.23R.sup.24 with the provisos
that no more than one of R.sup.23, R.sup.24, and R.sup.26 is
hydroxy, alkoxy, alkylamino, amino, or dialkylamino when two of the
group consisting of R.sup.23 R.sup.24, and R.sup.26 are bonded to
the same atom and that said Q.sup.b group is bonded directly to a
carbon atom; R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are
independently selected from the group consisting of hydrido, alkyl,
hydroxy, alkoxy, alkylamino, dialkylamino, aminoalkyl, and
hydroxyalkyl; Q.sup.s is selected from the group consisting of a
single covalent bond and (CR.sup.37R.sup.38).sub.b--(W.su-
p.0).sub.az wherein az is an integer selected from 0 through 1, b
is the integer 1, and W.sup.0 is selected from the group consisting
of O, S, and C(O) with the proviso that (CR.sup.37R.sup.38).sub.b
is bonded to E.sup.0; R.sup.37 and R.sup.38 are independently
selected from the group consisting of hydrido, halo, alkyl, and
haloalkyl.
7. The compound as recited in claim 6 having the Formula I-MPS:
96or a pharmaceutically acceptable salt thereof, wherein; B is
selected from the group consisting of phenyl, 2-thienyl, 3-thienyl,
2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,
4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl,
5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl,
2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,
4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a carbon adjacent to
the carbon at the point of attachment may be substituted by
R.sup.32, the other carbon adjacent to the carbon at the point of
attachment may be substituted by R.sup.36, a carbon adjacent to
R.sup.32 and two atoms from the carbon at the point of attachment
may be substituted by R.sup.33, a carbon adjacent to R.sup.36 and
two atoms from the carbon at the point of attachment may be
substituted by R.sup.35, and any carbon adjacent to both R.sup.33
and R.sup.35 may be substituted by R.sup.34; R.sup.32, R.sup.33,
R.sup.34, R.sup.35, and R.sup.36 are independently selected from
the group consisting of hydrido, amidino, guanidino,
dimethylsulfonium, carboxy, methoxy, ethoxy, isopropoxy, propoxy,
hydroxy, amino, methoxyamino, ethoxyamino, thio, nitro,
aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N-methylamino,
dimethylamino, N-ethylamino, methylthio, ethylthio,
trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,
ethylsulfonyl, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,
acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
2,2,2-trifluoro-1-hydroxyethyl,
2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl,
methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and
Q.sup.b; B is selected from the group consisting of 1-propenyl,
propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, sec-butyl,
isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl,
4-pentenyl, 2-pentyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl,
3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl,
2-methyl-3-butenyl, 3-methylbutyl, 3-methyl-2-butenyl,
3-methyl-3-butenyl, 2,2-difluoropropyl,
2-trifluoromethyl-3,3,3-trifluoro- propyl,
1,1,1,2,2,2-hexafluoropropyl, 3,3,3-trifluoroprop-1-yl, and
3,3,3-trifluoroprop-2-yl, wherein each member of group B may be
optionally substituted at any carbon up to and including 5 atoms
from the point of attachment of B to A with one or more of the
group consisting of R.sub.32, R.sub.33, R.sub.34, R.sub.35, and
R.sub.36; B is selected from the group consisting of cyclopropyl,
cyclobutyl, oxetan-2-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl,
azetidin-3-yl, thiaetan-2-yl, thiaetan-3-yl, wherein each ring
carbon may be optionally substituted with R.sub.33, a ring carbon
and nitrogen atoms adjacent to the carbon atom at the point of
attachment may be optionally substituted with R.sub.9 or R.sub.13,
a ring carbon or nitrogen atom adjacent to the R.sub.9 position and
two atoms from the point of attachment may be substituted with R10,
and a ring carbon or nitrogen atom adjacent to the R.sub.13
position and two atoms from the point of attachment may be
substituted with R.sub.12; R.sup.9, R.sup.10, R.sup.11, R.sup.12,
and R.sup.13 are independently selected from the group consisting
of amidino, guanidino, dimethylsulfonium, carboxy, methoxy, ethoxy,
isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,
aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N-methylamino,
dimethylamino, N-ethylamino, methylsulfinyl, ethylsulfinyl,
methylsulfonyl, ethylsulfonyl, amidosulfonyl,
N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl,
propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,
2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl,
methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano; A is
selected from the group consisting of single covalent bond, O,
C(O), CH.sub.2, CH.sub.3CH, CF.sub.3CH, CH.sub.3CC(O),
CF.sub.3CC(O), CC(O)CCH.sub.3, C(O)CCF.sub.3, CH.sub.2C(O), and
(O)CCH.sub.2; R.sup.2 is selected from the group consisting of
phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl,
3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl,
2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl,
4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl,
5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and
1,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at the
point of attachment may be substituted by R.sup.9,the other carbon
adjacent to the carbon at the point of attachment may be
substituted by R.sup.13, a carbon adjacent to R.sup.9 and two atoms
from the carbon at the point of attachment may be substituted by
R.sup.10, a carbon adjacent to R.sup.13 and two atoms from the
carbon at the point of attachment may be substituted by R.sup.12,
and any carbon adjacent to both R.sup.10 and R.sup.12 may be
substituted by R.sup.11; K is CR.sup.4aR.sup.4b wherein R.sup.4a
and R.sup.4b are independently selected from the group consisting
of chloro, fluoro, and hydrido; E.sup.0 is E.sup.1, when K is
CR.sup.4aR.sup.4b, wherein E.sup.1 is selected from the group
consisting of a covalent single bond, C(O)N(H), (H)NC(O),
S(O).sub.2N(H), N(H)S(O).sub.2, S(O).sub.2N(H)C(O), and
C(O)N(H)S(O).sub.2; K is selected from the group consisting of N(H)
and CH.sub.2N(H); E.sup.0 is E.sup.2, when K is selected from the
group consisting of N(H) and C.sub.2N(H), wherein E.sup.2 is
selected from the group consisting of C(O)N(H), (H)NC(O),
S(O).sub.2N(H), N(H)S(O).sub.2, S(O).sub.2N(H)C(O), and
C(O)N(H)S(O).sub.2; Y.sup.0 is selected from the group of formulas
consisting of: 9798R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are
independently selected from the group consisting of hydrido,
amidino, guanidino, methoxy, ethoxy, isopropoxy, methylthio, ethyl
thio, trifluoromethylthio, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3 -pentafluoropropyl,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl,
methoxycarbonyl, ethoxycarbonyl, and cyano; Q.sup.b is selected,
when bonded to a carbon, from the group consisting of
NR.sup.20R.sup.21, .sup.+NR.sup.20R.sup.21R.sup.22,
dimethylsulfonium, methylethylsulfonium, diethylsulfonium,
trimethylphosphonium, C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
C(O)N(R.sup.26)C(NR.sup.25)- N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup- .24),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24),
C(O)NR.sup.23R.sup.24, and C(O)NR.sup.23R.sup.24 with the provisos
that no more than one of R.sup.20, R.sup.21, and R.sup.22 is
hydroxy, methoxy, ethoxy, N-methylamino, N,N-dimethylamino,
N,N,N-trimethylamino, or amino and that no more than one of
R.sup.23, R.sup.24, and R.sup.26 is hydroxy, methoxy, ethoxy,
N-methylamino, N,N-dimethylamino, N,N,N-trimethylamino, or amino
when two of the group consisting of R.sup.23, R.sup.24, and
R.sup.26 are bonded to the same atom and that said Q.sup.b group is
bonded directly to a carbon atom; R.sup.20, R.sup.21, R.sup.22,
R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, methyl, ethyl,
hydroxy, methoxy, ethoxy, 2-aminoethyl, 2-(N-methylamino)ethyl,
2-(N,N-dimethylamino)ethyl, 2-(N,N,N-trimethylamino)ethyl,
N-(2-hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino,
N-(2-hydroxyethyl)-N-(2-aminoethyl)amino, N-methylamino,
N,N-dimethylamino, and N,N,N-trimethylamino; Q.sup.b is selected,
when bonded to a nitrogen, from the group consisting of oxy,
methyl, ethyl, 2-aminoethyl, 2-(N-methylamino)ethyl,
2-(N,N-dimethylamino)ethyl, 2-(N,N,N-trimethylamino)ethyl,
N-(2-hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino, amino,
hydroxylamino, N-methoxyamino, N-methylamino, N,N-dimethylamino,
and N,N,N-trimethylamino; Q.sup.s is selected from the group
consisting of a single covalent bond, CH.sub.2, CH.sub.3CH,
CF.sub.2, CF.sub.3CH, CH.sub.20, CH.sub.3C(H)O, CF.sub.3C(H)O,
CH.sub.2S, CH.sub.3C(H)S, CF.sub.3C(H)S, CH.sub.2C(O),
CH.sub.3C(H)C(O), CF.sub.3C(H)C(O), and CF.sub.2C(O) with the
proviso that Q.sup.s is bonded to E.sup.0 through a carbon
atom.
8. The compound as recited in claim 7 having the Formula I-EMPS:
99or a pharmaceutically acceptable salt thereof, wherein; B is
selected from the group consisting of phenyl, 2-thienyl, 3-thienyl,
2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,
4imidazolyl, 3-pyrazolyl, 4pyrazolyl, 2-thiazolyl, 3-isoxazolyl,
5-isoxazolyl, 2-pyridyl, 3-pyridyl, and 4-pyridyl, wherein a carbon
adjacent to the carbon at the point of attachment may be
substituted by R.sup.32, the other carbon adjacent to the carbon at
the point of attachment may be substituted by R.sup.36, a carbon
adjacent to R.sup.32 and two atoms from the carbon at the point of
attachment may be substituted by R.sup.33, a carbon adjacent to
R.sup.36 and two atoms from the carbon at the point of attachment
may be substituted by R.sup.35, and any carbon adjacent to both
R.sup.33 and R.sup.35 may be substituted by R.sup.34; R.sup.32,
R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are independently
selected from the group consisting of hydrido, amidino, guanidino,
methoxy, ethoxy, hydroxy, amino, methoxyamino, ethoxyamino,
aminomethyl, 1-aminoethyl, 2-aminoethyl, N--N-methylamino,
dimethylamino, N-ethylamino, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, fluoro, chloro,
bromo, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
2,2,2-trifluoro-1-hydroxyethyl,
2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, methoxycarbonyl,
ethoxycarbonyl, cyano, and Q.sup.b; B is selected from the group
consisting of propyl, isopropyl, butyl, sec-butyl, isobutyl,
1-pentyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 3-methylbutyl,
2,2-difluoropropyl, 2-trifluoromethyl-3,3,3-trifluoropropyl,
1,1,1,2,2,2-hexafluoropropyl, 3,3,3-trifluoroprop-1-yl, and
3,3,3-trifluoroprop-2-yl, wherein each member of group B may be
optionally substituted at any carbon up to and including 5 atoms
from the point of attachment of B to A with one or more of the
group consisting of R.sub.32, R.sub.33, R.sub.34, R.sub.35, and
R.sub.36; B is selected from the group consisting of cyclopropyl,
cyclobutyl, oxetan-2-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl,
azetidin-3-yl, thiaetan-2-yl, thiaetan-3-yl, wherein each ring
carbon may be optionally substituted with R.sub.33, a ring carbon
and nitrogen atoms adjacent to the carbon atom at the point of
attachment may be optionally substituted with R.sub.9 or R.sub.13,
a ring carbon or nitrogen atom adjacent to the R.sub.9 position and
two atoms from the point of attachment may be substituted with
R.sub.10, and a ring carbon or nitrogen atom adjacent to the
R.sub.13 position and two atoms from the point of attachment may be
substituted with R.sub.12; R.sup.9, R.sup.10, R.sup.11, R.sup.12,
and R.sup.13 are independently selected from the group consisting
of amidino, guanidino, carboxy, methoxy, ethoxy, hydroxy, amino,
methoxyamino, ethoxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl,
N--N-methylamino, dimethylamino, N-ethylamino, acetyl, propanoyl,
trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, carboxymethyl, methoxycarbonyl,
ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,
N,N-dimethylamidocarbonyl, and cyano; A is selected from the group
consisting of single covalent bond, O, C(O), CH.sub.2,
CH.sub.2C(O), and (O)CCH.sub.2; R.sup.2 is selected from the group
consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl,
2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4imidazolyl, 3-pyrazolyl,
4pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5isoxazolyl, 2-pyridyl,
3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4pyrimidinyl,
5pyrimidinyl, 3-pyridazinyl, 4pyridazinyl, and 1,3,%triazin-2-yl,
wherein a carbon adjacent to the carbon at the point of attachment
may be substituted by R.sup.9, the other carbon adjacent to the
carbon at the point of attachment may be substituted by R.sup.13, a
carbon adjacent to R.sup.9 and two atoms from the carbon at the
point of attachment may be substituted by R.sup.10, a carbon
adjacent to R.sup.13 and two atoms from the carbon at the point of
attachment may be substituted by R.sup.12, and any carbon adjacent
to both R.sup.10 and R.sup.12 may be substituted by R.sup.11; K is
CR.sup.4aR.sup.4b wherein R.sup.4a and R.sup.4b are independently
selected from the group consisting of chloro, fluoro, and hydrido;
E.sup.0is E.sup.1, when K is CR.sup.4aR.sup.4b, wherein E.sup.1 is
selected from the group consisting of a covalent single bond,
C(O)N(H), (H)NC(O), S(O).sub.2N(H), N(H)S(O).sub.2,
S(O).sub.2N(H)C(O), and C(O)N(H)S(O).sub.2; K is selected from the
group consisting of N(H) and CH.sub.2N(H); E.sup.0 is E.sup.2, when
K is selected from the group consisting of N(H) and CH.sub.2N(H),
wherein E.sup.2 is selected from the group consisting of C(O)N(H),
(H)NC(O), S(O).sub.2N(H), N(H)S(O).sub.2, S(O).sub.2N(H)C(O), and
C(O)N(H)S(O).sub.2; Y.sup.0 is selected from the group of formulas
consisting of: 100101R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are
independently selected from the group consisting of hydrido,
methoxy, ethoxy, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, trifluoromethoxy, fluoro, chloro, bromo,
acetyl, trifluoroacetyl, methoxycarbonyl, ethoxycarbonyl, and
cyano; Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, .sup.+NR.sup.20R.sup.21R.sup.22,
dimethylsulfonium, methylethylsulfonium, diethylsulfonium,
trimethylphosphonium, C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
C(O)N(R.sup.26)C(NR.sup.25)- N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup- .24),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24),
C(O)NR.sup.23R.sup.24, and C(O)NR.sup.23R.sup.24 with the provisos
that no more than one of R.sup.20, R.sup.21, and R.sup.22 is
hydroxy, methoxy, ethoxy, N-methylamino, N,N-dimethylamino, and
N,N,N-trimethylamino, or amino and that no more than one of
R.sup.23, R.sup.24, and R.sup.26 is hydroxy, methoxy, ethoxy,
N-methylamino, N,N-dimethylamino, N,N,N-trimethylamino, or amino
when two of the group consisting of R.sup.23, R.sup.24, and
R.sup.26 are bonded to the same atom; R.sup.20, R.sup.21, R.sup.22,
R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, methyl, ethyl,
hydroxy, methoxy, ethoxy, 2-aminoethyl, 2-(N-methylamino)ethyl,
2-(N,N-dimethylamino)ethyl, 2-(N,N,N-trimethylamino)ethyl,
N-(2-hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino,
N-(2-hydroxyethyl)-N-(2-aminoethyl)amino, N-methylamino,
N,N-dimethylamino, and N,N,N-trimethylamino; Q.sup.s is selected
from the group consisting of a single covalent bond, CH.sub.2,
CH.sub.3CH, CF.sub.2, CF.sub.3CH, CH.sub.2O, CH.sub.3C(H)O,
CF.sub.3C(H)O, CH.sub.2C(O), CH.sub.3C(H)C(O), CF.sub.3C(H)C(O),
and CF.sub.2C(O) with the proviso that Q.sup.s is bonded to E.sup.0
through a carbon atom.
9. A composition for inhibiting thrombotic conditions in blood
comprising a compound of any one of claims 1 through 8 and a
pharmaceutically acceptable carrier.
10. A method for inhibiting thrombotic conditions in blood
comprising adding to blood a therapeutically effective amount of a
composition of claim 9.
11. A method for inhibiting formation of blood platelet aggregates
in blood comprising adding to blood a therapeutically effective
amount of a composition of claim 9.
12. A method for inhibiting thrombus formation in blood comprising
adding to blood a therapeutically effective amount of a composition
of claim 9.
13. A method for treating or preventing venuous thromboembolism and
pulmonary embolism in a mammal comprising administering to the
mammal a therapeutically effective amount of a composition of claim
9.
14. A method for treating or preventing deep vein thrombosis in a
mammal comprising administering to the mammal a therapeutically
effective amount of a composition of claim 9.
15. A method for treating or preventing cardiogenic thromboembolism
in a mammal comprising administering to the mammal a
therapeutically effective amount of a composition of claim 9.
16. A method for treating or preventing thromboembolic stroke in
humans and other mammals comprising administering to the mammal a
therapeutically effective amount of a composition of claim 9.
17. A method for treating or preventing thrombosis associated with
cancer and cancer chemotherapy in humans and other mammals
comprising administering to the mammal a therapeutically effective
amount of a composition of claim 9.
18. A method for treating or preventing unstable angina in humans
and other mammals comprising administering to the mammal a
therapeutically effective amount of a composition of claim 9.
19. A method for inhibiting thrombus formation in blood comprising
adding to blood a therapeutically effective amount of a compound of
any one of claims 1 through 8 with a therapeutically effective
amount of fibrinogen receptor antagonist.
20. The use of a compound of any one of claims 1 through 8, or a
pharmaceutically acceptable salt thereof, in the manufacture of
medicament for inhibiting thrombus formation, treating thrombus
formation, or preventing thrombus formation in a mammal.
21. A compound of the Formula: 102or a pharmaceutically acceptable
salt thereof, wherein; B is phenyl or a heteroaryl of 5 or 6 ring
members, wherein a nitrogen with a removable hydrogen or a carbon
adjacent to the carbon at the point of attachment of said phenyl or
heteroaryl ring to A is optionally substituted by R.sup.32, a
nitrogen with a removable hydrogen or a carbon at the other
position adjacent to the point of attachment is optionally
substituted by R.sup.36, a nitrogen with a removable hydrogen or a
carbon adjacent to R.sup.32 and two atoms from the point of
attachment is optionally substituted by R.sup.33, a nitrogen with a
removable hydrogen or a carbon adjacent to R.sup.36 and two atoms
from the point of attachment is optionally substituted by R.sup.35,
and a nitrogen with a removable hydrogen or a carbon adjacent to
both R.sup.33 and R.sup.35 is optionally substituted by R.sup.34;
R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.32,
R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are independently
selected from the group consisting of hydrido, acetamido,
haloacetamido, amidino, guanidino, alkylenedioxy, haloalkylthio,
alkanoyloxy, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy,
aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy,
heterocyclylalkoxy, alkoxyalkyl, haloalkoxylalkyl, hydroxy, amino,
alkoxyamino, nitro, alkylamino, N-alkyl-N-arylamino, arylamino,
aralkylamino, heteroarylamino, heteroaralkylamino,
heterocyclylamino, heterocyclylalkylamino, alkylthio,
alkylthioalkyl, alkylsulfinyl, arylsulfinyl, aralkylsulfinyl,
cycloalkylsulfinyl, heteroarylsulfinyl, alkylsulfonyl,
arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl,
heteroarylsulfonyl, alkylsulfonylalkyl, aryl, aralkyl, cycloalkyl,
cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido,
aminosulfonyl, alkanoyl, haloalkanoyl, alkyl, alkenyl, halo,
haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl,
aminoalkyl, haloalkoxyalkyl, carboxyalkyl, carboalkoxy, carboxy,
carboxamido, carboxamidoalkyl, and cyano; R.sup.32, R.sup.33,
R.sup.34, R.sup.35, and R.sup.36 are independently optionally
Q.sup.b; B is optionally selected from the group consisting of
hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8
alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of
group B is optionally substituted at any carbon up to and including
6 atoms from the point of attachment of B to A with one or more of
the group consisting of R.sup.32, R.sup.33, R.sup.34, R.sup.35, and
R.sup.36; B is optionally a C3-C12 cycloalkyl or C4C9 saturated
heterocyclyl, wherein each ring carbon is optionally substituted
with R.sup.33, a ring carbon other than the ring carbon at the
point of attachment of B to A is optionally substituted with oxo
provided that no more than one ring carbon is substituted by oxo at
the same time, ring carbons and a nitrogen adjacent to the carbon
atom at the point of attachment are optionally substituted with
R.sup.9 or R.sup.13, a ring carbon or nitrogen atom adjacent to the
R.sup.9 position and two atoms from the point of attachment is
optionally substituted with R.sup.10, a ring carbon or nitrogen
adjacent to the R.sup.13 position and two atoms from the point of
attachment is optionally substituted with R.sup.12, a ring carbon
or nitrogen three atoms from the point of attachment and adjacent
to the R.sup.10 position is optionally substituted with R.sup.11, a
ring carbon or nitrogen three atoms from the point of attachment
and adjacent to the R.sup.12 position is optionally substituted
with R.sup.33, and a ring carbon or nitrogen four atoms from the
point of attachment and adjacent to the R.sup.11 and R.sup.33
positions is optionally substituted with R.sup.34; A is selected
from the group consisting of a bond,
(W.sup.7).sub.rr--(CH(R.sup.15)).sub.pa, and
(CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr wherein rr is 0 or 1, pa is
an integer selected from 0 through 6, and W.sup.7 is selected from
the group consisting of O, S, C(O), (R.sup.7)NC(O), (R.sup.7)NC(S),
and N(R.sup.7) with the proviso that no more than one of the group
consisting of rr and pa is 0 at the same time; R.sup.7 is selected
from the group consisting of hydrido, hydroxy, and alkyl; R.sup.15
is selected from the group consisting of hydrido, hydroxy, halo,
alkyl, and haloalkyl; .PSI. is NH or NOH; X.sup.0 is selected from
the group consisting of hydrido, alkyl, alkenyl, cyano, halo,
haloalkyl, haloalkoxy, haloalkylthio, amino, aminoalkyl,
alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl,
alkoxyamino, thiol, and alkylthio; R.sup.2 is Z.sup.0-Q; Z.sup.0 is
selected from the group consisting of a bond,
(CR.sup.41R.sup.42).sub.q wherein q is an integer selected from 1
through 3, and (CH(R.sup.41)).sub.g--W.sup.0--(CH(R.sup.42)).sub.p
wherein g and p are integers independently selected from 0 through
3 and W.sup.0 is selected from the group consisting of O, S, C(O),
S(O), N(R.sup.41), and ON(R.sup.41); Z.sup.0 is optionally
(CH(R.sup.41)).sub.e--W.sup.22--(CH(R- .sup.42)).sub.h wherein e
and h are independently 0 or 1 and W.sup.22 is selected from the
group consisting of CR.sup.41.dbd.CR.sup.42, 1,2-cyclopropyl,
1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl,
1,3-cyclopentyl, 2,3-morpholinyl, 2,4morpholinyl, 2,6-morpholinyl,
3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl,
2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,
2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl,
1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,
2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, wherein Z.sup.0
is directly bonded to the 1,4-quinone ring and W.sup.22 is
optionally substituted with one or more substituents selected from
the group consisting of R.sup.9, R.sup.10, R.sup.11, R.sup.12, and
R.sup.13; R.sup.41 and R.sup.42 are independently selected from the
group consisting of amidino, hydroxyamino, hydrido, hydroxy, amino,
and alkyl; Q is phenyl or a heteroaryl of 5 or 6 ring members,
wherein a nitrogen with a removable hydrogen or a carbon adjacent
to the carbon at the point of attachment of said phenyl or
heteroaryl ring to Z.sup.0 is optionally substituted by R.sup.9, a
nitrogen with a removable hydrogen or a carbon at the other
position adjacent to the point of attachment is optionally
substituted by R.sup.13, a nitrogen with a removable hydrogen or a
carbon adjacent to R.sup.9 and two atoms from the point of
attachment is optionally substituted by R.sup.10, a nitrogen with a
removable hydrogen or a carbon adjacent to R.sup.13 and two atoms
from the point of attachment is optionally substituted by R.sup.12,
and a nitrogen with a removable hydrogen or a carbon adjacent to
both R.sup.10 and R.sup.12 is optionally substituted by R.sup.11; Q
is optionally hydrido with the proviso that Z.sup.0 is selected
from other than a bond; K is CR.sup.4aR.sup.4b; R.sup.4a and
R.sup.4b are independently selected from the group consisting of
halo, hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl,
and haloalkyl; E.sup.0, with the proviso that K is
CR.sup.4aR.sup.4b, is E.sup.1 wherein E.sup.1 is selected from the
group consisting of a covalent single bond, C(O)N(H), (H)NC(O),
C(S)N(H), (H)NC(S), S(O).sub.2N(H), N(H)S(O).sub.2,
S(O).sub.2N(H)C(O), and C(O)N(H)S(O).sub.2; K is optionally
(CH(R.sup.14)).sub.j-T wherein j is 0 or 1 and T is a bond or
N(R.sup.7) with the proviso that (CH(R.sup.14)).sub.j is bonded to
the phenyl ring; R.sup.14 is selected from the group consisting of
hydrido, halo, alkyl, and haloalkyl; E.sup.0, with the proviso that
K is (CH(R.sup.14)).sub.j-T, is E.sup.2wherein E.sup.2 is selected
from the group consisting of C(O)N(H), (H)NC(O), C(S)N(H),
(H)NC(S), S(O).sub.2N(H), N(H)S(O).sub.2, S(O).sub.2N(H)C(O), and
C(O)N(H)S(O).sub.2; Y.sup.0 is phenyl or a heteroaryl of 5 or 6
ring members, wherein one carbon of said phenyl or said heteroaryl
is substituted by Q.sup.s, a carbon two or three contiguous atoms
from the point of attachment of Q.sup.s to said phenyl or said
heteroaryl to said phenyl or said heteroaryl is substituted by
Q.sup.b, a carbon adjacent to the point of attachment of Q.sup.s is
optionally substituted by R.sup.17, another carbon adjacent to the
point of attachment of Q.sup.s is optionally substituted by
R.sup.18, a carbon adjacent to Q.sup.b is optionally substituted by
R.sup.16, and another carbon adjacent to Q.sup.b is optionally
substituted by R.sup.19; R.sup.16, R.sup.17, R.sup.18, and R.sup.19
are independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
nitro, alkoxyamino, alkylamino, alkylthio, alkylsulfinyl,
alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, alkenyl, halo,
haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl,
carboalkoxy, and cyano; R.sup.16 or R.sup.19 is optionally selected
from the group consisting of NR.sup.20R.sup.21,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24), and
C(NR.sup.25)NR.sup.23R.- sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido; Q.sup.b is
selected from the group consisting of NR.sup.20R.sup.21,
aminoalkyl, hydrido, N(R.sup.26)C(NR.sup.25)N(R.sup.23-
)(R.sup.24), and C(NR.sup.25)NR.sup.23R.sup.24, with the proviso
that no more than one of R.sup.20 and R.sup.21 is selected from the
group consisting of hydroxy, amino, alkylamino, and dialkylamino at
the same time, with the further proviso that no more than one of
R.sup.23 and R.sup.24 is selected from the group consisting of
hydroxy, amino, alkylamino, and dialkylamino at the same time;
R.sup.20, R.sup.21, R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are
independently selected from the group consisting of hydrido, alkyl,
hydroxy, aminoalkyl, amino, dialkylamino, alkylamino, and
hydroxyalkyl; Q.sup.s is selected from the group consisting of a
bond, (CR.sup.37R.sup.38).sub.b wherein b is an integer selected
from 1 through 4, and (CH(R.sup.14)).sub.c--W.sup.1--(CH-
(R.sup.15)).sub.d wherein c and d are integers independently
selected from 1 through 3 and W.sup.1 is selected from the group
consisting of C(O)N(R.sup.14), (R.sup.14)NC(O), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, and N(R.sup.14), with
the proviso that R.sup.14 is selected from other than halo when
directly bonded to N, and with the additional proviso that
(CR.sup.37R.sup.38).sub- .b and (CH(R.sup.14)).sub.c are bonded to
E.sup.0; R.sup.37 and R.sup.38 are independently selected from the
group consisting of hydrido, alkyl, and haloalkyl; R.sup.38 is
optionally aroyl or heteroaroyl, wherein R.sup.38 is optionally
substituted with one or more substituents selected from the group
consisting of R.sup.16, R.sup.17, R.sup.18, and R.sup.19; Y.sup.0
is optionally Y.sup.AT wherein Y.sup.AT is Q.sup.b-Q.sup.s; Y.sup.0
is optionally Q.sup.b-Q.sup.ss wherein Q.sup.ss is
(CH(R.sup.14)).sub.e--W.sup.2--(CH(R.sup.15)).sub.h, wherein e and
h are independently 1 or 2 and W.sup.2 is CR.sup.4a.dbd.CR.sup.4b,
with the proviso that (CH(R.sup.14)).sub.e is bonded to E.sup.0;
Y.sup.0 is optionally Q.sup.b-Q.sup.ssss or Q.sup.b-Q.sup.ssssr
wherein Q.sup.ssss is (CH(R.sup.38)).sub.r--W.sup.5,Q.sup.ssssr is
(CH(R.sup.38)).sub.r--W.s- up.6, r is 1 or 2, W.sup.5 and W.sup.6
are independently selected from the group consisting of
1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl,
2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl,
3,6-indenyl, 3,7-indenyl, 2,4benzofuranyl, 2,5-benzofuranyl,
2,6-benzofuranyl, 2,7-benzofuranyl, 3,4benzofuranyl,
3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,
2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,
2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,
3,6-benzothiophenyl, 3,7-benzothiophenyl,
2,7-imidazo(1,2-a)pyridinyl, 3,4-imidazo(1,2-a)pyrid- inyl,
3,5-imidazo(1,2-a)pyridinyl, 3,6-imidazo(1,2-a)pyridinyl,
3,7-imidazo(1,2-a)pyridinyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl,
2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl,
1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl,
2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl, 1,3-isoindolyl,
3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl,
2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl,
2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl,
3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl,
1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl,
2,-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl,
2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl,
2,8-quinolinyl, 3,4-quinolinyl, 3,5;-quinolinyl, 3,6-quinolinyl,
3,7-quinolinyl, 3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl,
4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl,
1,5-isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl,
1,8-isoquinolinyl, 3,4-isoquinolinyl, 3,5-isoquinolinyl,
3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8-isoquinolinyl,
4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl,
4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl,
3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl,
4,7-cinnolinyl, and 4,8cinnolinyl, and each carbon and hyrido
containing nitrogen member of the ring of the W.sup.5 and of the
ring of the W.sup.6, other than the points of attachment of W.sup.5
and W.sup.6 is optionally substituted with one or more of the group
consisting of R.sup.9, R.sup.10, R.sup.11, and R.sup.12, with the
proviso that Q.sup.b is bonded to lowest number substituent
position of each W.sup.5, with the further proviso that Q.sup.b is
bonded to highest number substituent position of each W.sup.6, and
with the additional proviso that (CH(R.sup.38)).sub.r is bonded to
E.sup.0.
22. Compound of claim 21 of the Formula: 103or a pharmaceutically
acceptable salt thereof, wherein; B is phenyl or a heteroaryl of 5
or 6 ring members, wherein a carbon adjacent to the carbon at the
point of attachment of said phenyl or heteroaryl ring to A is
optionally substituted by R.sup.32, the other carbon adjacent to
the carbon at the point of attachment is optionally substituted by
R.sup.36, a carbon adjacent to R.sup.32 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.33, a carbon adjacent to R.sup.36 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.35, and any carbon adjacent to both R.sup.33 and R.sup.35 is
optionally substituted by R.sup.34; R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36 are independently selected from the group
consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy,
hydroxy, amino, alkoxyamino, haloalkanoyl, nitro, alkylamino,
alkylthio, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl,
heterocyclyl, alkylsulfonamido, amidosulfonyl, alkyl, alkenyl,
halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl,
hydroxyhaloalkyl, aminoalkyl,carboalkoxy, carboxy, carboxamido,
cyano, and Q.sup.b; B is optionally selected from the group
consisting of hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl,
C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each
member of group B is optionally substituted at any carbon up to and
including 6 atoms from the point of attachment of B to A with one
or more of the group consisting of R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36; B is optionally a C3-C12 cycloalkyl or a
C4-C9 saturated heterocyclyl, wherein each ring carbon is
optionally substituted with R.sup.33, a ring carbon other than the
ring carbon at the point of attachment of B to A is optionally
substituted with oxo provided that no more than one ring carbon is
substituted by oxo at the same time, ring carbons and a nitrogen
adjacent to the carbon atom at the point of attachment are
optionally substituted with R.sup.9 or R.sup.13, a ring carbon or
nitrogen atom adjacent to the R.sup.9 position and two atoms from
the point of attachment is optionally substituted with R.sup.10, a
ring carbon or nitrogen atom adjacent to the R.sup.13 position and
two atoms from the point of attachment is optionally substituted
with R.sup.12, a ring carbon or nitrogen atom three atoms from the
point of attachment and adjacent to the R.sup.10 position is
optionally substituted with R.sup.11, a ring carbon or nitrogen
atom three atoms from the point of attachment and adjacent to the
R.sup.12 position is optionally substituted with R.sup.33, and a
ring carbon or nitrogen atom four atoms from the point of
attachment and adjacent to the R.sup.11 and R.sup.33 positions is
optionally substituted with R.sup.34; R.sup.9, R.sup.10, R.sup.11,
R.sup.12, and R.sup.13 are independently selected from the group
consisting of hydrido, acetamido, haloacetamido, alkoxyamino,
alkanoyl, haloalkanoyl, amidino, guanidino, alkylenedioxy,
haloalkylthio, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy,
aryloxy, heteroaryloxy, heteroaralkoxy,heterocyclyloxy,
heterocyclylalkoxy, hydroxy, amino, alkylamino,
N-alkyl-N-arylamino, arylamino, aralkylamino, heteroarylamino,
heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino,
alkylthio, alkylsulfinyl, arylsulfinyl, aralkylsulfinyl,
cycloalkylsulfinyl, heteroarylsulfinyl, alkylsulfamido,
alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl,
heteroarylsulfonyl, amidosulfonyl, alkyl, aryl, aralkyl,
cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, halo,
haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl,
carboalkoxy, carboxy, carboxyalkyl, carboxamido, and cyano; A is
bond or (CH(R.sup.15)).sub.pa--(W ).sub.rr wherein rr is 0 or 1, pa
is an integer selected from 0 through 3, and W.sup.7 is selected
from the group consisting of O, S, C(O), (R.sup.7)NC(O),
(R.sup.7)NC(S), and N(R.sup.7), with the proviso that W.sup.7 is
bonded to the N(H) on the 1,4-quinone ring; R.sup.7is selected from
the group consisting of hydrido, hydroxy and alkyl; R.sup.15 is
selected from the group consisting of hydrido, hydroxy, halo,
alkyl, and haloalkyl; X.sup.0 is selected from the group consisting
of hydrido, alkyl, cyano, halo, haloalkyl, haloalkoxy, amino,
aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy,
hydroxyalkyl, alkoxyamino, thiol, and alkylthio; R.sup.2 is
Z.sup.0-Q; Z.sup.0 is selected from the group consisting of a bond,
(CR.sup.41R.sup.42).sub.q wherein q is 1 or 2, and
(CH(R.sup.41)).sub.g--W.sup.0--(CH(R.sup.42)).sub.p wherein g and p
are integers independently selected from 0 through 3 and W.sup.0 is
selected from the group consisting of O, S, C(O), S(O),
N(R.sup.41), and ON(R.sup.41); Z.sup.0 is optionally
(CH(R.sup.41)).sub.e--W.sup.22--(CH(R- .sup.42)).sub.h wherein e
and h are independently 0 or 1 and W.sup.22 is selected from the
group consisting of CR.sup.41.dbd.CR.sup.42, 1,2-cyclopropyl,
1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl,
1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl,
3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl,
2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,
2,3-piperidinyl, 2,4piperidinyl, 2,6-piperidinyl, 3,4piperidinyl,
1,2-pyrrolidinyl,1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2,3-tetrahydrofuranyl, 2,4tetrahydrofuranyl, 2,5-tetrahydrofuranyl,
and 3,4-tetrahydrofuranyl, wherein Z.sup.0 is directly bonded to
the 1,4-quinone ring and W.sup.22 is optionally substituted with
one or more substituents selected from the group consisting of
R.sup.9, R.sup.10, R.sup.11, R.sup.12, and R.sup.13; R.sup.41 and
R.sup.42 are independently selected from the group consisting of
hydrido, hydroxy, alkyl, and amino; Q is phenyl or a heteroaryl of
5 or 6 ring members, wherein a carbon adjacent to the carbon at the
point of attachment of said phenyl or heteroaryl ring to Z.sup.0 is
optionally substituted by R.sup.9, the other carbon adjacent to the
carbon at the point of attachment is optionally substituted by
R.sup.13, a carbon adjacent to R.sup.9 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.10, a carbon adjacent to R.sup.13 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.12, and any carbon adjacent to both R.sup.10 and R.sup.12 is
optionally substituted by R.sup.11; Q is optionally hydrido with
the proviso that Z.sup.0 is other than a bond; K is
CR.sup.4aR.sup.4b; R.sup.4a and R.sup.4b are independently selected
from the group consisting of hydrido, hydroxyalkyl, alkyl,
alkoxyalkyl, alkylthioalkyl, and haloalkyl; E.sup.0, with the
proviso that K is CR.sup.4aR.sup.4b, is E.sup.1 wherein E.sup.1 is
selected from the group consisting of a covalent single bond,
C(O)N(H), (H)NC(O), S(O).sub.2N(H), and N(H)S(O).sub.2; K is
optionally (CH(R.sup.14)).sub.j-T wherein j is 0 or 1 and T is a
bond or N(R.sup.7) with the proviso that (CH(R.sup.14)).sub.j is
bonded to the phenyl ring; R is hydrido or halo; E.sup.0, with the
proviso that K is (CH(R.sup.14)).sub.j-T is E.sup.2 wherein E.sup.2
is selected from the group consisting of C(O)N(H), (H)NC(O),
C(S)N(H), (H)NC(S), S(O).sub.2N(H), N(H)S(O).sub.2,
S(O).sub.2N(H)C(O), and C(O)N(H)S(O).sub.2; Y.sup.0 is phenyl or a
heteroaryl of 5 or 6 ring members, wherein one carbon of said
phenyl or said heteroaryl is substituted by Q.sup.s, a carbon two
or three atoms from the point of attachment of Q.sup.s to said
phenyl or said heteroaryl is substituted by Q.sup.b, a carbon
adjacent to the point of attachment of Q.sup.s is optionally
substituted by R.sup.17, another carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.18, a
carbon adjacent to Q.sup.b is optionally substituted by R.sup.16,
and another carbon adjacent to Q.sup.b is optionally substituted by
R.sup.19; R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are
independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
alkoxyamino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,
alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy,
hydroxyalkyl, aminoalkyl, and cyano; R.sup.16 or R.sup.19 is
optionally selected from the group consisting of NR.sup.20R.sup.21,
N(R.sup.26)C(NR.sup.25)N(R.sup- .23)(R.sup.24), and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido; Q.sup.b is
selected from the group consisting of NR.sup.20R.sup.21, hydrido,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24), and
C(NR.sup.25)NR.sup.23R.- sup.24, with the proviso that no more than
one of R.sup.20 and R.sup.21 is selected from the group consisting
of hydroxy, amino, alkylamino, and dialkylamino at the same time,
with the further proviso that no more than one of R.sup.23 and
R.sup.24 is selected from the group consisting of hydroxy, amino,
alkylamino, and dialkylamino at the same time; R.sup.20, R.sup.21,
R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, alkyl, hydroxy,
amino, alkylamino and dialkylamino; Q.sup.s is selected from the
group consisting of a bond, (CR.sup.37R.sup.38).sub.b wherein b is
an integer selected from 1 through 4, and
(CH(R.sup.14)).sub.c--W.sup.1--(CH(R.sup.1- 5)).sub.d wherein c and
d are integers independently selected from 1 through 3 and W.sup.1
is selected from the group consisting of C(O)N(R.sup.14),
(R.sup.14)NC(O), S(O), S(O).sub.2, S(O).sub.2N(R.sup.14),
N(R.sup.14)S(O).sub.2, and N(R.sup.14), with the proviso that
R.sup.14 is selected from other than halo when directly bonded to
N, and with the additional proviso that (CR.sup.37R.sup.38).sub- .b
and (CR.sup.37R.sup.38).sub.b, and (CH(R.sup.14)).sub.c are bonded
to E.sup.0; R.sup.37 and R.sup.38 are independently selected from
the group consisting of hydrido, alkyl, and haloalkyl; R.sup.38 is
optionally aroyl or heteroaroyl, wherein R.sup.38 is optionally
substituted with one or more substituents selected from the group
consisting of R.sup.16, R.sup.17, R.sup.18, and R.sup.19; Y.sup.0
is optionally Y.sup.AT wherein Y.sup.AT is Q.sup.b-Q.sup.s; Y.sup.0
is optionally Q.sup.b-Q.sup.ss wherein Q.sup.ss is
(CH(R.sup.14)).sub.e--W.sup.2--(CH(R.sup.15)).sub.h, wherein e and
h are independently 1 or 2 and W.sup.2 is CR.sup.4a.dbd.CR.sup.4b
with the proviso that (CH(R.sup.14)).sub.e is bonded to
E.sup.0.
23. Compound of claim 22 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8
alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of
group B is optionally substituted at any carbon up to and including
6 atoms from the point of attachment of B to A with one or more of
the group consisting of R.sup.32, R.sup.33, R.sup.34, R.sup.35, and
R.sup.36; R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy,
amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl,
halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl,
carboalkoxy, carboxy, carboxamido, cyano, and Q.sup.b; A is
(CH(R.sup.15)).sub.pa--W.sup.7 wherein pa is an integer selected
from 0 through 3 and W.sup.7 is selected from the group consisting
of O, S, and N(R.sup.7) wherein R.sup.7 is hydrido or alkyl;
R.sup.15 is selected from the group consisting of hydrido, hydroxy,
halo, alkyl, and haloalkyl; X.sup.0 is selected from the group
consisting of hydrido, alkyl, cyano, halo, haloalkyl, haloalkoxy,
amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino,
alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio; R.sup.2 is
Z.sup.0-Q; Z.sup.0 is a bond or (CR.sup.41R.sup.42).sub.q wherein q
is 1 or 2; R.sup.41 and R.sup.42 are independently selected from
the group consisting of hydrido, hydroxy, and amino; Q is phenyl or
a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to
the carbon at the point of attachment of said phenyl or heteroaryl
ring to Z.sup.0 is optionally substituted by R.sup.9, the other
carbon adjacent to the carbon at the point of attachment is
optionally substituted by R.sup.13, a carbon adjacent to R.sup.9
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.10, a carbon adjacent to R.sup.13
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.12, and any carbon adjacent to both
R.sup.10 and R.sup.12 is optionally substituted by R.sup.11, with
the proviso that Q is other than a phenyl when Z.sup.0 is a bond;
R.sup.9, R.sup.10, R.sup.11, R.sup.12, and R.sup.13 are
independently selected from the group consisting of hydrido,
acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl,
amidino, guanidino, alkylenedioxy, haloalkylthio, alkoxy,
cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy,
heteroaralkoxy,heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino,
alkylamino, N-alkyl-N-arylamino, arylamino, aralkylamino,
heteroarylamino, heteroaralkylamino, heterocyclylamino,
heterocyclylalkylamino, alkylthio, alkylsulfinyl, arylsulfinyl,
aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl,
alkylsulfamido, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl,
cycloalkylsulfonyl, heteroarylsulfonyl, amidosulfonyl, alkyl, aryl,
aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl,
halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl,
aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, and
cyano; K is CHR.sup.4a wherein R.sup.4b is selected from the group
consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl,
alkylthioalkyl, and haloalkyl; E.sup.0 is selected from the group
consisting of a bond, C(O)N(H), (H)NC(O), (R.sup.7)NS(O).sub.2, and
S(O).sub.2N(R.sup.7); Y.sup.0 is phenyl or a heteroaryl of 5 or 6
ring members, wherein one carbon of said phenyl or said heteroaryl
is substituted by Q.sup.s, a carbon two or three contiguous atoms
from the point of attachment of Q.sup.s to the phenyl or heteroaryl
ring is substituted by Q.sup.b, a carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.17,
another carbon adjacent to the point of attachment of Q.sup.s is
optionally substituted by R.sup.18, a carbon adjacent to Q.sup.b is
optionally substituted by R.sup.16, and another carbon adjacent to
Q.sup.b is optionally substituted by R.sup.19; R.sup.16, R.sup.17,
R.sup.18, and R.sup.19 are independently selected from the group
consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,
alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio,
alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo,
haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;
R.sup.16 or R.sup.19 is optionally selected from the group
consisting of NR.sup.20R.sup.21,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24), and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido; Q.sup.b is
selected from the group consisting of NR.sup.20R.sup.21, hydrido,
N(R.sup.26)C(NR.sup.25)N(- R.sup.23)(R.sup.24) and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that no more than
one of R.sup.20 and R.sup.21 is selected from the group consisting
of hydroxy, amino, alkylamino, and dialkylamino at the same time
and with the further proviso that no more than one of R.sup.23 and
R.sup.24 is selected from the group consisting of hydroxy, amino,
alkylamino, and dialkylamino at the same time; R.sup.20, R.sup.21,
R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, alkyl, hydroxy,
amino, alkylamino and dialkylamino; Q.sup.s is selected from the
group consisting of a bond, (CR.sup.37R.sup.38).sub.b wherein b is
an integer selected from 1 through 3, and
(CH(R.sup.14)).sub.c--W.sup.1--(CH(R.sup.15)).sub.d wherein c and d
are independently 1 or 2 and W.sup.1 is selected from the group
consisting of C(O)N(R.sup.14),(R.sup.14)NC(O), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, and N(R.sup.14), with
the proviso that R.sup.14 is selected from other than halo when
directly bonded to N and with the further proviso that
(CR.sup.37R.sup.38).sub.b, and (CH(R.sup.14)).sub.c are bonded to
E.sup.0; R.sup.14 is selected from the group consisting of hydrido,
halo, alkyl, and haloalkyl; R.sup.37 and R.sup.38 are independently
selected from the group consisting of hydrido, alkyl, and
haloalkyl; R.sup.38 is optionally aroyl and heteroaroyl; Y.sup.0 is
optionally Q.sup.b-Q.sup.ss wherein Q.sup.ss is
(CH(R.sup.14)).sub.e--W.sup.2--(CH(R.sup.15)).sub.h, wherein e and
h are integers independently selected from 1 through 2 and W.sup.2
is CR.sup.4a.dbd.CH with the proviso that (CH(R.sup.14)).sub.e is
bonded to E.sup.0.
24. Compound of claim 23 of the Formula: 104or a pharmaceutically
acceptable salt thereof, wherein; B is selected from the group
consisting of hydrido, trialkylsilyl, C2-C4 alkyl, C3-C5 alkylenyl,
C3-C4 alkenyl, C3-C4 alkynyl, and C2-C4 haloalkyl, wherein each
member of group B is optionally substituted at any carbon up to and
including 3 atoms from the point of attachment of B to A with one
or more of the group consisting of R.sup.32, R.sup.33, and
R.sup.34; R.sup.32, R.sup.33, and R.sup.34 are independently
selected from the group consisting of hydrido, acetamido,
haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino,
alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo,
haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboalkoxy,
carboxy, carboxamido, and cyano; A is
(CH(R.sup.15)).sub.pa--N(R.sup.7) wherein pa is an integer selected
from 0 through 2 and R.sup.7 is hydrido or alkyl; R.sup.15 is
selected from the group consisting of hydrido, halo, alkyl, and
haloalkyl; X.sup.0 is selected from the group consisting of
hydrido, alkyl, cyano, halo, haloalkyl, haloalkoxy, amino,
aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy,
hydroxyalkyl, alkoxyamino, thiol, and alkylthio; R.sup.2 is
Z.sup.0-Q; Z.sup.0 is a bond or CH.sub.2; Q is phenyl or a
heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the
carbon at the point of attachment of said phenyl or heteroaryl ring
to Z.sup.0 is optionally substituted by R.sup.9, the other carbon
adjacent to the carbon at the point of attachment is optionally
substituted by R.sup.13, a carbon adjacent to R.sup.9 and two atoms
from the carbon at the point of attachment is optionally
substituted by R.sup.10, a carbon adjacent to R.sup.13 and two
atoms from the carbon at the point of attachment is optionally
substituted by R.sup.12, and any carbon adjacent to both R.sup.10
and R.sup.12 is optionally substituted by R.sup.11; R.sup.9,
R.sup.11, and R.sup.13 are independently selected from the group
consisting of hydrido, hydroxy, amino, amidino, guanidino,
alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl,
alkylsulfonyl, amidosulfonyl, alkyl, alkoxy, halo, haloalkyl,
haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboxy, carboxamido,
and cyano; R.sup.10 and R.sup.12 are independently selected from
the group consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl,
heteroaryl, heterocyclyl, alkoxy, cycloalkoxy, cycloalkylalkoxy,
aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy,
heterocyclylalkoxy, hydroxy, amino, alkoxyamino, alkylamino,
arylamino, aralkylamino, heteroarylamino, heteroaralkylamino,
heterocyclylamino, heterocyclylalkylamino, alkylsulfonamido,
amidosulfonyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl,
heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl,
cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl,
hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl,
carboxamido, halo, haloalkyl, and cyano; Y.sup.0 is phenyl or a
heteroaryl of 5 or 6 ring members, wherein one carbon of said
phenyl or said heteroaryl is substituted by Q.sup.s, a carbon two
or three atoms from the point of attachment of Q.sup.s to said
phenyl or said heteroaryl is substituted by Q.sup.b, a carbon
adjacent to the point of attachment of Q.sup.s is optionally
substituted by R.sup.17, another carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.18, a
carbon adjacent to Q.sup.b is optionally substituted by R.sup.16,
and another carbon adjacent to Q.sup.b is optionally substituted by
R.sup.19; R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are
independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl,
haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,
aminoalkyl, and cyano; R.sup.16 or R.sup.19 is optionally selected
from the group consisting of NR.sup.20R.sup.21,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24), and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido; Q.sup.b is
selected from the group consisting of NR.sup.20R.sup.21, hydrido,
C(NR.sup.25)NR.sup.23R.su- p.24, and
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),with the proviso that
no more than one of R.sup.20 and R.sup.21 is hydroxy at the same
time and with the further proviso that no more than one of R.sup.23
and R.sup.24 is hydroxy at the same time; R.sup.20, R.sup.21,
R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, alkyl, and hydroxy;
Q.sup.s is selected from the group consisting of a bond, CH.sub.2,
and CH.sub.2CH.sub.2.
25. Compound of claim 24 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of ethyl,
2-propenyl, 2-propynyl, propyl, isopropyl,
--CH.sub.2CH.sub.2CH.sub.2--, --CH.sub.2CH.sub.2CH.sub.2CH.sub.2--,
butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, tert-butyl,
isobutyl, 2-methylpropenyl, 2,2,2-trifluoroethyl,
3,3,3-trifluoropropyl, and 2,2-difluoropropyl, wherein each member
of group B is optionally substituted at any carbon up to and
including 3 atoms from the point of attachment of B to A with one
or more of the group consisting of R.sup.32, R.sup.33, and
R.sup.34; R.sup.32, R.sup.33, and R.sup.34 are independently
selected from the group consisting of hydrido, amidino, guanidino,
carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,
methoxyamino, ethoxyamino, acetamido, trifluoroacetamido,
N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio,
isopropylthio, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy,
fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl,
N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,
2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl,
ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,
N,N-dimethylamidocarbonyl, and cyano; A is selected from the group
consisting of a bond, NH, and N(CH.sub.3); X.sup.0 is selected from
the group consisting of hydrido, hydroxy, amino, amidino,
hydroxyamino, aminomethyl, 1-aminoethyl, methylamino,
dimethylamino, cyano, methyl, ethyl, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio,
ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro,
chloro, and bromo; R is Z.sup.0-Q; Z.sup.0 is a bond or CH.sub.2; Q
is selected from the group consisting of phenyl, 2-thienyl,
3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,
4-imidazolyl, 3-pyrazolyl, 4pyrazolyl, 2-thiazolyl, 3-isoxazolyl,
5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4pyridyl, 2-pyrazinyl,
2-pyrimidinyl, 4pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,
4pyridazinyl, and 1,3-triazin-2-yl, wherein a carbon adjacent to
the carbon at the point of attachment of said phenyl or heteroaryl
ring to Z.sup.0 is optionally substituted by R.sup.9, the other
carbon adjacent to the carbon at the point of attachment is
optionally substituted by R.sup.13, a carbon adjacent to R.sup.9
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.10, a carbon adjacent to R.sup.13
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.12, and any carbon adjacent to both
R.sup.10 and R.sup.12 is optionally substituted by R.sup.11;
R.sup.9, R.sup.11, and R.sup.13 are independently selected from the
group consisting of hydrido, amidino, guanidino, carboxy, methyl,
ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy,
hydroxy, amino, N-methylamino, N,N-dimethylamino, N-ethylamino,
methylthio, ethylthio, isopropylthio, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl,
N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,
2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;
R.sup.10 and R.sup.12 are independently selected from the group
consisting of hydrido, amidino, guanidino, carboxy, carboxymethyl,
methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy,
propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido,
trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,
N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,
amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,
amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl,
N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl,
N-(3-fluorobenzyl)amidocarbonyl,
N-(2-trifluoromethylbenzyl)amidocarbonyl- ,
N-(1-phenylethyl)amidocarbonyl,
N-(1-methyl-1-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl,
N-(2-chlorobenzyl)amidosulfonyl, N-isopropylamidocarbonyl,
N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl, fluoro,
chloro, bromo, cyano, cyclobutoxy, cyclohexoxy, cyclohexylmethoxy,
4-trifluoromethycyclohexylmethoxy, cyclopentoxy, benzyl, benzyloxy,
4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy,
4-bromobenzylamino, 5-bromopyrid-2-ylmethylamino,
4-butoxyphenamino, 3-chlorobenzyl, 4-chlorophenoxy,
4-chloro-3-ethylphenoxy, 4-chloro-3-ethylbenzylamino,
4-chloro-3-ethylphenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy,
4-chlorobenzylsulfonyl, 4-chlorophenylamino,
4-chlorophenylsulfonyl, 5-chloropyrid-3-yloxy,
2-cyanopyrid-3-yloxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy,
3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorophenoxy,
3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy,
2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy,
3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyloxy,
3,5-dimethylbenzyloxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy,
3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy,
4-fluorobenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy,
3-fluoro-5-trifluoromethylbenzyloxy,
4-fluoro-2-trifluoromethylbenzyloxy,
4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy,
4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy,
2-fluorobenzyloxy, 4-fluorophenylamino,
2-fluorotrifluoromethylphenoxy, 4-isopropylbenzyloxy,
3-isopropylphenoxy, 4-isopropylphenoxy,
4-isopropyl-3-methylphenoxy, 4-isopropylbenzyloxy,
3-isopropylphenoxy, 4-isopropylphenoxy,
4-isopropyl-3-methylphenoxy, phenylamino, 1-phenylethoxy,
2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino, phenylsulfonyl,
3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy,
3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy,
3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy,
2,4-bis-trifluoromethylbenzyloxy, 3-trifluoromethylbenzyl, 3,
-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy,
3-trifluoromethylphenoxy, 3-trifluoromethylthiobenzyloxy,
4-trifluoromethylthiobenzyloxy, 2,3,4-trifluorophenoxy,
2,3,5-trifluorophenoxy, 3-pentafluoroethylphenoxy,
3-(1,1,2,2-tetrafluoroethoxy)phenoxy, and
3-trifluoromethylthiophenoxy; Y.sup.0 is selected from the group
consisting of: 1-Q.sup.b-4-Q.sup.s-2-R-
.sup.16-3-R.sup.17-5-R.sup.18-6-R.sup.19 benzene,
2-Q.sup.b-5-Q.sup.s-6-R.- sup.17-4-R.sup.18-3-R.sup.19 pyridine,
3-Q.sup.b-6-Q.sup.s-2-R.sup.16-5-R.- sup.18- 4-R.sup.19 pyridine,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-6-R.sup.18 pyrazine,
3-Q.sup.b-6-Q.sup.s-2-R.sup.18-5-R.sup.18-4-R.sup.19 pyridazine,
2-Q.sup.b-5-Q.sup.s-4-R.sup.17-6-R.sup.18 pyrimidine,
5-Q.sup.b-2-Q.sup.s-4-R.sup.16-6-R.sup.19 pyrimidine
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 thiophene,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 thiophene,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 furan,
2-Q.sup.b-5-Q.sup.s-3-R.- sup.16-4-R.sup.17 furan,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 pyrrole,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-4-R.sup.17 pyrrole,
4-Q.sup.b-2-Q.sup.s-5-R.sup.19 imidazole,
2-Q.sup.b-4-Q.sup.s-5-R.sup.17 imidazole,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16 isoxazole,
5-Q.sup.b-3-Q.sup.s-4-R.sup.16 isoxazole,
2-Q.sup.b-5-Q.sup.s-4-R.sup.16 pyrazole,
4-Q.sup.b-2-Q.sup.s-5-R.sup.19 thiazole, and
2-Q.sup.b-5-Q.sup.s-4-R.sup.17 thiazole; R.sup.16, R.sup.17,
R.sup.18, and R.sup.19 are independently selected from the group
consisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy,
amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy,
amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,
dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,
trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,
ethylsulfonyl, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, and cyano; R.sup.16
or R.sup.19 is optionally selected from the group consisting of
NR.sup.20R.sup.21, N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup- .24),
and C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido; Q.sup.b is
selected from the group consisting of NR.sup.20R.sup.21, hydrido,
C(NR.sup.25)NR.sup.23R.sup.24, and
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.s- up.24),with the proviso
that no more than one of R.sup.20, R.sup.21, R.sup.23, and R.sup.24
can be hydroxy, when any two of the group consisting of R.sup.20,
R.sup.21, R.sup.23, and R.sup.24 are bonded to the same atom and
with the further proviso that said Q.sup.b group is bonded directly
to a carbon atom; R.sup.20, R.sup.21, R.sup.23, R.sup.24, R.sup.25,
and R.sup.26 are independently selected from the group consisting
of hydrido, methyl, ethyl, propyl, butyl, isopropyl, and hydroxy;
Q.sup.s is selected from the group consisting of a bond, CH.sub.2,
and CH.sub.2CH.sub.2.
26. Compound of claim 24 of the Formula: 105or a pharmaceutically
acceptable salt thereof, wherein; A is selected from the group
consisting of CH.sub.2N(CH.sub.3), CH.sub.2N(CH.sub.2CH.sub.3),
CH.sub.2CH.sub.2N(CH.sub.3), and
CH.sub.2CH.sub.2N(CH.sub.2CH.sub.3); X.sup.o is selected from the
group consisting of hydrido, hydroxy, amino, amidino, hydroxyamino,
aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano,
methyl, ethyl, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl,
2-hydroxyethyl, methoxyamino, methylthio, ethylthio,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and
bromo; R.sup.2 is Z.sup.0-Q; Z.sup.0 is a bond or CH.sub.2; Q is
selected from the group consisting of phenyl, 2-thienyl, 3-thienyl,
2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,
4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl,
5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl,
2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,
4-pyridazinyl, and 1,3,5triazin-2-yl, wherein a carbon adjacent to
the carbon at the point of attachment of said phenyl or heteroaryl
ring to Z.sup.0 is optionally substituted by R.sup.9, the other
carbon adjacent to the carbon at the point of attachment is
optionally substituted by R.sup.13, a carbon adjacent to R.sup.9
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.10, a carbon adjacent to R.sup.13
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.12, and any carbon adjacent to both
R.sup.10 and R.sup.12 is optionally substituted by R.sup.11;
R.sup.9, R.sup.11, and R.sup.13 are independently selected from the
group consisting of hydrido, amidino, guanidino, carboxy, methyl,
ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy,
hydroxy, amino, N-methylamino, N,N-dimethylamino, N-ethylamino,
methylthio, ethylthio, isopropylthio, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl,
N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,
2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;
R.sup.10 and R.sup.12 are independently selected from the group
consisting of hydrido, amidino, guanidino, carboxy, carboxymethyl,
methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy,
propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido,
trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,
N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,
amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,
amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl,
N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl,
N-(3-fluorobenzyl)amidocarbonyl,
N-(2-trifluoromethylbenzyl)amidocarbonyl- ,
N-(1-phenylethyl)amidocarbonyl,
N-(1-methyl-1-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl,
N-(2-chlorobenzyl)amidosulfonyl, N-isopropylamidocarbonyl,
N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl, fluoro,
chloro, bromo, cyano, cyclobutoxy, cyclohexoxy, cyclohexylmethoxy,
4-trifluoromethycyclohexylmethoxy, cyclopentoxy, benzyl, benzyloxy,
4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy,
4-bromobenzylamino,. 5-bromopyrid-2-ylmethylamino,
4-butoxyphenamino, 3-chlorobenzyl, 4-chlorophenoxy,
4-chloro-3-ethylphenoxy, 4-chloro-3-ethylbenzylamino,
4-chloro-3-ethylphenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy,
4-chlorobenzylsulfonyl, 4-chlorophenylamino,
4-chlorophenylsulfonyl, 5-chloropyrid-3-yloxy,
2-cyanopyrid-3-yloxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy,
3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorophenoxy,
3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy,
2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy,
3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyloxy,
3,5-dimethylbenzyloxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy,
3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy,
4-fluorobenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy,
3-fluoro-5-trifluoromethylbenzyloxy,
4-fluoro-2-trifluoromethylbenzyloxy,
4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy,
4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy,
2-fluorobenzyloxy, 4-fluorophenylamino,
2-fluorotrifluoromethylphenoxy, 4-isopropylbenzyloxy,
3-isopropylphenoxy, 4-isopropylphenoxy, 4-isopropyl
-3-methylphenoxy, 4-isopropylbenzyloxy, 3-isopropylphenoxy,
4-isopropylphenoxy, 4-isopropyl-3-methylphenoxy, phenylamino,
1-phenylethoxy, 2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino,
phenylsulfonyl, 3-trifluoromethoxybenzyloxy,
4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy,
4-trifluoromethoxyphenoxy, 3-trifluoromethylbenzyloxy,
4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy,
3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy,
4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy,
3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy,
2,3,4-trifluorophenoxy, 2,3,5-trifluorophenoxy,
3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy,
and 3-trifluoromethylthiophenoxy; Y.sup.0 is selected from the
group consisting of: 1-Q.sup.b-4-Q.sup.s-2-R-
.sup.16-3-R.sup.17-5-R.sup.18-6-R.sup.19 benzene,
2-Q.sup.b-5-Q.sup.s-6-R.- sup.17-4-R.sup.18-3-R.sup.19 pyridine,
3-Q.sup.b-6-Q.sup.s-2-R.sup.16-5-R.- sup.18-4-R.sup.19 pyridine,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-6-R.sup.18 pyrazine,
3-Q.sup.b-6-Q.sup.s-2-R.sup.18-5-R.sup.18-4-R.sup.19 pyridazine,
2-Q.sup.b-5-Q.sup.s-4-R.sup.17-6-R.sup.18 pyrimidine,
5-Q.sup.b-2-Q.sup.s-4-R.sup.16-6-R.sup.19 pyrimidine,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 thiophene,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 thiophene,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 furan,
2-Q.sup.b-5-Q.sup.s-3-R.- sup.16-4-R.sup.17 furan,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 pyrrole,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 pyrrole,
4-Q.sup.b-2-Q.sup.s-5-R.sup.19 imidazole,
2-Q.sup.b-4-Q.sup.s-5-R.sup.17 imidazole,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16 isoxazole,
5-Q.sup.b-3-Q.sup.s-4-R.sup.16 isoxazole,
2-Q.sup.b-5-Q.sup.s-4-R.sup.16 pyrazole,
4-Q.sup.b-2-Q.sup.s-5-R.sup.19 thiazole, and
2-Q.sup.b-5-Q.sup.s-4R.sup.17 thiazole; R.sup.16, R.sup.17,
R.sup.18, and R.sup.19 are independently selected from the group
consisting of hydrido, methyl, ethyl, isopropyl, propyl, amidino,
guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,
aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,
dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,
trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,
ethylsulfonyl, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, and cyano; Q.sup.b
is selected from the group consisting of NR.sup.20R.sup.21,
C(NR.sup.25)NR.sup.23R.sup.24, and
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.s- up.24), with the proviso
that no more than one of R.sup.20, R.sup.21, R.sup.23 and R.sup.24
can be hydroxy, when any two of the group consisting of R.sup.20,
R.sup.21, R.sup.23, and R.sup.24 are bonded to the same atom, and
with the further proviso that said Q.sup.b group is bonded directly
to a carbon atom; R.sup.20, R.sup.21, R.sup.23, R.sup.24, R.sup.25,
and R.sup.26 are independently selected from the group consisting
of hydrido, methyl, ethyl, propyl, butyl, isopropyl, and hydroxy;
Q.sup.s is selected from the group consisting of a bond, CH.sub.2,
and CH.sub.2CH.sub.2.
27. Compound of claim 26 or a pharmaceutically acceptable salt
thereof, wherein; A is selected from the group consisting of
CH.sub.2N(CH.sub.3), CH.sub.2N(CH.sub.2CH.sub.3),
CH.sub.2CH.sub.2N(CH.sub.3), and
CH.sub.2CH.sub.2N(CH.sub.2CH.sub.3); X.sup.o is selected from the
group consisting of hydrido, hydroxy, amino, amidino, hydroxyamino,
aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy,
hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro,
and chloro; R.sup.2 is Z.sup.0-Q; Z.sup.0 is a bond or CH.sub.2; Q
is selected from the group consisting of
3-amidocarbonyl-5-aminophenyl,
3-amino-5-(N-benzylamidocarbonyl)phenyl, 3-amino-5-benzylphenyl,
3-amino-5-(2-phenylethyl)phenyl, 3-amino-5-benzylaminophenyl,
3-amino-5-(2-phenylethylamino)phenyl, 3-amino-5-benzyloxyphenyl,
3-amino-5-(2-phenylethoxy)phenyl, 3-amino-5-(N-(2-chlorobenzyl
)amidocarbonyl)phenyl,
3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-methyl-- 1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-benzylamidosulfonyl)pheny- l,
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl,
3-amino-5-(N-ethylamidocarbonyl)phenyl,
3-amino-5-(N-isopropylamidocarbon- yl)phenyl,
3-amino-5-(N-propylaminocarbonyl)phenyl,
3-amino-5-(N-isobutylamidocarbonyl)phenyl,
3-amino-5-(N-(2-butyl)amidocar- bonyl)phenyl,
3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,
3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,
3-amino-5-(N-cyclohexylamid- ocarbonyl)phenyl,
5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl,
5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl,
3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl,
3-carboxyphenyl, 3-carboxy-5-hydroxyphenyl,
3-amino-5-carboxyphenyl, 3-chlorophenyl, 2-chlorophenyl,
3-cyanophenyl, 3,5diaminophenyl, 3-dimethylaminophenyl,
2-fluorophenyl, 3-fluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,
3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,
3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,
3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl,
4-methylphenyl, phenyl, 3-trifluoroacetamidophenyl,
3-trifluoromethylphenyl, 2-trifluoromethylphenyl,
5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl,
4-pyridyl, 2-thienyl, and 3-thienyl; Y.sup.0 is selected from the
group consisting of: 1-Q.sup.b-4-Q.sup.s-2-R-
.sup.16-3-R.sup.17-5-R.sup.18-6-R.sup.19 benzene,
2-Q.sup.b-5-Q.sup.s-6-R.- sup.17-4-R.sup.18-3-R.sup.19 pyridine,
3-Q.sup.b-6-Q.sup.s-2-R.sup.16-5-R.- sup.18-4-R.sup.19 pyridine,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 thiophene, and
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 thiophene; R.sup.16 and
R.sup.19 are independently selected from the group consisting of
hydrido, amidino, amino, aminomethyl, methoxy, methylamino,
hydroxy, hydroxymethyl, fluoro, chloro, and cyano; R.sup.17 and
R.sup.18 are independently selected from the group consisting of
hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy,
and cyano; Q.sup.b is C(NR.sup.25)NR.sup.23R.sup.24; R.sup.23,
R.sup.24, and R.sup.25 are independently selected from the group
consisting of hydrido and methyl; Q.sup.s is CH.sub.2.
28. A compound as recited in claim 27 or a pharmaceutically
acceptable salt thereof where said compound is selected from the
group consisting of:
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-aminophenyl]-6-[N,N-d-
imethylhydrazino]-1,4-benzoquinonyl]]acetamide;
2-[2-[N-[[4aminoiminomethy-
lphenyl]methyl]-3-[3-aminophenyl]-6-[N-ethyl-N-methylhydrazino]-1,4-benzoq-
uinonyl]]acetamide;
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-aminop-
henyl]-5-chloro-6-[N,N-dimethylhydrazino]-1,4-benzoquinonyl]]acetamide;
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-aminophenyl]-5-chloro-6-[-
N-ethyl-N-methylhydrazino]-1,4-benzoquinonyl]]acetamide;
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3,5-diaminophenyl]-6-[N,N-d-
imethylhydrazino]-1,4-benzoquinonyl]]acetamide;
2-[2-[N-[[4-aminoiminometh-
ylphenyl]methyl]-3-[3,5-diaminophenyl]-6-[N-ethyl-N-methylhydrazino]-1,4-b-
enzoquinonyl]]acetamide;
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3,5-
-diaminophenyl]-5-chloro-6-[N,N-dimethylhydrazino]-1,4-benzoquinonyl]]acet-
amide;
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3,5-diaminophenyl]-5--
chloro-6-[N-ethyl-N-methylhydrazino]-1,4-benzoquinonyl]]acetamide;
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-
carboxyphenyl]-6-[N,N-dimethylhydrazino]-1,4-benzoquinonyl]]acetamide;
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-carboxyphenyl]-6--
[N-ethyl-N-methylhydrazino]-1,4-benzoquinonyl]]acetamide;
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-carboxyphenyl]-5--
chloro-6-[N,N-dimethylhydrazino]-1,4-benzoquinonyl]]acetamide;
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-carboxyphenyl]-5--
chloro-6-[N-ethyl -N-methylhydrazino]-1,4-benzoquinonyl]]acetamide;
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-(N-benzylamidocar-
bonyl)phenyl]-3-6-[N,N-dimethylhydrazino
1,4-benzoquinonyl]]acetamide;
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-(N-benzylamidocar-
bonyl)phenyl]-6-[N-ethyl-N-methylhydrazino]-1,4-benzoquinonyl]]acetamide;
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-(N-benzylamidocar-
bonyl)phenyl]-5-chloro-6-[N,N-dimethylhydrazino]-1,4-benzoquinonyl]]acetam-
ide;
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-(N-benzylamid-
ocarbonyl)phenyl]-5-chloro-6-[N-ethyl-N-methylhydrazino]-1,4-benzoquinonyl-
]]acetamide.
29. Compound of claim 22 or a pharmaceutically acceptable salt
thereof, wherein; 106or a pharmaceutically acceptable salt thereof,
wherein; B is phenyl or a heteroaryl of 5 or 6 ring members,
wherein a carbon adjacent to the carbon at the point of attachment
of said phenyl or heteroaryl ring to A is optionally substituted by
R.sup.32, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.36, a carbon adjacent
to R.sup.32 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.33, a carbon adjacent
to R.sup.36 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.35, and any carbon
adjacent to both R.sup.33 and R.sup.35 is optionally substituted by
R.sup.34; R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy,
amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl,
halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl,
carboalkoxy, carboxy, carboxamido, cyano, and Q.sup.b; A is a bond
or (CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr wherein rr is 0 or 1, pa
is an integer selected from 0 through 3, and W is (R.sup.7)NC(O) or
N(R.sup.7); R.sup.7 is selected from the group consisting of
hydrido, hydroxy and alkyl; R.sup.15 is selected from the group
consisting of hydrido, halo, alkyl, and haloalkyl; X.sup.o is
selected from the group consisting of hydrido, hydroxy,
hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl,
alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl,
haloalkoxy, and halo; R.sup.2 is Z.sup.0-Q; Z.sup.0 is selected
from the group consisting of a bond, CH.sub.2, CH.sub.2CH.sub.2,
W.sup.0--(CH(R.sup.42)).sub.p wherein p is 0 or 1 and W.sup.0 is
selected from the group consisting of O, S, and N(R.sup.41);
R.sup.41 and R.sup.42 are independently hydrido or alkyl; Q is
phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon
adjacent to the carbon at the point of attachment of said phenyl or
heteroaryl ring to Z.sup.0 is optionally substituted by R.sup.9,
the other carbon adjacent to the carbon at the point of attachment
is optionally substituted by R.sup.13, a carbon adjacent to R.sup.9
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.10, a carbon adjacent to R.sup.13
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.12, and any carbon adjacent to both
R.sup.10 and R.sup.12 is optionally substituted by R.sup.11;
R.sup.9, R.sup.11, and R.sup.13 are independently selected from the
group consisting of hydrido, hydroxy, amino, amidino, guanidino,
alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl,
alkylsulfonyl, amidosulfonyl, alkyl, alkoxy, halo, haloalkyl,
haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboxy, carboxamido,
and cyano; R.sup.10 and R.sup.12 are independently selected from
the group consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl,
heteroaryl, heterocyclyl, alkoxy, cycloalkoxy, cycloalkylalkoxy,
aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy,heterocyclyloxy,
heterocyclylalkoxy, hydroxy, amino, alkoxyamino, alkylamino,
arylamino, aralkylamino, heteroarylamino, heteroaralkylamino,
heterocyclylamino, heterocyclylalkylamino, alkylsulfonamido,
amidosulfonyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl,
heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl,
cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl,
hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl,
carboxamido, halo, haloalkyl, and cyano; Y.sup.0 is phenyl or a
heteroaryl of 5 or 6 ring members, wherein one carbon of said
phenyl or said heteroaryl is substituted by Q.sup.s, a carbon two
or three atoms from the point of attachment of Q.sup.s to said
phenyl or said heteroaryl is substituted by Q.sup.b, a carbon
adjacent to the point of attachment of Q.sup.s is optionally
substituted by R.sup.17, another carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.18, a
carbon adjacent to Q.sup.b is optionally substituted by R.sup.16,
and another carbon adjacent to Q.sup.b is optionally substituted by
R.sup.19; R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are
independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl,
haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,
aminoalkyl, and cyano; R.sup.16 or R.sup.19 is optionally
NR.sup.20R.sup.21 or C(NR.sup.25)NR.sup.23R.sup.24, with the
proviso that R.sup.16, R.sup.19and Q.sup.b are not simultaneously
hydrido; Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, hydrido, and C(NR.sup.25)NR.sup.23, R.sup.24,
with the proviso that no more than one of R.sup.20 and R.sup.21 is
hydroxy at the same time and with the further proviso that no more
than one of R.sup.23 and R.sup.24 is hydroxy at the same time;
R.sup.20, R.sup.21, R.sup.23, R.sup.24, and R.sup.25 are
independently selected from the group consisting of hydrido, alkyl,
and hydroxy; Q.sup.s is selected from the group consisting of a
bond, CH.sub.2, and CH.sub.2CH.sub.2
30. Compound of claim 29 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl,
3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl,
2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl,
4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl,
5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and
1,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at the
point of attachment of said phenyl or heteroaryl ring to A is
optionally substituted by R.sup.32, the other carbon adjacent to
the carbon at the point of attachment is optionally substituted by
R.sup.36, a carbon adjacent to R.sup.32 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.33, a carbon adjacent to R.sup.36 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.35, and any carbon adjacent to both R.sup.33 and R.sup.35 is
optionally substituted by R.sup.34; R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36 are independently selected from the group
consisting of hydrido, amidino, guanidino, carboxy, methoxy,
ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino,
ethoxyamino, acetamido, trifluoroacetamido, N-methylamino,
dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,
N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxye- thyl,
methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and
Q.sup.b; A is selected from the group consisting of a bond, NH,
N(CH.sub.3), N(OH), CH.sub.2, CH.sub.3CH, CF.sub.3CH, NHC(O),
N(CH.sub.3)C(O), C(O)NH, C(O)N(CH.sub.3), CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2, CH.sub.3CHCH.sub.2, and
CF.sub.3CHCH.sub.2; X.sup.o is selected from the group consisting
of hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl,
1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino,
methylthio, ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy,
fluoro, chloro, and bromo; R.sup.2 is Z.sup.0-Q; Z.sup.0 is
selected from the group consisting of a bond, CH.sub.2,
CH.sub.2CH.sub.2, O S, NH, N(CH.sub.3), OCH.sub.2, SCH.sub.2,
N(H)CH.sub.2, and N(CH.sub.3)CH.sub.2; Q is selected from the group
consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl,
2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl,
4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl,
3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl,
5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and
1,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at the
point of attachment of said phenyl or heteroaryl ring to Z.sup.0 is
optionally substituted by R.sup.9, the other carbon adjacent to the
carbon at the point of attachment is optionally substituted by
R.sup.13, a carbon adjacent to R.sup.9 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.10, a carbon adjacent to R.sup.13 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.12, and any carbon adjacent to both R.sup.10 and R.sup.12 is
optionally substituted by R.sup.11; R.sup.9, R.sup.11, and R.sup.13
are independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl,
methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,
N-methylamino, N,N-dimethylamino, N-ethylamino, methylthio,
ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl,
N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,
2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;
R.sup.10 and R.sup.12 are independently selected from the group
consisting of hydrido, amidino, guanidino, carboxy, carboxymethyl,
methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy,
propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido,
trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,
N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,
amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,
amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl,
N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl,
N-(3-fluorobenzyl)amidocarbonyl,
N-(2-trifluoromethylbenzyl)amidocarbonyl- ,
N-(1-phenylethyl)amidocarbonyl,
N-(1-methyl-1-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl,
N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl,
N-isopropylamidocarbonyl, N-propylamidocarbonyl,
N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,
N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl,
N-cyclohexylamidocarbonyl, fluoro, chloro, bromo, cyano,
cyclobutoxy, cyclohexoxy, cyclohexylmethoxy,
4-trifluoromethycyclohexylmethoxy, cyclopentoxy, benzyl, benzyloxy,
4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy,
4-bromobenzylamino, 5-bromopyrid-2-ylmethylamino,
4-butoxyphenamino, 3-chlorobenzyl, 4-chlorophenoxy,
4-chloro-3-ethylphenoxy, 4-chloro-3-ethylbenzylamino,
4-chloro-3-ethylphenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy,
4-chlorobenzylsulfonyl, 4-chlorophenylamino,
4-chlorophenylsulfonyl, 5-chloropyrid-3-yloxy,
2-cyanopyrid-3-yloxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy,
3,4-difluorobenzyloxy, 2,-difluorobenzyloxy, 3,5-difluorophenoxy,
3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy,
2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy,
5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyloxy,
3,5-dimethylbenzyloxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy,
3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy,
4-fluorobenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy,
3-fluoro-5-trifluoromethylbenzyloxy,
4-fluoro-2-trifluoromethylbenzyloxy,
4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy,
4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy,
2-fluorobenzyloxy, 4-fluorophenylamino,
2-fluorotrifluoromethylphenoxy, 4-isopropylbenzyloxy,
3-isopropylphenoxy, 4-isopropylphenoxy,
4-isopropyl-3-methylphenoxy, 4-isopropylbenzyloxy,
3-isopropylphenoxy, 4-isopropylphenoxy,
4-isopropyl-3-methylphenoxy, phenylamino, 1-phenylethoxy,
2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino, phenylsulfonyl,
3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy,
3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy,
3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy,
2,4-bis-trifluoromethylbenzyloxy, 3-trifluoromethylbenzyl,
3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy,
3-trifluoromethylphenoxy, 3-trifluoromethylthiobenzyloxy,
4-trifluoromethylthiobenzyloxy, 2,3,4-trifluorophenoxy,
2,3,5-trifluorophenoxy, 3-pentafluoroethylphenoxy,
3-(1,1,2,2-tetrafluoroethoxy)phenoxy, and
3-trifluoromethylthiophenoxy; Y.sup.0 is selected from the group
consisting of: 1-Q.sup.b-4-Q.sup.s-2-R-
.sup.16-3-R.sup.17-5-R.sup.18-6-R.sup.19 benzene,
2-Q.sup.b-5-Q.sup.s-6-R.- sup.17-4-R.sup.18-3-R.sup.19 pyridine,
3-Q.sup.b-6-Q.sup.s-2-R.sup.16-5-R.- sup.18-4R.sup.19 pyridine,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-6-R.sup.18 pyrazine,
3-Q.sup.b-6-Q.sup.s-2-R.sup.18-5-R.sup.18-4-R.sup.19 pyridazine,
2-Q.sup.b-5-Q.sup.s-4-R.sup.17-6-R.sup.18 pyrimidine,
5-Q.sup.b-2-Q.sup.s-4-R.sup.16-6-R.sup.19 pyrimidine,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 thiophene,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4R.sup.17 thiophene,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 furan,
2-Q.sup.b-5-Q.sup.s-3-R.- sup.16-4R.sup.19 furan,
3-Q.sup.b-5-Q.sup.s-4R.sup.16-2-R.sup.19 pyrrole,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 pyrrole,
4-Q.sup.b-2-Q.sup.s-5-R.sup.19 imidazole,
2-Q.sup.b-4-Q.sup.s-5-R.sup.17 imidazole,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16 isoxazole,
5-Q.sup.b-3-Q.sup.s-4-R.sup.16 isoxazole,
2-Q.sup.b-5-Q.sup.s-4-R.sup.16 pyrazole,
4-Q.sup.b-2-Q.sup.s-5-R.sup.19 thiazole, and
2-Q.sup.b-5-Q.sup.s-4-R.sup.17 thiazole; R.sup.16, R.sup.17,
R.sup.18, and R.sup.19 are independently selected from the group
consisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy,
amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy,
amino, aminomethyl, l-aminoethyl, 2-aminoethyl, N-methylamino,
dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,
trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,
ethylsulfonyl, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, and cyano; R.sup.16
or R.sup.19 is optionally C(NR.sup.25)NR.sup.23R.sup.24 with the
proviso that R.sup.16, R.sup.19, and Q.sup.b are not simultaneously
hydrido; Q.sup.b is C(NR.sup.25)NR.sup.23R.sup.24 or hydrido, with
the proviso that no more than one of R.sup.23 and R.sup.24 is
hydroxy at the same time; R.sup.23, R.sup.24, and R.sup.25 are
independently selected from the group consisting of hydrido,
methyl, ethyl, and hydroxy; Q.sup.s is selected from the group
consisting of a bond, CH.sub.2 and CH.sub.2CH.sub.2.
31. Compound of claim 30 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
2-aminophenyl, 3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl,
3-carboxyphenyl, 3-carboxy-5-hydroxyphenyl, 3-chlorophenyl,
4-chlorophenyl, 3,4dichlorophenyl, 2-fluorophenyl, 3-fluorophenyl,
3,4-difluorophenyl, 3-hydroxyphenyl, 4hydroxyphenyl,
3-methoxyaminophenyl, 3-methoxyphenyl, 4-methoxyphenyl,
3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoromethylphenyl,
2-imidazoyl, 2-pyridyl, 3-pyridyl,
5-chloro-3-trifluoromethyl-2-pyridyl, 4-pyridyl, 2-thienyl,
3-thienyl, and 3-trifluoromethyl-2-pyridyl; A is selected from the
group consisting of CH.sub.2, CH.sub.3CH, CF.sub.3CH, NHC(O),
CH.sub.2CH.sub.2, and CH.sub.2CH.sub.2CH.sub.2; X.sup.o is selected
from the group consisting of hydrido, hydroxy, amino, amidino,
hydroxyamino, aminomethyl, methylamino, cyano, methyl,
trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio,
trifluoromethoxy, fluoro, and chloro; R.sup.2 is Z.sup.0-Q; Z.sup.0
is selected from the group consisting of a bond, CH.sub.2, O, S,
NH, N(CH.sub.3), OCH.sub.2, and SCH.sub.2; Q is selected from the
group consisting of 3-amidocarbonyl-5aminophenyl,
3-amino-5-(N-benzylamidocarbonyl)phenyl, 3-amino-5-benzylphenyl,
3-amino-5-(2-phenylethyl)phenyl, 3-amino-5-benzylaminophenyl,
3-amino-5-(2-phenylethylamino)phenyl, 3-amino-5-benzyloxyphenyl,
3-amino-5-(2-phenylethoxy)phenyl,
3-amino-5-(N-(2-chlorobenzyl)amidocarbo- nyl)phenyl,
3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-methyl-- 1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-benzylamidosulfonyl)pheny- l,
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl,
3-amino-5-(N-ethylamidocarbonyl)phenyl,
3-amino-5-(N-isopropylamidocarbon- yl)phenyl,
3-amino-5-(N-propylamidocarbonyl)phenyl, 3-amino-5-(N-isobutyl
amidocarbonyl)phenyl, 3-amino-5-(N-(2-butyl)amidocarbonyl)phenyl,
3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,
3-amino-5-(N-cyclopentylamid- ocarbonyl)phenyl,
3-amino-5-(N-cyclohexylamidocarbonyl)phenyl, 5amino-2-fluorophenyl,
3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl,
3-amidinophenyl, 3-amino-2-methylphenyl,
5-amino-2-methylthiophenyl, 3-aminophenyl,
3-amino-5-(4-trifluoromethylbe- nzylamino)phenyl,
3-amino-5-(4-trifluoromethylbenzyloxy)phenyl, 3-carboxyphenyl,
3-carboxy-5-hydroxyphenyl, 3-amino-5-carboxyphenyl, 3-chlorophenyl,
2-chlorophenyl, 3-cyanophenyl, 3,5-diaminophenyl,
3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,
2-hydroxyphenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl,
2-methoxyphenyl, 3-methoxyphenyl, 3-methoxyaminophenyl,
3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl,
2-methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl,
3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl,
2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl,
3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl;
Y.sup.0 is selected from the group consisting of:
1-Q.sup.b-4-Q.sup.s-2-R.sup.16-3-R.sup.17-5-R.sup.18-6-R.sup.19
benzene, 2-Q.sup.b-5-Q.sup.s-6-R.sup.17-4-R.sup.18-3-R.sup.19
pyridine, 3-Q.sup.b-6-Q.sup.s-2-R.sup.16-5-R.sup.18-4-R.sup.19
pyridine, 3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 thiophene, and
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 thiophene; R.sup.16 and
R.sup.19 are independently selected from the group consisting of
hydrido, amidino, amino, aminomethyl, methoxy, methylamino,
hydroxy, hydroxymethyl, fluoro, chloro, and cyano; R.sup.16 or
R.sup.19 is optionally C(NR.sup.25)NR.sup.23R.sup.24 with the
proviso that R.sup.16, R.sup.19, and Q.sup.b are not simultaneously
hydrido; R.sup.17 and R.sup.18 are independently selected from the
group consisting of hydrido, fluoro, chloro, hydroxy,
hydroxymethyl, amino, carboxy, and cyano; Q.sup.b is
C(NR.sup.25)NR.sup.23R.sup.24 or hydrido; R.sup.23, R.sup.24, and
R.sup.25 are independently hydrido or methyl; Q.sup.s is
CH.sub.2.
32. Compound of claim 29 of the Formula: 107or a pharmaceutically
acceptable salt thereof, wherein; B is phenyl or a heteroaryl of 5
or 6 ring members, wherein a carbon adjacent to the carbon at the
point of attachment of said phenyl or heteroaryl ring to A is
optionally substituted by R.sup.32, the other carbon adjacent to
the carbon at the point of attachment is optionally substituted by
R.sup.36, a carbon adjacent to R.sup.32 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.33, a carbon adjacent to R.sup.35 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.35, and any carbon adjacent to both R.sup.33 and R.sup.35 is
optionally substituted by R.sup.34; R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36 are independently selected from the group
consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino,
alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,
hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, and
Q.sup.b; A is a bond or (CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr
wherein rr is 0 or 1, pa is an integer selected from 0 through 3,
and W.sup.7 is N(R.sup.7); R.sup.7 is hydrido or alkyl; R.sup.15is
selected from the group consisting of hydrido, halo, alkyl, and
haloalkyl; X.sup.o is selected from the group consisting of
hydrido, hydroxy, hydroxyamino, amidino, amino, cyano,
hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio,
alkoxyamino, haloalkyl, haloalkoxy, and halo; R.sup.2 is Z.sup.0-Q;
Z.sup.0 is a bond; Q is phenyl or a heteroaryl of 5 or 6 ring
members, wherein a carbon adjacent to the carbon at the point of
attachment of said phenyl or heteroaryl ring to Z.sup.0 is
optionally substituted by R.sup.9, the other carbon adjacent to the
carbon at the point of attachment is optionally substituted by
R.sup.13, a carbon adjacent to R.sup.9 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.10, a carbon adjacent to R.sup.13 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.12, and any carbon adjacent to both R.sup.10 and R.sup.12 is
optionally substituted by R.sup.11; R.sup.9, R.sup.11, and R.sup.13
are independently selected from the group consisting of hydrido,
hydroxy, amino, amidino, guanidino, alkylamino, alkylthio, alkoxy,
alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkyl, halo,
haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and
cyano; R.sup.10 and R.sup.12 are independently selected from the
group consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkyl, alkoxy, alkoxyamino, hydroxy, amino, alkylamino,
alkylsulfonamido, amidosulfonyl, hydroxyalkyl, aminoalkyl, halo,
haloalkyl, carboalkoxy, carboxy, carboxamido, carboxyalkyl, and
cyano; Y.sup.0 is phenyl or a heteroaryl of 5 or 6 ring members,
wherein one carbon of said phenyl or said heteroaryl is substituted
by Q.sup.s, a carbon two or three atoms from the point of
attachment of Q.sup.s to said phenyl or said heteroaryl is
substituted by Q.sup.b, a carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.17,
another carbon adjacent to the point of attachment of Q.sup.s is
optionally substituted by R.sup.18, a carbon adjacent to Q.sup.b is
optionally substituted by R.sup.16, and another carbon adjacent to
Q.sup.b is optionally substituted by R.sup.19; R.sup.16, R.sup.17,
R.sup.18, and R.sup.19 are independently selected from the group
consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,
alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl,
alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl,
haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano; R.sup.16 or
R.sup.19 is optionally NR.sup.20R.sup.21 or
C(NR.sup.25)NR.sup.23R.sup.24- , with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido; Q.sup.b is
selected from the group consisting of NR.sup.20R.sup.21, hydrido,
and C(NR.sup.25)NR.sup.23R.sup.24; R.sup.20, R.sup.21, R.sup.23,
R.sup.24, and R.sup.25 are independently hydrido or alkyl; Q is
CH.sub.2.
33. Compound of claim 32 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl,
3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl,
2-thiazolyl, 3-isoxazolyl, and 5-isoxazolyl, wherein a carbon
adjacent to the carbon at the point of attachment of said phenyl or
heteroaryl ring to A is optionally substituted by R.sup.32, the
other carbon adjacent to the carbon at the point of attachment is
optionally substituted by R.sup.36, a carbon adjacent to R.sup.32
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.33, a carbon adjacent to R.sup.36
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.35, and any carbon adjacent to both
R.sup.33 and R.sup.35 is optionally substituted by R.sup.34;
R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino,
N-methylamino, dimethylamino, methoxyamino, methylthio, ethylthio,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro,
chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl,
amidocarbonyl, carboxy, cyano, and Q.sup.b; A is selected from the
group consisting of a bond, NH, N(CH.sub.3), CH.sub.2, CH.sub.3CH,
and CH.sub.2CH.sub.2; X.sup.o is selected from the group consisting
of hydrido, hydroxy, amino, amidino, aminomethyl, cyano, methyl,
trifluoromethyl, hydroxymethyl, chloro, and fluoro; R.sup.2 is
selected from the group consisting of phenyl, 2-thienyl, 2-furyl,
2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl, and
3-pyridyl, wherein a carbon adjacent to the carbon at the point of
attachment of said phenyl or heteroaryl ring to the 1,4-quinone
ring is optionally substituted by R.sup.9, the other carbon
adjacent to the carbon at the point of attachment is optionally
substituted by R.sup.13, a carbon adjacent to R.sup.9 and two atoms
from the carbon at the point of attachment is optionally
substituted by R.sup.10, a carbon adjacent to R.sup.13 and two
atoms from the carbon at the point of attachment is optionally
substituted by R.sup.12, and any carbon adjacent to both R.sup.10
and R.sup.12 is optionally substituted by R.sup.11; R.sup.9,
R.sup.11, and R.sup.13 are independently selected from the group
consisting of hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy,
amino, N-methylamino, N,N-dimethylamino, methylthio,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro,
chloro, bromo, amidosulfonyl, N-methylamidosulfonyl,
N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,
amidocarbonyl, N-methylamidocarbonyl, carboxy, and cyano; R.sup.10
and R.sup.12 are independently selected from the group consisting
of hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl,
N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarb- onyl,
N-(3-fluorobenzyl)amidocarbonyl,
N-(2-trifluoromethylbenzyl)amidocar- bonyl,
N-(1-phenylethyl)amidocarbonyl,
N-(1-methyl-1-phenylethyl)amidocarb- onyl, N-benzylamidosulfonyl,
N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl,
N-isopropylamidocarbonyl, N-propylamidocarbonyl,
N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,
N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl,
N-cyclohexylamidocarbonyl, guanidino, methyl, ethyl, methoxy,
ethoxy, hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
carboxy, carboxymethyl, amino, acetamido, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido,
aminomethyl, N-methylamino, dimethylamino, methoxyamino,
amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,
methanesulfonamido, methoxycarbonyl, fluoro, chloro, bromo, and
cyano; Y.sup.0 is selected from the group consisting of:
1-Q.sup.b-4-Q.sup.s-2-R.sup.16-3-R.sup.17-5-R.sup.18-6-R.sup.19
benzene, 2-Q.sup.b-5-Q.sup.s-6-R.sup.17-4R.sup.18-3-R.sup.19
pyridine, 2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 thiophene,
3-Q.sup.b-6-Q.sup.s-2-R.sup.16-5-R.sup.18-4-R.sup.19 pyridine,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 thiophene,
3-Q.sup.b-5-Q.sup.s-4R.sup.16-2-R.sup.19 furan,
2-Q.sup.b-5-Q.sup.s-3-R.s- up.16-4-R.sup.17 furan,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 pyrrole,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 pyrrole,
4-Q.sup.b-2-Q.sup.s-5-R.sup.19 thiazole, and
2-Q.sup.b-5-Q.sup.s-4-R.sup.- 17 thiazole; R.sup.16, R.sup.17,
R.sup.18, and R.sup.19 are independently selected from the group
consisting of hydrido, methyl, ethyl, amidino, guanidino, methoxy,
hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl,
N-methylamino, dimethylamino, methylthio, ethylthio,
trifluoromethylthio, methylsulfinyl, methylsulfonyl,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,
trifluoromethoxy, fluoro, chloro, hydroxymethyl, carboxy, and
cyano; Q.sup.b is NR.sup.20R.sup.21 or
C(NR.sup.25)NR.sup.23R.sup.24; R.sup.20, R.sup.21, R.sup.23,
R.sup.24, and R.sup.25 are independently selected from the group
consisting of hydrido, methyl, and ethyl; Q.sup.s is CH.sub.2.
34. Compound of claim 33 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
2-aminophenyl, 3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl,
3-carboxyphenyl, 3-carboxy-5-hydroxyphenyl, 3-chlorophenyl,
4-chlorophenyl, 3,4dichlorophenyl, 2-fluorophenyl, 3-fluorophenyl,
3,4-difluorophenyl, 3-hydroxyphenyl, 4hydroxyphenyl,
3-methoxyaminophenyl, 3-methoxyphenyl, 4-methoxyphenyl,
3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoromethylphenyl,
2-imidazoyl, 2-pyridyl, 3-pyridyl,
5-chloro-3-trifluoromethyl-2-pyridyl, 4-pyridyl, 2-thienyl,
3-thienyl, and 3-trifluoromethyl-2-pyridyl; A is CH.sub.2 or
CH.sub.2CH.sub.2; X.sup.o is selected from the group consisting of
hydrido, hydroxy, amino, amidino, aminomethyl, cyano, methyl,
trifluoromethyl, hydroxymethyl, and fluoro; R.sup.2 is selected
from the group consisting of 3-amidocarbonyl-5-aminophenyl,
3-amidocarbonyl-5-aminophenyl,
3-amino-5-(N-benzylamidocarbonyl)phenyl,
3-amino-5-(N-(2-chlorobenzyl)ami- docarbonyl )phenyl,
3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,
3-amino-54N-(1-methyl-1- -phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-benzylamidosulfonyl)phenyl- ,
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl,
3-amino-5-(N-ethylamidocarbonyl)phenyl,
3-amino-5-(N-isopropylamidocarbon- yl)phenyl,
3-amino-5-(N-propylamidocarbonyl)phenyl,
3-amino-5-(N-isobutylamidocarbonyl)phenyl,
3-amino-5-(N-(2-butyl)amidocar- bonyl)phenyl,
3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,
3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,
3-amino-5-(N-cyclohexylamid- ocarbonyl)phenyl,
5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl,
5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl,
3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl,
3-carboxyphenyl, 3-carboxy-5-aminophenyl,
3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl,
3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl,
3-chlorophenyl, 2-chlorophenyl, 3-cyanophenyl, 3,5-diaminophenyl,
3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,
2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,
3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,
3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,
3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl,
4-methylphenyl, phenyl, 3-trifluoroacetamidophenyl,
3-trifluoromethylphenyl, 2-trifluoromethylphenyl,
5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl,
4-pyridyl, 2-thienyl, and 3-thienyl; Y.sup.0 is selected from the
group consisting of: 1-Q.sup.b-4-Q.sup.s-2-R-
.sup.16-3-R.sup.17-5-R.sup.18-6-R.sup.19 benzene,
2-Q.sup.b-5-Q.sup.s-6-R.- sup.17-4-R.sup.18-3-R.sup.19 pyridine,
3-Q.sup.b-6-Q.sup.s-2-R.sup.16-5-R.- sup.18-4-R.sup.19 pyridine,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 thiophene, and
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 thiophene; R.sup.16 and
R.sup.18 are independently selected from the group consisting of
hydrido, amidino, amino, aminomethyl, methoxy, methylamino,
hydroxy, hydroxymethyl, fluoro, chloro, and cyano; R.sup.17 and
R.sup.18 are independently selected from the group consisting of
hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy,
and cyano; Q.sup.b is C(NR.sup.25)NR.sup.23R.sup.24; R.sup.23,
R.sup.24, and R.sup.25 are independently hydrido or methyl; Q.sup.s
is CH.sub.2.
35. Compound of claim 34 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl, 3-chlorophenyl,
4-chlorophenyl, 3,4-dichlorophenyl, 2-fluorophenyl, 4-methylphenyl,
phenyl, 2-imidazoyl, 3-pyridyl, 4-pyridyl, and
3-trifluoromethyl-2-pyridyl; A is CH.sub.2 or CH.sub.2CH.sub.2;
X.sup.o is selected from the group consisting of hydrido, hydroxy,
amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl,
hydroxymethyl, and fluoro; R.sup.2 is selected from the group
consisting of 3-amidocarbonyl-5-aminophenyl,
3-amino-5-(N-benzylamidocarbonyl)phenyl,
3-amino-5-(N-(2-chlorobenzyl)ami- docarbonyl)phenyl,
3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-methyl-- 1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-benzylamidosulfonyl)pheny- l,
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl,
3-amino-5-(N-ethylamidocarbonyl)phenyl,
3-amino-5-(N-isopropylamidocarbon- yl)phenyl,
3-amino-5-(N-propylamidocarbonyl)phenyl,
3-amino-5-(N-isobutylamidocarbonyl)phenyl,
3-amino-5-(N-(2-butyl)amidocar- bonyl)phenyl,
3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,
3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,
3-amino-5-(N-cyclohexylamid- ocarbonyl)phenyl, 3-aminophenyl,
3-carboxy-5-aminophenyl, 3-chlorophenyl, 3,5-diaminophenyl,
3-dimethylaminophenyl, 3-hydroxyphenyl,
3-methanesulfonylaminophenyl, 3-methylaminophenyl, 2-methylphenyl,
3-methylphenyl, phenyl, 3-trifluoroacetamidophenyl,
3-bromo-2-thienyl, 2-thienyl, and 3-thienyl; Y.sup.0 is selected
from the group consisting of 5amidino-2-thienylmethyl,
4-amidinobenzyl, 2-fluoro-4-amidinobenzyl, and
3-fluoro-4amidinobenzyl.
36. Compound of claim 29 where said compound is selected from the
group of the Formula: 108or a pharmaceutically acceptable salt
thereof, wherein B, A, R.sup.2, X.sup.o, and Y.sup.0 are selected
to form a compound selected from the group consisting of; R.sup.2
is 3-aminophenyl, B is phenyl, A is CH.sub.2, Y.sup.0 is
4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is 3-aminophenyl, B
is 3-chlorophenyl, A is CH.sub.2CH.sub.2, Y.sup.0 is 4-
amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is3-aminophenyl, B is
phenyl, A is CH.sub.2, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
hydrido; R.sup.2 is 3-aminophenyl, B is 2-imidazoyl, A is
CH.sub.2CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl, and X.sup.0
is chloro; R.sup.2 is 3-amidocarbonyl-5-aminophenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is chloro; R.sup.2 is
3-amino-5-(N-benzylamidocarbonyl)phenyl, B is 3-chlorophenyl, A is
CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro; R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is chloro; R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)- phenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is chloro; R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is chloro; R.sup.2 is 3,5-diaminophenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is chloro; R.sup.2 is 3-amino-5-carboxyphenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is chloro; R.sup.2 is 3-amidocarbonyl-5-aminophenyl, B
is 3-chlorophenyl, A is CH.sub.2CH.sub.2, Y.sup.0 is
4-amidinobenzyl, and X.sup.0 is hydrido; R.sup.2 is
3-amino-5-(N-benzylamidocarbonyl)phenyl, B is 3-chlorophenyl, A is
CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
hydrido; R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is hydrido; R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl- )phenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is hydrido; R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is hydrido; R.sup.2 is 3,5-diaminophenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is hydrido; and R.sup.2 is 3-amino-5-carboxyphenyl, B
is 3-chlorophenyl, A is CH.sub.2CH.sub.2, Y.sup.0 is
4-amidinobenzyl, and X.sup.0 is hydrido.
37. Compound of claim 22 of the Formula: 109or a pharmaceutically
acceptable salt thereof, wherein; B is selected from the group
consisting of hydrido, C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl,
and C2-C8 haloalkyl, wherein each member of group B is optionally
substituted at any carbon up to and including 6 atoms from the
point of attachment of B to A with one or more of the group
consisting of R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36;
R.sup.32, R.sup.33, R.sup.34, R.sup.34, and R.sup.36 are
independently selected from the group consisting of hydrido,
acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy,
amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl,
halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl,
carboalkoxy, carboxy, carboxamido, cyano, and Q.sup.b; A is a bond
or (CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr wherein rr is 0 or 1, pa
is an integer selected from 0 through 3, and W.sup.7 is
(R.sup.7)NC(O) or N(R.sup.7); R.sup.7 is selected from the group
consisting of hydrido, hydroxy and alkyl; R.sup.15 is selected from
the group consisting of hydrido, halo, alkyl, and haloalkyl;
X.sup.o is selected from the group consisting of hydrido, hydroxy,
hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl,
alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl,
haloalkoxy, and halo; R.sup.2 is Z.sup.0-Q; Z.sup.0 is selected
from the group consisting of a bond, CH.sub.2, CH.sub.2CH.sub.2,
W.sup.0--(CH(R.sup.42)).sub.p wherein p is 0 or 1 and W.sup.0 is
selected from the group consisting of O, S, and N(R.sup.41);
R.sup.41 and R.sup.42 are independently hydrido or alkyl; Q is
phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon
adjacent to the carbon at the point of attachment of said phenyl or
heteroaryl ring to Z.sup.0 is optionally substituted by R.sup.9,
the other carbon adjacent to the carbon at the point of
attachment-is optionally substituted by R.sup.13, a carbon adjacent
to R.sup.9 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.10, a carbon adjacent to
R.sup.13 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.12, and any carbon adjacent to
both R.sup.10 and R.sup.12 is optionally substituted by R.sup.11;
R.sup.9, R.sup.11, and R.sup.13 are independently selected from the
group consisting of hydrido, hydroxy, amino, amidino, guanidino,
alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl,
alkylsulfonyl, amidosulfonyl, alkyl, alkoxy, halo, haloalkyl,
haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboxy, carboxamido,
and cyano; R.sup.10 and R.sup.12 are independently selected from
the group consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl,
heteroaryl, heterocyclyl, alkoxy, cycloalkoxy, cycloalkylalkoxy,
aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy,heterocyclyloxy,
heterocyclylalkoxy, hydroxy, amino, alkoxyamino, alkylamino,
arylamino, aralkylamino, heteroarylamino, heteroaralkylamino,
heterocyclylamino, heterocyclylalkylamino, alkylsulfonamido,
amidosulfonyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl,
heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl,
cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl,
hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl,
carboxamido, halo, haloalkyl, and cyano; Y.sup.0 is phenyl or a
heteroaryl of 5 or 6 ring members, wherein one carbon of said
phenyl or said heteroaryl is substituted by Q.sup.s, a carbon two
or three atoms from the point of attachment of Q.sup.s to said
phenyl or said heteroaryl is substituted by Q.sup.b, a carbon
adjacent to the point of attachment of Q.sup.s is optionally
substituted by R.sup.17, another carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.18, a
carbon adjacent to Q.sup.b is optionally substituted by R.sup.16,
and another carbon adjacent to Q.sup.b is optionally substituted by
R.sup.19; R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are
independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl,
haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,
aminoalkyl, and cyano; R.sup.16 or R.sup.19 is optionally selected
from the group consisting of NR.sup.20R.sup.21,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24), and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido; Q.sup.b is
selected from the group consisting of NR.sup.20R.sup.21, hydrido,
C(NR.sup.25)NR.sup.23R.su- p.24, and
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24), with the proviso that
no more than one of R.sup.20 and R.sup.21 is hydroxy at the same
time and with the further proviso that no more than one of R.sup.23
and R.sup.24 is hydroxy at the same time; R.sup.20, R.sup.21,
R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, alkyl, and hydroxy;
Q.sup.s is selected from the group consisting of a bond, CH.sub.2,
and CH.sub.2CH.sub.2.
38. Compound of claim 37 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
hydrido, ethyl, 2-propynyl, 2-propenyl, propyl, isopropyl, butyl,
2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl,
2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl,
2-pentynyl, 3-pentynyl, 2-pentyl, 1-methyl-2-butenyl,
1-methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl,
1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl,
2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl,
3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl,
3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4hexynyl,
2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl,
1-methylpentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl,
3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl,
1-ethyl-2-butynyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl,
5-heptenyl, 6-heptenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl,
5-heptenyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl,
1-methyl-4-hexenyl, 1-methyl-5-hexenyl, 1-methyl-2-hexynyl,
1-methyl-3-hexynyl, 1-methyl-4-hexynyl, 3-heptyl,
1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl,
1-butyl-2-propenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl,
2,2,2-trifluoroethyl, 2,2-difluoropropyl,
4-trifluoromethyl-5,5,5,-triflu- oropentyl,
4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and
3,3,3-trifluoropropyl, wherein each member of group B is optionally
substituted at any carbon up to and including 5 atoms from the
point of attachment of B to A with one or more of the group
consisting of R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36;
R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy,
hydroxy, amino, methoxyamino, ethoxyamino, acetamido,
trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino,
methylthio, ethylthio, isopropylthio, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,
N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxye- thyl,
methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and
Q.sup.b; A is selected from the group consisting of bond, NH,
N(CH.sub.3), N(OH), CH.sub.2, CH.sub.3CH, CF.sub.3CH, NHC(O),
N(CH.sub.3)C(O), C(O)NH, C(O)N(CH.sub.3), CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2, CH.sub.3CHCH.sub.2, and
CF.sub.3CHCH.sub.2; X.sup.o is selected from the group consisting
of hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl,
1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino,
methylthio, ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy,
fluoro, chloro, and bromo; R.sup.2 is Z.sup.0-Q; Z.sup.0 is
selected from the group consisting of a bond, CH.sub.2,
CH.sub.2CH.sub.2, O, S, NH, N(CH.sub.3), OCH.sub.2, SCH.sub.2,
N(H)CH.sub.2, and N(CH.sub.3)CH.sub.2; Q is selected from the group
consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl,
2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl,
4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, S-isoxazolyl, 2-pyridyl,
3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl,
5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and
1,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at the
point of attachment of said phenyl or heteroaryl ring to Z.sup.0 is
optionally substituted by R.sup.9, the other carbon adjacent to the
carbon at the point of attachment is optionally substituted by
R.sup.13, a carbon adjacent to R.sup.9 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.10, a carbon adjacent to R.sup.13 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.12, and any carbon adjacent to both R.sup.10 and R.sup.12 is
optionally substituted by R.sup.11; R.sup.9, R.sup.11, and R.sup.13
are independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl,
methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,
N-methylamino, N,N-dimethylamino, N-ethylamino, methylthio,
ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl,
N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,
2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;
R.sup.10 and R.sup.12 are independently selected from the group
consisting of hydrido, amidino, guanidino, carboxy, carboxymethyl,
methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy,
propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido,
trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,
N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,
amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,
amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl,
N-benzylamidocarbonyl, N-(2-chlorobenzyl )amidocarbonyl,
N-(3-fluorobenzyl)amidocarbonyl,
N-(2-trifluoromethylbenzyl)amidocarbonyl- ,
N-(1-phenylethyl)amidocarbonyl,
N-(1-methyl-1-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl,
N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl,
N-isopropylamidocarbonyl, N-propylamidocarbonyl,
N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,
N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl,
N-cyclohexylamidocarbonyl, fluoro, chloro, bromo, cyano,
cyclobutoxy, cyclohexoxy, cyclohexylmethoxy,
4-trifluoromethycyclohexylmethoxy, cyclopentoxy, benzyl, benzyloxy,
4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy,
4-bromobenzylamino, 5-bromopyrid-2-ylmethylamino,
4-butoxyphenamino, 3-chlorobenzyl, 4-chlorophenoxy,
4-chloro-3-ethylphenoxy, 4-chloro-3-ethylbenzylamino,
4-chloro-3-ethylphenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy,
4-chlorobenzylsulfonyl, 4-chlorophenylamino,
4-chlorophenylsulfonyl, 5-chloropyrid-3-yloxy,
2-cyanopyrid-3-yloxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy,
3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorophenoxy,
3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy,
2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy,
3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyloxy,
3,5-dimethylbenzyloxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy,
3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy,
4-fluorobenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy,
3-fluoro-5-trifluoromethylbenzyloxy,
4-fluoro-2-trifluoromethylbenzyloxy,
4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy,
4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy,
2-fluorobenzyloxy, 4-fluorophenylamino,
2-fluorotrifluoromethylphenoxy, 4-isopropylbenzyloxy,
3-isopropylphenoxy, 4-isopropylphenoxy, 4-isopropyl -3-methyl
phenoxy, 4-isopropyl benzyloxy, 3-isopropylphenoxy,
4-isopropylphenoxy, 4-isopropyl-3-methylphenoxy, phenylamino,
1-phenylethoxy, 2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino,
phenylsulfonyl, 3-trifluoromethoxybenzyloxy,
4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy,
4-trifluoromethoxyphenoxy, 3-trifluoromethylbenzyloxy,
4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy,
3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy,
4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy,
3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy,
2,3,4-trifluorophenoxy, 2,3,5-trifluorophenoxy,
3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy,
and 3-trifluoromethylthiophenoxy; Y.sup.0 is selected from the
group consisting of: 1-Q.sup.b-4-Q.sup.s-2-R-
.sup.16-5-R.sup.18-6-R.sup.19 benzene,
2-Q.sup.b-5-Q.sup.s-6-R.sup.17-5R.s- up.18-3-R.sup.19 pyridine,
3-Q.sup.b-6-Q.sup.s-2-R.sup.16-5-R.sup.18-4-R.s- up.19 pyridine,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-6-R.sup.18 pyrazine,
3-Q.sup.b-6-Q.sup.s-2-R.sup.18-5-R.sup.18-4-R.sup.19 pyridazine,
2-Q.sup.b-5-Q.sup.s-4-R.sup.17-6-R.sup.18 pyrimidine,
5-Q.sup.b-2-Q.sup.s-4-R.sup.16-6-R.sup.19 pyrimidine,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 thiophene,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 thiophene,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 furan,
2Q.sup.b-5-Q.sup.s-3-R.s- up.16-4-R.sup.17 furan,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 pyrrole ,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 pyrrole,
4-Q.sup.b-2-Q.sup.s-5-R.sup.19 imidazole,
2-Q.sup.b-4-Q.sup.s-5-R.sup.17 imidazole,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16 isoxazole,
5-Q.sup.b-3-Q.sup.s-4-R.sup.16 isoxazole,
2-Q.sup.b-5-Q.sup.s-4-R.sup.16 pyrazole,
4-Q.sup.b-2-Q.sup.s-5-R.sup.19 thiazole, and
2-Q.sup.b-5-Q.sup.s-4-R.sup.17 thiazole; R.sup.16, R.sup.17,
R.sup.18, and R.sup.19 are independently selected from the group
consisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy,
amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy,
amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,
dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,
trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,
ethylsulfonyl, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, and cyano; R .sup.16
or R.sup.19 is optionally selected from the group consisting of
NR.sup.20R.sup.21, C(NR.sup.25)NR.sup.23R.sup.24, and
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24), with the proviso that
R.sup.16, R.sup.19, and Q.sup.b are not simultaneously hydrido;
Q.sup.b is selected from the group consisting of NR.sup.20R.sup.21,
hydrido, C(NR.sup.25)NR.sup.23R.sup.24, and
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.s- up.24), with the proviso
that no more than one of R.sup.20 and R.sup.21 is hydroxy at the
same time and with the further proviso that no more than one of
R.sup.23 and R.sup.24 is hydroxy at the same time; R.sup.20,
R.sup.21, R.sup.23, R.sup.24, R.sup.25, and R.sup.26are
independently selected from the group consisting of hydrido,
methyl, ethyl, propyl, butyl, isopropyl, and hydroxy; Q.sup.s is
selected from the group consisting of a bond, CH.sub.2, and
CH.sub.2CH.sub.2.
39. Compound of claim 38 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl,
2-butyl, (R)-2-butyl, (S)-2-butyl, tert-butyl, isobutyl, 1-pentyl,
3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl,
6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl,
1-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl,
3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl,
6-hydroxyhexyl, 2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl,
3-guanidinopropyl, 4guanidinobutyl, 3-hydroxypropyl, 4hydroxybutyl,
6cyanohexyl, 2-dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl,
(S)-2-methylbutyl, 3-aminopropyl, 2-hexyl, and 4aminobutyl; A is
selected from the group consisting of a bond, CH.sub.2, NHC(O),
CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2, and CH.sub.3CHCH.sub.2;
X.sup.o is selected from the group consisting of hydrido, hydroxy,
amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano,
methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino,
methylthio, trifluoromethoxy, fluoro, and chloro; R.sup.2 is
Z.sup.0-Q; Z.sup.0 is selected from the group consisting of a bond,
CH.sub.2, O, S, NH, N(CH.sub.3), OCH.sub.2, and SCH.sub.2; Q is
selected from the group consisting of
3-amidocarbonyl-5-aminophenyl,
3-amino-5-(N-benzylamidocarbonyl)phenyl, 3-amino-5-benzylphenyl,
3-amino-5-(2-phenylethyl)phenyl, 3-amino-5-benzylaminophenyl,
3-amino-5-(2-phenylethylamino)phenyl, 3-amino-5-benzyloxyphenyl,
3-amino-5-(2-phenylethoxy)phenyl,
3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-methyl-- 1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-benzylamidosulfonyl)pheny- l,
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl,
3-amino-5-(N-ethylamidocarbonyl)phenyl,
3-amino-5-(N-isopropylamidocarbon- yl)phenyl,
3-amino-5-(N-propylamidocarbonyl)phenyl,
3-amino-5-(N-isobutylamidocarbonyl)phenyl,
3-amino-5-(N-(2-butyl)amidocar- bonyl)phenyl,
3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,
3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,
3-amino-5-(N-cyclohexylamid- ocarbonyl)phenyl,
5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl,
5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl,
3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl,
3-amino-5-(4-trifluoromethylbe- nzylamino)phenyl,
3-amino-5-(4-trifluoromethylbenzyloxy)phenyl, 3-carboxyphenyl,
3-carboxy-5-hydroxyphenyl, 3-amino-5-carboxyphenyl, 3-chlorophenyl,
2-chlorophenyl, 3-cyanophenyl, 3,5-diaminophenyl,
3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,
2-hydroxyphenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl,
2-methoxyphenyl, 3-methoxyphenyl, 3-methoxyaminophenyl,
3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl,
2-methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl,
3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl,
2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl,
3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl;
Y.sup.0 is selected from the group consisting of:
1-Q.sup.b-4-Q.sup.s-2-R.sup.16-3-R.sup.17-5-R.sup.18-6-R.sup.19
benzene, 2-Q.sup.b-5-Q.sup.s-6-R.sup.17-4-R.sup.18-3-R.sup.19
pyridine, 3-Q.sup.b-6-Q.sup.s-2-R.sup.16-5-R.sup.18-4-R.sup.19
pyridine, 3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 thiophene, and
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 thiophene; R.sup.16 and
R.sup.19 are independently selected from the group consisting of
hydrido, amidino, amino, aminomethyl, methoxy, methylamino,
hydroxy, hydroxymethyl, fluoro, chloro, and cyano; R.sup.16 or
R.sup.19 is optionally C(NR.sup.25)NR.sup.23R.sup.24with the
proviso that R.sup.16, R.sup.19, and Q.sup.b are not simultaneously
hydrido; R.sup.17 and R.sup.18 are independently selected from the
group consisting of hydrido, fluoro, chloro, hydroxy,
hydroxymethyl, amino, carboxy, and cyano; Q.sup.b is
C(NR.sup.25)NR.sup.23R.sup.24 or hydrido; R.sup.23, R.sup.24, and
R.sup.25 are independently hydrido or methyl; Q.sup.s is
CH.sub.2.
40. Compound of claim 37 of the Formula: 110or a pharmaceutically
acceptable salt thereof, wherein; B is selected from the group
consisting of hydrido, C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl,
and C2-C8 haloalkyl, wherein each member of group B is optionally
substituted at any carbon up to and including 6 atoms from the
point of attachment of B to A with one or more of the group
consisting of R.sup.32, R.sup.33, R.sup.34, R.sup.35, R.sup.36;
R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy,
amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl,
halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy,
carboxamido, cyano, and Q.sup.b; A is a bond or
(CH(R.sup.15)).sub.pa--(W.sup.7).sub.r- r wherein rr is 0 or1, pa
is an integer selected from 0 through 3, and W.sup.7 is N(R.sup.7);
R.sup.7 is hydrido or alkyl; R.sup.15 is selected from the group
consisting of hydrido, halo, alkyl, and haloalkyl; X.sup.o is
selected from the group consisting of hydrido, hydroxy,
hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl,
alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl,
haloalkoxy, and halo; R.sup.2 is Z.sup.0-Q; Z.sup.0 is a bond; Q is
phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon
adjacent to the carbon at the point of attachment of said phenyl or
heteroaryl ring to Z.sup.0 is optionally substituted by R.sup.9,
the other carbon adjacent to the carbon at the point of attachment
is optionally substituted by R.sup.13, a carbon adjacent to R.sup.9
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.10, a carbon adjacent to R.sup.13
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.12, and any carbon adjacent to both
R.sup.10 and R.sup.12 is optionally substituted by R.sup.11;
R.sup.9, R.sup.11, and R.sup.13 are independently selected from the
group consisting of hydrido, hydroxy, amino, amidino, guanidino,
alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl,
amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,
carboxy, carboxamido, and cyano; R.sup.10 and R.sup.12 are
independently selected from the group consisting of hydrido,
acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy,
alkoxyamino, hydroxy, amino, alkylamino, alkylsulfonamido,
amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl,
carboalkoxy, carboxy, carboxamido, carboxyalkyl, and cyano; Y.sup.0
is phenyl or a heteroaryl of 5 or 6 ring members, wherein one
carbon of said phenyl or said heteroaryl is substituted by Q.sup.s,
a carbon two or three atoms from the point of attachment of Q.sup.s
to said phenyl or said heteroaryl is substituted by Q.sup.b, a
carbon adjacent to the point of attachment of Q.sup.s is optionally
substituted by R.sup.17, another carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.18, a
carbon adjacent to Q.sup.b is optionally substituted by R.sup.16,
and another carbon adjacent to Q.sup.b is optionally substituted by
R.sup.19; R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are
independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl,
haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,
aminoalkyl, and cyano; R.sup.16 or R.sup.19 is optionally selected
from the group consisting of NR.sup.20R.sup.21,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24), and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido; Q.sup.b is
selected from the group consisting of NR.sup.20R.sup.21, hydrido,
N(R.sup.26)C(NR.sup.25)N(- R.sup.23)(R.sup.24), and
C(NR.sup.25)NR.sup.23R.sup.24; R.sup.20, R.sup.21, R.sup.23,
R.sup.24, R.sup.25, and R.sup.26 are independently hydrido or
alkyl; Q.sup.s is CH.sub.2.
41. Compound of claim 40 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl,
butyl,2-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl,
2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 2-pentynyl,
3-pentynyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 2-methyl-2-butenyl,
3-methylbutyl, 3-methyl-2-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl,
4hexenyl, 2-hexynyl, 3-hexynyl, 4hexynyl, 2-hexyl,
1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-2-pentynyl,
1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1-heptyl,
2-heptenyl, 3-heptenyl, 4heptenyl, 5-heptenyl, 2-heptenyl,
3-heptenyl, 4-heptenyl, 5-heptenyl, 2-heptyl, 1-methyl-2-hexenyl,
1-methyl-3-hexenyl, 1-methylhexenyl, 1-methyl-2-hexynyl,
1-methyl-3-hexynyl, 1-methyl-4hexynyl, 3-heptyl,
1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-2-pentynyl,
1-ethyl-3-pentynyl, 2,2,2-trifluoroethyl, 2,2-difluoropropyl,
4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl,
5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein each
member of group B is optionally substituted at any carbon up to and
including 5 atoms from the point of attachment of B to A with one
or more of the group consisting of R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36; R.sup.32, R.sup.33, R.sup.34, R.sup.35, and
R.sup.36 are independently selected from the group consisting of
hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy,
hydroxy, amino, N-methylamino, dimethylamino, methoxyamino,
methylthio, ethylthio, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,
N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, carboxy,
cyano, and Q.sup.b; A is selected from the group consisting of a
bond, NH, N(CH.sub.3), CH.sub.2, CH.sub.3CH, and CH.sub.2CH.sub.2;
A is optionally selected from the group consisting of
CH.sub.2N(CH.sub.3), CH.sub.2N(CH.sub.2CH.sub.3),
CH.sub.2CH.sub.2N(CH.sub.3), and
CH.sub.2CH.sub.2N(CH.sub.2CH.sub.3) with the proviso that B is
hydrido; X.sup.o is selected from the group consisting of hydrido,
hydroxy, amino, amidino, aminomethyl, cyano, methyl,
trifluoromethyl, hydroxymethyl, chloro, and fluoro; R.sup.2 is
selected from the group consisting of phenyl, 2-thienyl, 2-furyl,
2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl, and
3-pyridyl, wherein a carbon adjacent to the carbon at the point of
attachment of said phenyl or heteroaryl ring to the 1,4-quinone
ring is optionally substituted by R.sup.9, the other carbon
adjacent to the carbon at the point of attachment is optionally
substituted by R.sup.13, a carbon adjacent to R.sup.9 and two atoms
from the carbon at the point of attachment is optionally
substituted by R.sup.10, a carbon adjacent to R.sup.13 and two
atoms from the carbon at the point of attachment is optionally
substituted by R.sup.12, and any carbon adjacent to both R.sup.10
and R.sup.12 is optionally substituted by R.sup.11; R.sup.9,
R.sup.11, and R.sup.13 are independently selected from the group
consisting of hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy,
amino, N-methylamino, N,N-dimethylamino, methylthio,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro,
chloro, bromo, amidosulfonyl, N-methylamidosulfonyl,
N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,
amidocarbonyl, N-methylamidocarbonyl, carboxy, and cyano; R.sup.10
and R.sup.12 are independently selected from the group consisting
of hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl,
N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarb- onyl,
N-(3-fluorobenzyl)amidocarbonyl,
N-(2-trifluoromethylbenzyl)amidocar- bonyl,
N-(1-phenylethyl)amidocarbonyl,
N-(1-methyl-1-phenylethyl)amidocarb- onyl, N-benzylamidosulfonyl,
N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl,
N-isopropylamidocarbonyl, N-propylamidocarbonyl,
N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,
N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl,
N-cyclohexylamidocarbonyl, guanidino, methyl, ethyl, methoxy,
ethoxy, hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
carboxy, carboxymethyl, amino, acetamido, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido,
aminomethyl, N-methylamino, dimethylamino, methoxyamino,
amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,
methanesulfonamido, methoxycarbonyl, fluoro, chloro, bromo, and
cyano; Y.sup.0 is selected from the group consisting of:
1-Q.sup.b-4-Q.sup.s-2-R.sup.17-3-R.sup.17-5-R.sup.18-6-R.sup.19
benzene, 2-Q.sup.b-5-Q.sup.s-6-R.sup.17-4-R.sup.18-3-R.sup.19
pyridine, 2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 thiophene,
3-Q.sup.b-6-Q.sup.s-2-R.sup.16-5-R.sup.18-4R.sup.19 pyridine,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 thiophene,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 furan,
2-Q.sup.b-5-Q.sup.s-3-R.- sup.16-4-R.sup.17 furan,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 pyrrole,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 pyrrole,
4-Q.sup.b-2-Q.sup.s-5-R.sup.19 thiazole, and
2-Q.sup.b-5-Q.sup.s-4-R.sup.- 17 thiazole; R.sup.16, R.sup.17,
R.sup.18, and R.sup.19 are independently selected from the group
consisting of hydrido, methyl, ethyl, amidino, guanidino, methoxy,
hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl,
N-methylamino, dimethylamino, methylthio, ethylthio,
trifluoromethylthio, methylsulfinyl, methylsulfonyl,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,
trifluoromethoxy, fluoro, chloro, hydroxymethyl, carboxy, and
cyano; Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, C(NR.sup.25)NR.sup.23R.sup.24, and
N(R.sup.26)C(NR.sup.25)N(R.sup.23 )(R.sup.24); R.sup.20, R.sup.21,
R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, methyl, and ethyl;
Q.sup.s is CH.sub.2.
42. Compound of claim 41 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl,
2-butyl, (R)-2-butyl, (S)-2-butyl, tert-butyl, isobutyl, 1-pentyl,
3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl,
6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl,
1-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl,
3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl,
6-hydroxyhexyl, 2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl,
3-guanidinopropyl, 4guanidinobutyl, 3-hydroxypropyl, 4hydroxybutyl,
6-cyanohexyl, 2-dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl,
(S)-2-methylbutyl, 3-aminopropyl, 2-hexyl, and 4aminobutyl; A is
selected from the group consisting of a bond, CH.sub.2, CH.sub.3CH,
and CH.sub.2CH.sub.2; X.sup.o is selected from the group consisting
of hydrido, hydroxy, amino, amidino, aminomethyl, cyano, methyl,
trifluoromethyl, hydroxymethyl, and fluoro; R.sup.2 is selected
from the group consisting of 3-amidocarbonyl-5-aminophenyl,
3-amidocarbonyl-5-aminophenyl,
3-amino-5-(N-benzylamidocarbonyl)phenyl,
3-amino-5-(N-(2-chlorobenzyl )amidocarbonyl)phenyl,
3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-methyl-- 1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-benzylamidosulfonyl)pheny- l,
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl )phenyl,
3-amino-5-(N-ethylamidocarbonyl)phenyl,
3-amino-5-(N-isopropylamidocarbon- yl)phenyl,
3-amino-5-(N-propylamidocarbonyl)phenyl,
3-amino-5-(N-isobutylamidocarbonyl)phenyl,
3-amino-5-(N-(2-butyl)amidocar- bonyl)phenyl,
3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,
3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,
3-amino-5-(N-cyclohexylamid- ocarbonyl)phenyl,
5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl,
5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl,
3-amino-2-methylphenyl, 5amino-2-methylthiophenyl, 3-aminophenyl,
3-carboxyphenyl, 3-carboxy-5-aminophenyl,
3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl,
3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl,
3-chlorophenyl, 2-chlorophenyl, 3-cyanophenyl, 3,5-diaminophenyl,
3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,
2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,
3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,
3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,
3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl,
4-methylphenyl, phenyl, 3-trifluoroacetamidophenyl,
3-trifluoromethylphenyl, 2-trifluoromethylphenyl,
5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl,
4-pyridyl, 2-thienyl, and 3-thienyl; Y.sup.0 is selected from the
group consisting of: 1-Q.sup.b-4-Q.sup.s-2-R-
.sup.16-3-R.sup.17-5-R.sup.18-6-R.sup.19 benzene,
2-Q.sup.b-5-Q.sup.s-6-R.- sup.17-4-R.sup.18-3-R.sup.19 pyridine,
3-Q.sup.b-6-Q.sup.s-2-R.sup.16-5-R.- sup.18-4-R.sup.19 pyridine,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 thiophene, and
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 thiophene; R.sup.16 and
R.sup.19 are independently selected from the group consisting of
hydrido, amidino, amino, aminomethyl, methoxy, methylamino,
hydroxy, hydroxymethyl, fluoro, chloro, and cyano; R.sup.17 and
R.sup.18 are independently selected from the group consisting of
hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy,
and cyano; Q.sup.b is C(NR.sup.25)NR.sup.23R.sup.24; R.sup.23,
R.sup.24, and R.sup.25 are independently hydrido or methyl; Q.sup.s
is CH.sub.2.
43. Compound of claim 42 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl,
2-butyl, (R)-2-butyl, (S)-2-butyl, tert-butyl, isobutyl, 1-pentyl,
3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl,
6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl,
1-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl,
3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl,
6-hydroxyhexyl, 2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl,
3-guanidinopropyl, 4-guanidinobutyl, 3-hydroxypropyl,
4-hydroxybutyl, 6-cyanohexyl, 2-dimethylaminoethyl, 3-methylbutyl,
2-methylbutyl, (S)-2-methylbutyl, 3-aminopropyl, 2-hexyl, and
4-aminobutyl; A is selected from the group consisting of a bond,
CH.sub.2, CH.sub.3CH, and CH.sub.2CH.sub.2; X.sup.o is selected
from the group consisting of hydrido, hydroxy, amino, amidino,
aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, and
fluoro; R.sup.2 is selected from the group consisting of
3-amidocarbonyl-5-aminophenyl,
3-amino-5-(N-benzylamidocarbonyl)phenyl,
3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-methyl-- 1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-benzylamidosulfonyl)pheny- l,
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl,
3-amino-5-(N-ethylamidocarbonyl)phenyl,
3-amino-5-(N-isopropylamidocarbon- yl)phenyl,
3-amino-5-(N-propylamidocarbonyl)phenyl,
3-amino-5-(N-isobutylamidocarbonyl)phenyl,
3-amino-5-(N-(2-butyl)amidocar- bonyl)phenyl,
3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,
3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,
3-amino-5-(N-cyclohexylamid- ocarbonyl)phenyl, 3-aminophenyl,
3-carboxy-5-aminophenyl, 3-chlorophenyl, 3,5-diaminophenyl,
3-dimethylaminophenyl, 3-hydroxyphenyl,
3-methanesulfonylaminophenyl, 3-methylaminophenyl, 2-methylphenyl,
3-methylphenyl, phenyl, 3-trifluoroacetamidophenyl,
3-bromo-2-thienyl, 2-thienyl, and 3-thienyl; Y.sup.0 is selected
from the group consisting of 5-amidino-2-thienylmethyl,
4-amidinobenzyl, 2-fluoroamidinobenzyl, and
3-fluoroamidinobenzyl.
44. Compound of claim 37 where said compound is selected from the
group of the Formula: 111or a pharmaceutically acceptable salt
thereof, wherein B, A, R.sup.2, X.sup.o, and Y.sup.0 are selected
to form a compound selected from the group consisting of; R.sup.2
is 3-aminophenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y.sup.0
is 4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-aminophenyl, B is (S)-2-butyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
5-amino-2-fluorophenyl, B is isopropyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
2-methyl-3-aminophenyl, B is isopropyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X0 is chloro; R.sup.2 is 3-aminophenyl, B is
ethyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro; R.sup.2 is 3-aminophenyl, B is ethyl, A is a bond, Y.sup.0
is 4-amidino-2-fluorobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-aminophenyl, B is 2-propenyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X0 is chloro; R.sup.2 is 3-aminophenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidino-2-fluorobenzyl, and
X.sup.0 is chloro; R.sup.2 is 3-aminophenyl, B is isopropyl, A is a
bond, Y .sup.0is 4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-aminophenyl, B is 2-butyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is 3-aminophenyl, B
is (R)-2-butyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and
X.sup.0 is chloro; R.sup.2 is 3-aminophenyl, B is 2-propynyl, A is
a bond, Y .sup.0is 4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2
is 3-aminophenyl, B is 3-pentyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.0 is hydrido; R.sup.2 is 3-aminophenyl,
B is hydrido, A is CH.sub.2, Y.sup.0 is 4-amidinobenzyl, and
X.sup.0 is chloro; R.sup.2 is 3-aminophenyl, B is ethyl, A is
CH.sub.2, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
R.sup.2 is 3-aminophenyl, B is 2-methylpropyl, A is a bond, Y.sup.0
is 4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-aminophenyl, B is 2-propyl, A is CH.sub.3CH, Y.sup.0 is
4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is 3-aminophenyl, B
is propyl, A is a bond, Y.sup.0 is 4-amidino-2-fluorobenzyl, and
X.sup.o is chloro; R.sup.2 is 3-aminophenyl, B is
6-amidocarbonylhexyl, A is a bond, Y .sup.0is 4-amidinobenzyl, and
X.sup.0 is chloro; R.sup.2 is 3-aminophenyl, B is tert-butyl, A is
a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is hydrido; R.sup.2
is 3-aminophenyl, B is tert-butyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is 3-aminophenyl, B
is 3-hydroxypropyl, A is a bond, Y .sup.0is 4-amidinobenzyl, and
X.sup.0 is chloro; R.sup.2 is 3-aminophenyl, B is 2-methylpropyl, A
is a bond, Y.sup.0 is 4-amidino-2-fluorobenzyl, and X.sup.o is
chloro; R.sup.2 is 3-aminophenyl, B is butyl, A is a bond, Y.sup.0
is 4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-aminophenyl, B is 1-methoxy-2-propyl, A is a bond, Y .sup.0is
4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is 3-aminophenyl, B
is 2-methoxyethyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and
X.sup.0 is chloro; R.sup.2 is 3-aminophenyl, B is 2-propyl, A is a
bond, Y.sup.0 is 5-amidino-2-thienylmethyl, and X.sup.0 is chloro;
R.sup.2 is 5-amino-2-methylthiophenyl, B is 2-propyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-amino-5-carboxyphenyl, B is isopropyl, A is a bond, Y .sup.0 is
4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-amino-5-carbomethoxyphenyl, B is isopropyl, A is a bond, Y.sup.0
is 4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-aminophenyl, B is isopropyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.0 is bromo; R.sup.2 is
3-amino-5-carboxamidophenyl, B is isopropyl, A is a bond, Y.sup.0
is 4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-amino-5-(N-benzyl-N-methylamidocarbonyl)phenyl, B is isopropyl, A
is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
R.sup.2 is 3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro; R.sup.2 is
3-amino-5-(N-(2-phenyl-2-propyl)amidocarbonyl)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro; R.sup.2 is
3-amino-5-(N-(2,4-dichlorobenzyl)amidocarbonyl)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro; R.sup.2 is
3-amino-5-(N-(4-bromobenzyl)amidocarbonyl)phenyl, B is isopropyl, A
is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl,
A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
R.sup.2 is 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro; R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro; R.sup.2 is
3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl, B is isopropyl,
A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
R.sup.2 is 3-amino-5-(N-(3-trifluoromethylbenzyl)amidocarbonyl)ph-
enyl, B is isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and
X.sup.0 is chloro; R.sup.2 is
3-amino-5-(N-isobutylamidocarbonyl)phenyl, B is isopropyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-amino-5-(N-cyclobutylamidocarbonyl)phenyl, B is isopropyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-amino-5-(N-cyclopentylamidocarbonyl)phenyl, B is isopropyl, A is
a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2
is 3-amino-5-(N-cycloheptylamidocarbonyl)phenyl, B is isopropyl, A
is a bond, Y .sup.0is 4-amidinobenzyl, and X.sup.0 is chloro;
R.sup.2 is 3-amino-5-(N-(2-pyridylmethyl)amidocarbonyl)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro; R.sup.2 is
3-amino-5-(N-(3-pyridylmethyl)amidocarbonyl)phenyl, B is isopropyl,
A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
R.sup.2 is 3-amino-5-(N-(2-(4-methoxyphenyl)ethyl)amidocarbonyl)p-
henyl, B is isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and
X.sup.0 is chloro; R.sup.2 is
3-amino-5-(N-(3-phenylpropyl)amidocarbonyl)- phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro; R.sup.2 is 3-amino-5-(N-(2,2-diphenylethyl)amidocarbon-
yl)phenyl, B is isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is chloro; R.sup.2 is
3-amino-5-(N-(2-naphthylmethyl)amidocarbony- l)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro; R.sup.2 is 3-amino-5-(N-(1,2,3,4-tetrahydronaphth-2-yl-
methyl)amidocarbonyl)-phenyl, B is isopropyl, A is a bond, Y.sup.0
is 4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-aminophenyl, B is 2-propyl, A is a bond, Y.sup.0 is
4amidino-3-fluorobenzyl, and X.sup.0 is hydrido; R.sup.2 is
3-carboxyphenyl, B is 2-propyl, A is a bond, Y .sup.0is
4-amidinobenzyl, and X.sup.0 is hydrido; R.sup.2 is 3-aminophenyl,
B is 2-propyl, A is a bond, Y.sup.0 is 4-amidino-3-fluorobenzyl,
and X.sup.0 is chloro; R.sup.2 is 3,5-diaminophenyl, B is
2,2,2-trifluoroethyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and
X.sup.0 is chloro; R.sup.2 is 3,5-diaminophenyl, B is (S)-2-butyl,
A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
R.sup.2 is 3,5-diaminophenyl, B is isopropyl, A is a bond, Y.sup.0
is 4-amidinobenzyl, and X.sup.0is chloro; R.sup.2 is
3,5-diaminophenyl, B is isopropyl, A is a bond, Y.sup.0 is
4-amidino-2-fluorobenzylbenzyl, and X.sup.0 is chloro; R.sup.2 is
3,5-diaminophenyl, B is ethyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3,5-diaminophenyl, B is ethyl, A is a bond, Y.sup.0 is
4-amidino-2-fluorobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-amino-5-carboxyphenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y
is 4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-amino-5-carboxyphenyl, B is (S)-2-butyl, A is a bond, Y.sup.0is
4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-amino-5-carboxyphenyl, B is isopropyl, A is a bond, Y.sup.0 is
4-amidino-2-fluorobenzylbenzyl, and X.sup.0 is chloro; R.sup.2 is
3-amino-5-carboxyphenyl, B is ethyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-amino-5-carboxyphenyl, B is ethyl, A is a bond, Y.sup.0 is
4amidino-2-fluorobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-amino-5-(N-benzylamidocarbonyl)phenyl, B is 2,2,2-trifluoroethyl,
A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
(S)-2-butyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0
is chloro; R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidino-2-fluorobenzylbenzyl,
and X.sup.0 is chloro; R.sup.2 is
3-amino-5-(N-benzylamidocarbonyl)phenyl, B is ethyl, A is a bond,
is 4-amidinobenzyl, and X.sup.0 is chloro; R.sup.2 is
3-amino-5-(N-benzylamidocarbonyl)phenyl, B is ethyl, A is a bond,
Y.sup.0 is 4amidino-2-fluorobenzyl, and X.sup.0 is chloro; and
R.sup.2 is 3,5-diaminophenyl, B is isopropyl, A is a bond, Y.sup.0
is 4-amidinobenzylbenzyl, and X.sup.0 is hydrido.
45. Compound of claim 22 of the Formula: 112or a pharmaceutically
acceptable salt thereof, wherein; B is a C3-C7 cycloalkyl or a
C4-C6 saturated heterocyclyl, wherein each ring carbon is
optionally substituted with R.sup.33, a ring carbon other than the
ring carbon at the point of attachment of B to A is optionally
substituted with oxo provided that no more than one ring carbon is
substituted by oxo at the same time, ring carbons and a nitrogen
adjacent to the carbon atom at the point of attachment are
optionally substituted with R.sup.9 or R.sup.13, a ring carbon or
nitrogen adjacent to the R.sup.9 position and two atoms from the
point of attachment is optionally substituted with R.sup.10, a ring
carbon or nitrogen adjacent to the R.sup.13 position and two atoms
from the point of attachment is optionally substituted with
R.sup.12, a ring carbon or nitrogen three atoms from the point of
attachment and adjacent to the R.sup.10 position is optionally
substituted with R.sup.11, a ring carbon or nitrogen three atoms
from the point of attachment and adjacent to the R.sup.12 position
is optionally substituted with R.sup.33, and a ring carbon or
nitrogen four atoms from the point of attachment and adjacent to
the R.sup.11 and R.sup.33 positions is optionally substituted with
R.sup.34; R.sup.9, R.sup.11, and R.sup.13 are independently
selected from the group consisting of hydrido, hydroxy, amino,
amidino, guanidino, alkylamino, alkylthio, alkylsulfonamido,
alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkyl, alkoxy, halo,
haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboxy,
carboxamido, and cyano; R.sup.10 and R.sup.12 are independently
selected from the group consisting of hydrido, acetamido,
haloacetamido, amidino, guanidino, alkyl, aryl, aralkyl,
cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkoxy,
cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy,
heteroaralkoxy,heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino,
alkoxyamino, alkylamino, arylamino, aralkylamino, heteroarylamino,
heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino,
alkylsulfonamido, amidosulfonyl, arylsulfinyl, aralkylsulfinyl,
cycloalkylsulfinyl, heteroarylsulfinyl, arylsulfonyl,
aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl,
hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy,
carboxyalkyl, carboxamido, halo, haloalkyl, and cyano; R.sup.33 and
R.sup.34 are independently selected from the group consisting of
hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy,
hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl,
alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl,
carboalkoxy, carboxy, carboxamido, and cyano; R.sup.33 is
optionally Q.sup.b; A is a bond or
(CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr wherein rr is 0 or 1, pa is
an integer selected from 0 through 3, and W.sup.7 is (R.sup.7)NC(O)
or N(R.sup.7); R.sup.7is selected from the group consisting of
hydrido, hydroxy and alkyl; R.sup.15 is selected from the group
consisting of hydrido, halo, alkyl and haloalkyl; X.sup.o is
selected from the group consisting of hydrido, hydroxy,
hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl,
alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl,
haloalkoxy, and halo; R.sup.2 is Z.sup.0-Q; Z.sup.0 is selected
from the group consisting of a bond, CH.sub.2, CH.sub.2CH.sub.2,
W.sup.0--(CH(R.sup.42))p wherein p is 0 or 1 and W.sup.0 is
selected from the group consisting of O, S, and N(R.sup.41);
R.sup.41 and R.sup.42 are independently hydrido or alkyl; Q is
phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon
adjacent to the carbon at the point of attachment of said phenyl or
heteroaryl ring to Z.sup.0 is optionally substituted by R.sup.9,
the other carbon adjacent to the carbon at the point of attachment
is optionally substituted by R.sup.13, a carbon adjacent to R.sup.9
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.10, a carbon adjacent to R.sup.13
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.12, and any carbon adjacent to both
R.sup.10 and R.sup.12 is optionally substituted by R.sup.11;
Y.sup.0 is phenyl or a heteroaryl of 5 or 6 ring members, wherein
one carbon of said phenyl or said heteroaryl is substituted by
Q.sup.s, a carbon two or three atoms from the point of attachment
of Q.sup.s to said phenyl or said heteroaryl is substituted by
Q.sup.b, a carbon adjacent to the point of attachment of Q.sup.s is
optionally substituted by R.sup.17, another carbon adjacent to the
point of attachment of Q.sup.s is optionally substituted by
R.sup.18, a carbon adjacent to Q.sup.b is optionally substituted by
R.sup.16, and another carbon adjacent to Q.sup.b is optionally
substituted by R.sup.19; R.sup.16, R.sup.17, R.sup.18, and R.sup.19
are independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl,
haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,
aminoalkyl, and cyano; R.sup.16 or R.sup.19 is optionally
NR.sup.20R.sup.21 or and C(NR.sup.25)NR.sup.23R.sup.24, with the
proviso that R.sup.16, R.sup.19, and Q.sup.b are not simultaneously
hydrido; Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, hydrido, and C(NR.sup.25)NR.sup.23R.sup.24, with
the proviso that no more than one of R.sup.20 and R.sup.21 is
hydroxy at the same time and with the further proviso that no more
than one of R.sup.23 and R.sup.24 is hydroxy at the same time;
R.sup.20, R.sup.21, R.sup.23, R.sup.24, and R.sup.25 are
independently selected from the group consisting of hydrido, alkyl,
and hydroxy; Q.sup.s is selected from the group consisting of a
bond, CH.sub.2, and CH.sub.2CH.sub.2.
46. Compound of claim 45 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
cyclopropyl, cyclobutyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl,
azetidin-3-yl, thiaetan-3-yl, cyclopentyl, cyclohexyl, norbornyl,
7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl,
cycloheptyl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl,
1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl,
3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl,
3-pyrrolidinyl, 2-dioxanyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-pyranyl,
4H-pyran-4-one-2-yl, 4H-pyran-4one-3-yl, 2-tetrahydrofuranyl,
3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl,
4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl,
wherein each ring carbon is optionally substituted with R.sup.33,
ring carbons and a nitrogen adjacent to the carbon atom at the
point of attachment are optionally substituted with R.sup.9 or
R.sup.13, a ring carbon or nitrogen adjacent to the R.sup.9
position and two atoms from the point of attachment is optionally
substituted with R.sup.10, and a ring carbon or nitrogen adjacent
to the R.sup.13 position and two atoms from the point of attachment
is optionally substituted with R.sup.12; R.sup.9, R.sup.11, and
R.sup.13 are independently selected from the group consisting of
hydrido, amidino, guanidino, carboxy, methyl, ethyl, propyl,
isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,
N-methylamino, N,N-dimethylamino, N-ethylamino, methylthio,
ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl,
N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,
2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;
R.sup.10 and R.sup.12 are independently selected from the group
consisting of hydrido, amidino, guanidino, carboxy, carboxymethyl,
methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy,
propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido,
trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,
N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,
amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,
amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl,
N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl,
N-(3-fluorobenzyl)amidocarbonyl,
N-(2-trifluoromethylbenzyl)amidocarbonyl- ,
N-(1-phenylethyl)amidocarbonyl,
N-(1-methyl-1-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl,
N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl,
N-isopropylamidocarbonyl, N-propylamidocarbonyl,
N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,
N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl,
N-cyclohexylamidocarbonyl, fluoro, chloro, bromo, cyano,
cyclobutoxy, cyclohexoxy, cyclohexylmethoxy,
4-trifluoromethycyclohexylmethoxy, cyclopentoxy, benzyl, benzyloxy,
4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy,
4-bromobenzylamino, 5-bromopyrid-2-ylmethylamino,
4-butoxyphenamino, 3-chlorobenzyl, 4-chlorophenoxy,
4-chloro-3-ethylphenoxy, 4-chloro-3-ethylbenzylamino,
4-chloro-3-ethylphenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy,
4-chlorobenzylsulfonyl, 4-chlorophenylamino,
4-chlorophenylsulfonyl, 5-chloropyrid-3-yloxy,
2-cyanopyrid-3-yloxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy,
3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorophenoxy,
3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy,
2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy,
3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyloxy,
3,5-dimethylbenzyloxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy,
3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy,
4-fluorobenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy,
3-fluoro-5-trifluoromethyl benzyloxy,
4-fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethy-
lbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy,
2-fluoro-3-trifluoromethylph- enoxy, 2-fluorobenzyloxy,
4-fluorophenylamino, 2-fluoro-4-trifluoromethylp- henoxy,
4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy,
4-isopropyl-3-methylphenoxy, 4-isopropylbenzyloxy,
3-isopropylphenoxy, 4-isopropylphenoxy,
4-isopropyl-3-methylphenoxy, phenylamino, 1-phenylethoxy,
2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino, phenylsulfonyl,
3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy,
3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy,
3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy,
2,4-bis-trifluoromethylbenzyloxy, 3-trifluoromethylbenzyl,
3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy,
3-trifluoromethylphenoxy, 3-trifluoromethylthiobenzyloxy,
4-trifluoromethylthiobenzyloxy, 2,3,4-trifluorophenoxy,
2,3,5-trifluorophenoxy, 3-pentafluoroethylphenoxy,
3-(1,1,2,2-tetrafluoroethoxy)phenoxy, and
3-trifluoromethylthiophenoxy; R.sup.33 is selected from the group
consisting of hydrido, amidino, guanidino, carboxy, methoxy,
ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino,
ethoxyamino, acetamido, trifluoroacetamido, N-methylamino,
dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,
N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,
methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and
Q.sup.b; A is selected from the group consisting of a bond, NH,
N(CH.sub.3), N(OH), CH.sub.2, CH.sub.3CH, CF.sub.3CH, NHC(O),
N(CH.sub.3)C(O), C(O)NH, C(O)N(CH.sub.3), CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2, CH.sub.3CHCH.sub.2, and
CF.sub.3CHCH.sub.2; X.sup.o is selected from the group consisting
of hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl,
l-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino,
methylthio, ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy,
fluoro, chloro, and bromo; R.sup.2 is Z.sup.0-Q; Z.sup.0 is
selected from the group consisting of a bond, CH.sub.2,
CH.sub.2CH.sub.2, O, S, NH, N(CH.sub.3), OCH.sub.2, SCH.sub.2,
N(H)CH.sub.2, and N(CH.sub.3)CH.sub.2; Q.sup.s is selected from the
group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl,
2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl,
4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl,
3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl,
5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and
1,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at the
point of attachment of said phenyl or heteroaryl ring to Z.sup.0 is
optionally substituted by R.sup.9, the other carbon adjacent to the
carbon at the point of attachment is optionally substituted by
R.sup.13, a carbon adjacent to R.sup.9 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.10, a carbon adjacent to R.sup.13 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.12, and any carbon adjacent to both R.sup.10 and R.sup.12 is
optionally substituted by R.sup.11; Y.sup.0 is selected from the
group consisting of: 1-Q.sup.b-4-Q.sup.s-2-R-
.sup.16-3-R.sup.17-5-R.sup.18-6-R.sup.19 benzene,
2-Q.sup.b-5-Q.sup.s-6-R.- sup.17-4-R.sup.18-3-R.sup.19 pyridine,
3-Q.sup.b-6-Q.sup.s-2-R.sup.16-5-R.- sup.18-4-R.sup.19 pyridine,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-6-R.sup.18 pyrazine,
3-Q.sup.b-6-Q.sup.s-2-R.sup.18-5-R.sup.18-4-R.sup.19 pyridazine,
2Q.sup.b-5-Q.sup.s-4-R.sup.17-6-R.sup.18 pyrimidine,
5Q.sup.b-2-Q.sup.s-4-R.sup.16-6-R.sup.19 pyrimidine,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 thiophene,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 thiophene,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 furan,
2-Q.sup.b-5-Q.sup.s-3-R.- sup.16-4-R.sup.17 furan,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 pyrrole,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4R.sup.17 pyrrole,
4-Q.sup.b-2-Q.sup.s-5-R.sup.19 imidazole,
2-Q.sup.b-4Q.sup.s-5-R.sup.17 imidazole,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16 isoxazole,
5-Q.sup.b-3-Q.sup.s-4-R.sup.16 isoxazole,
2-Q.sup.b-5-Q.sup.s-4-R.sup.16 pyrazole,
4Q.sup.b-2-Q.sup.s-5-R.sup.19 thiazole, and
2-Q.sup.b-5-Q.sup.s-4R.sup.17 thiazole; R.sup.16, R.sup.17,
R.sup.18, and R.sup.19 are independently selected from the group
consisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy,
amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy,
amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,
dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,
trifluoromethylthio, methylsulfinyl, ethylsulfinyl,
methylsulfonyl-, ethylsulfonyl, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, and cyano; R.sup.16
or R.sup.19 is optionally C(NR.sup.25)NR.sup.23R.sup.24 with the
proviso that R.sup.16, R.sup.19, and Q.sup.b are not simultaneously
hydrido; Q.sup.b is C(NR.sup.25)NR.sup.23R.sup.24 or hydrido, with
the proviso that no more than one of R.sup.23 and R.sup.24 is
hydroxy at the same time; R.sup.23, R.sup.24, and R.sup.25 are
independently selected from the group consisting of hydrido,
methyl, ethyl, and hydroxy; Q.sup.s is selected from the group
consisting of a bond, CH.sub.2 and CH.sub.2CH.sub.2.
47. Compound of claim 46 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,
oxalan-2-yl, 2-(2R)-bicyclo[2.2.1]-heptyl, 1-pyrrolidinyl,
1-piperidinyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl,
azetidin-3-yl, 7-oxabicyclo[2.2.1]heptan-2-- yl,
bicyclo[3.1.0]hexan-6yl, 2-morpholinyl, 3-morpholinyl,
4-morpholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl,
2-piperidinyl, 3-piperidinyl, 4piperidinyl, 1-pyrrolidinyl,
2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 4H-2-pyranyl,
4H-3-pyranyl, 4H4-pyranyl, 4H-pyran4-one-2-yl, 4H-pyran-4one-3-yl,
2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl,
3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and
3-tetrahydrothienyl; A is selected from the group consisting of a
bond, CH.sub.2, NHC(O), CH.sub.2CH.sub.2, and
CH.sub.2CH.sub.2CH.sub.2; X.sup.o is selected from the group
consisting of hydrido, hydroxy, amino, amidino, hydroxyamino,
aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy,
hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro,
and chloro; R.sup.2 is Z.sup.0-Q; Z.sup.0 is selected from the
group consisting of a bond, CH.sub.2, O, S, NH, N(CH.sub.3),
OCH.sub.2, and SCH.sub.2; Q.sup.s is selected from the group
consisting of 3-amidocarbonyl-5-aminophenyl,
3-amino-5-(N-benzylamidocarbonyl)phenyl, 3-amino-5-benzylphenyl,
3-amino-5-(2-phenylethyl)phenyl, 3-amino-5-benzylaminophenyl,
3-amino-5-(2-phenylethylamino)phenyl, 3-amino-5-benzyloxyphenyl,
3-amino-5-(2-phenylethoxy)phenyl,
3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-methyl-- 1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-benzylamidosulfonyl)pheny- l,
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl,
3-amino-5-(N-ethylamidocarbonyl)phenyl,
3-amino-5-(N-isopropylamidocarbon- yl)phenyl,
3-amino-5-(N-propylamidocarbonyl)phenyl,
3-amino-5-(N-isobutylamidocarbonyl)phenyl,
3-amino-5-(N-(2-butyl)amidocar- bonyl)phenyl,
3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,
3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,
3-amino-5-(N-cyclohexylamid- ocarbonyl)phenyl,
5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl,
5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl,
3-amino-2-methylphenyl, 5amino-2-methylthiophenyl, 3-aminophenyl,
3-amino-5-(4-trifluoromethylben- zylamino)phenyl,
3-amino-5-(4-trifluoromethylbenzyloxy)phenyl, 3-carboxyphenyl,
3-carboxy-5-hydroxyphenyl, 3-amino-5-carboxyphenyl, 3-chlorophenyl,
2-chlorophenyl, 3-cyanophenyl, 3,-diaminophenyl,
3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,
2-hydroxyphenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl,
2-methoxyphenyl, 3-methoxyphenyl, 3-methoxyaminophenyl,
3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl,
2-methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl,
3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl,
2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl,
3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl;
Y.sup.0 is selected from the group consisting of:
1-Q.sup.b-4-Q.sup.s-2-R.sup.16-3-R.sup.17-5-R.sup.18-6-R.sup.19
benzene, 2-Q.sup.b-5-Q.sup.s-6-R.sup.17-4-R.sup.18-3-R.sup.19
pyridine, 3-Q.sup.b-6-Q.sup.s-2-R.sup.16-5-R.sup.18-4-R.sup.19
pyridine, 3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 thiophene, and
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 thiophene; R.sup.16 and
R.sup.19 are independently selected from the group consisting of
hydrido, amidino, amino, aminomethyl, methoxy, methylamino,
hydroxy, hydroxymethyl, fluoro, chloro, and cyano; R.sup.16 or
R.sup.19 is optionally C(NR.sup.25)NR.sup.23R.sup.24 with the
proviso that R.sup.16, R.sup.19, and Q.sup.b are not simultaneously
hydrido; R.sup.17 and R.sup.18 are independently selected from the
group consisting of hydrido, fluoro, chloro, hydroxy,
hydroxymethyl, amino, carboxy, and cyano; Q.sup.b is
C(NR.sup.25)NR.sup.23R.sup.24 or hydrido; R.sup.23, R.sup.24, and
R.sup.25 are independently hydrido or methyl; Q.sup.s is
CH.sub.2.
48. Compound of claim 45 of the Formula: 113or a pharmaceutically
acceptable salt thereof, wherein; B is a C3-C7 cycloalkyl or a
C4-C6 saturated heterocyclyl, wherein each ring carbon is
optionally substituted with R.sup.33, a ring carbon other than the
ring carbon at the point of attachment of B to A is optionally
substituted with oxo provided that no more than one ring carbon is
substituted by oxo at the same time, ring carbons and a nitrogen
adjacent to the carbon atom at the point of attachment are
optionally substituted with R.sup.9 or R.sup.13, a ring carbon or
nitrogen adjacent to the R.sup.9 position and two atoms from the
point of attachment is optionally substituted with R.sup.10, a ring
carbon or nitrogen adjacent to the R.sup.13 position and two atoms
from the point of attachment is optionally substituted with
R.sup.12, a ring carbon or nitrogen three atoms from the point of
attachment and adjacent to the R.sup.10 position is optionally
substituted with R.sup.11, a ring carbon or nitrogen three atoms
from the point of attachment and adjacent to the R.sup.12 position
is optionally substituted with R.sup.33, and a ring carbon or
nitrogen four atoms from the point of attachment and adjacent to
the R.sup.11 and R.sup.33 positions is optionally substituted with
R.sup.34; R.sup.9, R.sup.11, and R.sup.13 are independently
selected from the group consisting of hydrido, hydroxy, amino,
amidino, guanidino, alkylamino, alkylthio, alkoxy, alkylsulfinyl,
alkylsulfonyl, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,
hydroxyalkyl, carboxy, carboxamido, and cyano; R.sup.10 and
R.sup.12 are independently selected from the group consisting of
hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl,
alkoxy, alkoxyamino, hydroxy, amino, alkylamino, alkylsulfonamido,
amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl,
carboalkoxy, carboxy, carboxamido, carboxyalkyl, and cyano;
R.sup.33 and R.sup.34 are independently selected from the group
consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino,
alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,
hydroxyalkyl, carboalkoxy, carboxy, carboxamido, and cyano;
R.sup.33 is optionally Q.sup.b; A is a bond or
(CH(R.sup.15)).sub.pa--(W.sup.7).sub.r- r wherein rr is 0or 1, pa
is an integer selected from 0 through 3, and W.sup.7 is N(R.sup.7);
R.sup.7 is hydrido or alkyl; R.sup.15 is selected from the group
consisting of hydrido, halo, alkyl, and haloalkyl; X.sup.o is
selected from the group consisting of hydrido, hydroxy,
hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl,
alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl,
haloalkoxy, and halo; R.sup.2 is Z.sup.0-Q; Z.sup.0 is a bond; Q is
phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon
adjacent to the carbon at the point of attachment of said phenyl or
heteroaryl ring to Z.sup.0 is optionally substituted by R.sup.9,
the other carbon adjacent to the carbon at the point of attachment
is optionally substituted by R.sup.13, a carbon adjacent to R.sup.9
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.10, a carbon adjacent to R.sup.13
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.12, and any carbon adjacent to both
R.sup.10 and R.sup.12 is optionally substituted by R.sup.11;
Y.sup.0 is phenyl or a heteroaryl of 5 or 6 ring members, wherein
one carbon of said phenyl or said heteroaryl is substituted by
Q.sup.s, a carbon two or three atoms from the point of attachment
of Q.sup.s to said phenyl or said heteroaryl is substituted by
Q.sup.b, a carbon adjacent to the point of attachment of Q.sup.s is
optionally substituted by R.sup.17, another carbon adjacent to the
point of attachment of Q.sup.s is optionally substituted by
R.sup.18, a carbon adjacent to Q.sup.b is optionally substituted by
R.sup.16, and another carbon adjacent to Q.sup.b is optionally
substituted by R.sup.19; R.sup.16, R.sup.17, R.sup.18, and R.sup.19
are independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl,
haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,
aminoalkyl, and cyano; R.sup.16or R.sup.19 is optionally
NR.sup.20R.sup.21 or C(NR.sup.25)NR.sup.23R.sup.24, with the
proviso that R.sup.16, R.sup.19, and Q.sup.b are not simultaneously
hydrido; Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, hydrido, and C(NR.sup.25)NR.sup.23R.sup.24;
R.sup.20, R.sup.21, R.sup.23, R.sup.24, and R.sup.25 are
independently hydrido or alkyl; Q.sup.s is CH.sub.2.
49. Compound of claim 48 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,
oxalan-2-yl, 2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl,
azetidin-1-yl, azetidin-2-yl, azetidin-3-yl,
bicyclo[3.1.0]hexan-6-yl, 2-morpholinyl, 3-morpholinyl,
4-morpholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl,
2-piperidinyl, 3-piperidinyl, 4piperidinyl, 1-pyrrolidinyl,
2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 2-tetrahydrofuranyl,
3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl,
4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl,
wherein each ring carbon is optionally substituted with R.sup.33,
ring carbons and a nitrogen adjacent to the carbon atom at the
point of attachment are optionally substituted with R.sup.9 or
R.sup.13, a ring carbon or nitrogen adjacent to the R.sup.9
position and two atoms from the point of attachment are optionally
substituted with R.sup.10, and a ring carbon or nitrogen atom
adjacent to the R.sup.13 position and two atoms from the point of
attachment is optionally substituted with R.sup.12; R.sup.9,
R.sup.11, and R.sup.13 are independently selected from the group
consisting of hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy,
amino, N-methylamino, N,N-dimethylamino, methylthio,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro,
chloro, bromo, amidosulfonyl, N-methylamidosulfonyl,
N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,
amidocarbonyl, N-methylamidocarbonyl, carboxy, and cyano; R.sup.10
and R.sup.12 are independently selected from the group consisting
of hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl,
N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarb- onyl,
N-(3-fluorobenzyl)amidocarbonyl,
N-(2-trifluoromethylbenzyl)amidocar- bonyl,
N-(1-phenylethyl)amidocarbonyl,
N-(1-methyl-1-phenylethyl)amidocarb- onyl, N-benzylamidosulfonyl,
N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl,
N-isopropylamidocarbonyl, N-propylamidocarbonyl,
N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,
N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl,
N-cyclohexylamidocarbonyl, guanidino, methyl, ethyl, methoxy,
ethoxy, hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
carboxy, carboxymethyl, amino, acetamido, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido,
aminomethyl, N-methylamino, dimethylamino, methoxyamino,
amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,
methanesulfonamido, methoxycarbonyl, fluoro, chloro, bromo, and
cyano; R.sup.33 is selected from the group consisting of hydrido,
amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy,
carboxy, amino, N-methylamino, dimethylamino, methoxyamino,
methylthio, ethylthio, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,
N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, cyano, and
Q.sup.b; A is selected from the group consisting of a bond, NH,
N(CH.sub.3), CH.sub.2, CH.sub.3CH, CH.sub.2CH.sub.2, and
CH.sub.2CH.sub.2CH.sub.2; X.sup.o is selected from the group
consisting of hydrido, hydroxy, amino, amidino, aminomethyl, cyano,
methyl, trifluoromethyl, hydroxymethyl, chloro, and fluoro; R.sup.2
is selected from the group consisting of phenyl, 2-thienyl,
2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl,
2-pyridyl, and 3-pyridyl, wherein a carbon adjacent to the carbon
at the point of attachment of said phenyl or heteroaryl ring to the
1,4-quinone ring is optionally substituted by R.sup.9, the other
carbon adjacent to the carbon at the point of attachment is
optionally substituted by R.sup.13, a carbon adjacent to R.sup.9
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.10, a carbon adjacent to R.sup.13
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.12, and any carbon adjacent to both
R.sup.10 and R.sup.12 is optionally substituted by R.sup.11;
Y.sup.0 is selected from the group consisting of:
1-Q.sup.b-4-Q.sup.s-2R.sup.16-3-R.- sup.17-5-R.sup.18-6-R.sup.18
benzene, 2-Q.sup.b-5-Q.sup.s-6-R.sup.17-4-R.s- up.18-3-R.sup.19
pyridine, 2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 thiophene,
3-Q.sup.b-6-Q.sup.s-2-R.sup.16-5-R.sup.18-4-R.sup.19 pyridine,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 thiophene,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 furan,
2-Q.sup.b-5-Q.sup.s-3-R.- sup.16-4R.sup.17 furan,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 -pyrrole,
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4R.sup.17 pyrrole,
4-Q.sup.b-2-Q.sup.s-5-R.sup.19 thiazole, and
2-Q.sup.b-5-Q.sup.s-4-R.sup.- 17 thiazole; R.sup.16, R.sup.17,
R.sup.18, and R.sup.19 are independently selected from the group
consisting of hydrido, methyl, ethyl, amidino, guanidino, methoxy,
hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl,
N-methylamino, dimethylamino, methylthio, ethylthio,
trifluoromethylthio, methylsulfinyl, methylsulfonyl,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,
trifluoromethoxy, fluoro, chloro, hydroxymethyl, carboxy, and
cyano; Q.sup.b is NR.sup.20R.sup.21 or
C(NR.sup.25)NR.sup.23R.sup.24; R.sup.20, R.sup.21, R.sup.23,
R.sup.24, and R.sup.25 are independently selected from the group
consisting of hydrido, methyl, and ethyl; Q.sup.s is CH.sub.2.
50. Compound of claim 49 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxalan-2-yl,
2-(2R)-bicyclo[2.2.1]-h- eptyl, oxetan-3-yl, azetidin-1-yl,
azetidin-2-yl, azetidin-3-yl, 1-pyrrolidinyl and 1-piperidinyl; A
is selected from the group consisting of a bond, CH.sub.2,
CH.sub.2CH.sub.2 and CH.sub.2CH.sub.2CH.sub.2; X.sup.o is selected
from the group consisting of hydrido, hydroxy, amino, amidino,
aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, and
fluoro; R.sup.2 is selected from the group consisting of
3-amidocarbonyl-5-aminophenyl, 3-amidocarbonyl-5-aminophenyl,
3-amino-5-(N-benzylamidocarbonyl)phenyl,
3-amino-5-(N-(2-chlorobenzyl )amidocarbonyl)phenyl,
3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-methyl-- 1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-benzylamidosulfonyl)pheny- l,
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl,
3-amino-5-(N-ethylamidocarbonyl)phenyl,
3-amino-5-(N-isopropylamidocarbon- yl)phenyl,
3-amino-5-(N-propylaniidocarbonyl)phenyl,
3-amino-5-(N-isobutylamidocarbonyl)phenyl,
3-amino-5-(N-(2-butyl)amidocar- bonyl)phenyl,
3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,
3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,
3-amino-5-(N-cyclohexylamid- ocarbonyl)phenyl,
5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl,
5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl,
3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl,
3-carboxyphenyl, 3-carboxy-5-aminophenyl,
3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl,
3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl,
3-chlorophenyl, 2-chlorophenyl, 3-cyanophenyl, 3,5-diaminophenyl,
3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,
2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,
3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,
3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,
3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl,
4-methylphenyl, phenyl, 3-trifluoroacetamidophenyl,
3-trifluoromethylphenyl, 2-trifluoromethylphenyl,
5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl,
4pyridyl, 2-thienyl, and 3-thienyl; Y.sup.0 is selected from the
group consisting of: 1-Q.sup.b-4-Q.sup.s-2-R.sup.16--
3-R.sup.17-5-R.sup.18-6-R.sup.19 benzene,
2-Q.sup.b-5-Q.sup.s-6-R.sup.17-4- -R.sup.18-3-R.sup.19 pyridine,
3-Q.sup.b-6-Q.sup.s-2-R.sup.16-5-R.sup.18-4- -R.sup.19 pyridine,
3-Q.sup.b-5-Q.sup.s-4-R.sup.16-2-R.sup.19 thiophene, and
2-Q.sup.b-5-Q.sup.s-3-R.sup.16-4-R.sup.17 thiophene; R.sup.16 and
R.sup.19 are independently selected from the group consisting of
hydrido, amidino, amino, aminomethyl, methoxy, methylamino,
hydroxy, hydroxymethyl, fluoro, chloro, and cyano; R.sup.17 and
R.sup.18 are independently selected from the group consisting of
hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy,
and cyano; Q.sup.b is C(NR.sup.25)NR.sup.23R.sup.24; R.sup.23,
R.sup.24, and R.sup.25 are independently hydrido or methyl; Q.sup.s
is CH.sub.2.
51. Compound of claim 50 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxalan-2-yl,
2-(2R)-bicyclo[2.2.1]-h- eptyl, oxetan-3-yl, azetidin-1-yl,
azetidin-2-yl, azetidin-3-yl, and 1-piperidinyl; A is selected from
the group consisting of a bond, CH.sub.2, CH.sub.2CH.sub.2 and
CH.sub.2CH.sub.2CH.sub.2; X.sup.o is selected from the group
consisting of hydrido, hydroxy, amino, amidino, aminomethyl, cyano,
methyl, trifluoromethyl, hydroxymethyl, and fluoro; R.sup.2 is
selected from the group consisting of 3-amidocarbonyl-5-aminop-
henyl, 3-amino-5-(N-benzylamidocarbonyl)phenyl,
3-amino-5-(N-(2-chlorobenz- yl)amidocarbonyl)phenyl,
3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl- ,
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-methyl-- 1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-benzylamidosulfonyl)pheny- l,
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl,
3-amino-5-(N-ethylamidocarbonyl)phenyl,
3-amino-5-(N-isopropylamidocarbon- yl)phenyl,
3-amino-5-(N-propylamidocarbonyl)phenyl,
3-amino-5-(N-isobutylamidocarbonyl)phenyl,
3-amino-5-(N-(2-butyl)amidocar- bonyl)phenyl,
3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,
3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,
3-amino-5-(N-cyclohexylamid- ocarbonyl)phenyl, 3-aminophenyl,
3-carboxy-5-aminophenyl, 3-chlorophenyl, 3,5-diaminophenyl,
3-dimethylaminophenyl, 3-hydroxyphenyl,
3-methanesulfonylaminophenyl, 3-methylaminophenyl, 2-methylphenyl,
3-methylphenyl, phenyl, 3-trifluoroacetamidophenyl,
3-bromo-2-thienyl, 2-thienyl, and 3-thienyl; Y.sup.0 is selected
from the group consisting of 5-amidino-2-thienylmethyl,
4-amidinobenzyl, 2-fluoro-4-amidinobenzyl, and
3-fluoro-4-amidinobenzyl.
52. Compound of claim 45 where said compound is selected from the
group of the Formula: 114or a pharmaceutically acceptable salt
thereof, wherein B, A, R.sup.2, X.sup.o, and Y.sup.0 are selected
to form a compound selected from the group consisting of; R.sup.2
is 3-aminophenyl, B is cyclopropyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.o is chloro; R.sup.2 is 3-aminophenyl, B
is cyclobutyl, A is a bond, Y.sup.0 is 4-amidino-2-fluorobenzyl,
and X.sup.o is chloro; R.sup.2 is 3-aminophenyl, B is cyclobutyl, A
is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.o is chloro;
R.sup.2 is 3-aminophenyl, B is cyclopropyl, A is a bond, Y.sup.0 is
4-amidino-2-fluorobenzyl, and X.sup.o is chloro; R.sup.2 is
3-aminophenyl, B is cyclobutyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.o is hydrido; R.sup.2 is 3-aminophenyl,
B is cyclobutyl, A is a bond, Y.sup.0 is 4-amidino-3-fluorobenzyl,
and X.sup.o is chloro; R.sup.2 is 3-aminophenyl, B is cyclopentyl,
A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.o is chloro;
R.sup.2 is 5amino-2-thienyl, B is cyclobutyl, A is a bond, Y.sup.0
is 4-amidinobenzyl, and X.sup.o is chloro; R.sup.2 is
3-aminophenyl, B is cyclopropyl, A is CH.sub.2, Y.sup.0 is
4-amidinobenzyl, and X.sup.o is chloro; R.sup.2 is 3-aminophenyl, B
is 2-(2R)-bicyclo[2.2.1]-heptyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.o is chloro; R.sup.2 is 3-aminophenyl, B
is cyclopentyl, A is a bond, Y.sup.0 is 4-amidino-2-fluorobenzyl,
and X.sup.o is chloro; R.sup.2 is 3-aminophenyl, B is cyclohexyl, A
is CH.sub.2CH.sub.2,Y.sup.0 is 4-amidinobenzyl, and X.sup.o is
hydrido; R.sup.2 is 3-aminophenyl, B is oxalan-2-yl, A is
CH.sub.2,Y.sup.0 is 4-amidinobenzyl, and X.sup.o is chloro; R.sup.2
is 3-aminophenyl, B is 1-piperidinyl, A is CH.sub.2CH.sub.2,
Y.sup.0 is 4-amidinobenzyl, and X.sup.o is chloro; R.sup.2 is
3-aminophenyl, B is 1-pyrrolidinyl, A is CH.sub.2CH.sub.2CH.sub.2,
Y.sup.0 is 4-amidinobenzyl, and X.sup.o is chloro; R.sup.2 is
3-amino-5-carbomethoxyphenyl, B is cyclobutyl, A is a bond, Y.sup.0
is 4-amidinobenzyl, and X.sup.o is hydrido; R.sup.2 is
3-amino-5-carboxyphenyl, B is cyclobutyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.o is hydrido; R.sup.2 is
3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.o is hydrido; R.sup.2 is
2-amino-6carboxypyridy), B is cyclobutyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.o is hydrido; R.sup.2 is
3-amino-5-carbomethoxyphenyl, B is cyclobutyl, A is a bond, Y.sup.0
is 4-amidinobenzyl, and X.sup.o is chloro; R.sup.2 is
3-amino-5-carboxyphenyl, B is cyclobutyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.o is chloro; R.sup.2 is
3,5-diaminophenyl, B is cyclopropyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.o is chloro; R.sup.2 is
3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y.sup.0 is
4-amidino-2-fluorobenzyl, and X.sup.o is chloro; R.sup.2 is
3,5-diaminophenyl, B is cyclopropyl, A is a bond, Y.sup.0 is
4-amidino-2-fluorobenzyl, and X.sup.o is chloro; R.sup.2 is
3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.o is hydrido; R.sup.2 is
3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y.sup.0 is
4-amidino-3-fluorobenzyl, and X.sup.o is chloro; R.sup.2 is
3,5-diaminophenyl, B is cyclopentyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.o is chloro; R.sup.2 is
3-carboxy-5-aminophenyl, B is cyclopropyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.o is chloro; R.sup.2 is
3-carboxy-5-aminophenyl, B is cyclobutyl, A is a bond, Y.sup.0is
4-amidino-2-fluorobenzyl, and X.sup.o is chloro; R.sup.2 is
3-carboxy-5-aminophenyl, B is cyclopropyl, A is a bond, Y.sup.0 is
4-amidino-2-fluorobenzyl, and X.sup.o is chloro; R.sup.2 is
3-carboxy-5-aminophenyl, B is cyclobutyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.o is hydrido; R.sup.2 is
3-carboxy-5-aminophenyl, B is cyclobutyl, A is a bond, Y.sup.0 is
4-amidino-3-fluorobenzyl, and X.sup.o is chloro; R.sup.2 is
3-carboxy-5-aminophenyl, B is cyclopentyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.o is chloro; R.sup.2 is
3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclopropyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.o is chloro; R.sup.2 is
3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is a
bond, Y.sup.0 is 4-amidino-2-fluorobenzyl, and X.sup.o is chloro;
R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
cyclobutyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.o is
chloro; R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
cyclopropyl, A is a bond, Y.sup.0 is 4-amidino-2-fluorobenzyl, and
X.sup.o is chloro; R.sup.2 is
3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.o is hydrido; R.sup.2
is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is a
bond, Y.sup.0 is 4-amidino-3-fluorobenzyl, and X.sup.o is chloro;
R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
cyclopentyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.o
is chloro; R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is
cyclopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.o
is chloro; R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclobutyl,
A is a bond, Y.sup.0 is 4-amidino-2-fluorobenzyl, and X.sup.o is
chloro; R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclobutyl,
A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.o is chloro;
R.sup.2 is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is
cyclopropyl, A is a bond, Y.sup.0 is 4-amidino-2-fluorobenzyl, and
X.sup.o is chloro; R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)- phenyl, B is
cyclobutyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.o is
hydrido; R.sup.2 is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl-
)phenyl, B is cyclobutyl, A is a bond, Y.sup.0 is
4-amidino-3-fluorobenzyl- , and X.sup.o is chloro; R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulf- onyl)phenyl, B is
cyclopentyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.o
is chloro; R.sup.2 is 3-amino-5-(N-(2-trifluoromethylbenzyl)a-
midocarbonyl)-phenyl, B is cyclopropyl, A is a bond, Y.sup.0 is
4-amidinobenzyl, and X.sup.o is chloro; R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is
cyclobutyl, A is a bond, Y.sup.0 is 4-amidino-2-fluorobenzyl, and
X.sup.o is chloro; R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl- )-phenyl, B is
cyclobutyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.o is
chloro; R.sup.2 is 3-amino-5-(N-(2-trifluoromethylbenzyl)amido-
carbonyl)-phenyl, B is cyclopropyl, A is a bond, Y.sup.0 is
4-amidino-2-fluorobenzyl, and X.sup.o is chloro; R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is
cyclobutyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.o is
hydrido; R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-- phenyl, B is
cyclobutyl, A is a bond, Y.sup.0 is 4-amidino-3-fluorobenzyl, and
X.sup.o is chloro; and R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenz- yl)amidocarbonyl)-phenyl, B is
cyclopentyl, A is a bond, Y.sup.0 is amidinobenzyl, and X.sup.o is
chloro.
53. Compound of claim 22 of the Formula: 115or a pharmaceutically
acceptable salt thereof, wherein; B is phenyl or a heteroaryl of 5
or 6 ring members, wherein a carbon adjacent to the carbon at the
point of attachment of said phenyl or heteroaryl ring to A is
optionally substituted by R.sup.32, the other carbon adjacent to
the carbon at the point of attachment is optionally substituted by
R.sup.36, a carbon adjacent to R.sup.32 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.33, a carbon adjacent to R.sup.36 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.35, and any carbon adjacent to both R.sup.33 and R.sup.35 is
optionally substituted by R.sup.34; R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36 are independently selected from the group
consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy,
hydroxy, amino, alkoxyamino, haloalkanoyl, nitro, alkylamino,
alkylthio, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl,
heterocyclyl, alkylsulfonamido, amidosulfonyl, alkyl, alkenyl,
halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, alkylamino,
carboalkoxy, carboxy, carboxamido, cyano, and Q.sup.b; B is
optionally selected from the group consisting of hydrido,
trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8
alkynyl, and C2-C8 haloalkyl, wherein each member of group B is
optionally substituted at any carbon up to and including 6 atoms
from the point of attachment of B to A with one or more of the
group consisting of R.sup.32, R.sup.33, R.sup.34, R.sup.35, and
R.sup.36; B is optionally a C3-C12 cycloalkyl or a C4-C9 saturated
heterocyclyl, wherein each ring carbon is optionally substituted
with R.sup.33, a ring carbon other than the ring carbon at the
point of attachment of B to A is optionally substituted with oxo
provided that no more than one ring carbon is substituted by oxo at
the same time, ring carbons and a nitrogen adjacent to the carbon
atom at the point of attachment are optionally substituted with
R.sup.9 or R.sup.13, a ring carbon or nitrogen adjacent to the
R.sup.9 position and two atoms from the point of attachment is
optionally substituted with R.sup.10, a ring carbon or nitrogen
adjacent to the R.sup.13 position and two atoms from the point of
attachment is optionally substituted with R.sup.12, a ring carbon
or nitrogen three atoms from the point of attachment and adjacent
to the R.sup.10 position is optionally substituted with R.sup.11, a
ring carbon or nitrogen three atoms from the point of attachment
and adjacent to the R.sup.12 position is optionally substituted
with R.sup.33, and a ring carbon or nitrogen four atoms from the
point of attachment and adjacent to the R.sup.11 and R.sup.33
positions is optionally substituted with R.sup.34;
R.sup.9,R.sup.10,R.sup.11,R.sup.12, and R.sup.13 are independently
selected from the group consisting of hydrido, acetamido,
haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl, amidino,
guanidino, alkylenedioxy, haloalkylthio, alkoxy, cycloalkoxy,
cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy,
heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino, alkylamino,
N-alkyl-N-arylamino, arylamino, aralkylamino, heteroarylamino,
heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino,
alkylthio, alkylsulfinyl, arylsulfinyl, aralkylsulfinyl,
cycloalkylsulfinyl, heteroarylsulfinyl, alkylsulfamido,
alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl,
heteroarylsulfonyl, amidosulfonyl, alkyl, aryl, aralkyl,
cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, halo,
haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, aminnoalkyl,
carboalkoxy, carboxy, carboxyalkyl, carboxamido, and cyano; A is a
bond or (CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr wherein rr is 0 or
1, pa is an integer selected from 0 through 3, and W.sup.7 is
selected from the group consisting of O, S, C(O), (R.sup.7)NC(O),
(R.sup.7)NC(S), and N(R.sup.7); R.sup.7 is selected from the group
consisting of hydido, hydroxy and alkyl; R.sup.15 is selected from
the group consisting of hydrido, hydroxy, halo, alkyl, and
haloalkyl; X.sup.0 is selected from the group consisting of
hydrido, alkyl, cyano, halo, haloalkyl, haloalkoxy, amino,
aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy,
hydroxyalkyl, alkoxyamino, thiol, and alkylthio; R.sup.2 is
Z.sup.0-Q; Z.sup.0 is selected from the group consisting of a bond,
(CR.sup.41R.sup.42).sub.q wherein q is 1 or 2, and
(CH(R.sup.41)).sub.g--W.sup.0--(CH(R.sup.42)).sub.p wherein g and p
are integers independently selected from 0 through 3 and W.sup.0 is
selected from the group consisting of O, S, C(O), S(O),
N(R.sup.41), and ON(R.sup.41); Z.sup.0 is optionally
(CH(R.sup.41)).sub.e--W.sup.22--(CH(R- .sup.42)).sub.h wherein e
and h are independently 0 or 1 and W.sup.22 is selected from the
group consisting of CR.sup.41.dbd.CR.sup.42, 1,2-cyclopropyl,
1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl,
1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl,
3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl,
2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,
2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl,
1,2-pyrrolidinyl,1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,
2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, wherein Z.sup.0
is directly bonded to the 1,4quinone ring and W.sup.22 is
optionally substituted with one or more substituents selected from
the group consisting of R.sup.9,R.sup.10,R.sup.11,R.sup.12, and
R.sup.13; R.sup.41 and R.sup.42 are independently selected from the
group consisting of hydrido, hydroxy, alkyl, and amino; Q is phenyl
or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent
to the carbon at the point of attachment of said phenyl or
heteroaryl ring to Z.sup.0 is optionally substituted by R.sup.9,
the other carbon adjacent to the carbon at the point of attachment
is optionally substituted by R.sup.13, a carbon adjacent to R.sup.9
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.10, a carbon adjacent to R.sup.13
and two atoms from the carbon at the point of attachment is
optionally substituted by R.sup.12, and any carbon adjacent to both
R.sup.10 and R.sup.12 is optionally substituted by R.sup.11, with
the proviso that Q is other than a phenyl when Z.sup.0 is a bond; Q
is optionally hydrido with the proviso that Z.sup.0 is selected
from other than a bond; K is CHR.sup.4a wherein R.sup.4a is
selected from the group consisting of hydrido, hydroxyalkyl, alkyl,
alkoxyalkyl, alkylthioalkyl, and haloalkyl; E.sup.0 is selected
from the group consisting of a bond, C(O)N(H), (H)NC(O),
(R.sup.7)NS(O).sub.2, and S(O).sub.2N(R.sup.7); Y.sup.AT is
Q.sup.b-Q.sup.s; Q.sup.s is (CR.sup.37R.sup.38).sub.b wherein b is
an integer selected from 1 through 4, R.sup.37 is selected from the
group consisting of hydrido, alkyl, and haloalkyl, and R.sup.38 is
selected from the croup consisting of hydrido, alkyl, haloalkyl,
aroyl, and heteroaroyl with the proviso that there is at least one
aroyl or heteroaroyl substituent, with the further proviso that no
more than one aroyl or heteroaroyl is bonded to
(CR.sup.37R.sup.38).sub.b at the same time, with the still further
proviso that said aroyl and said heteroaroyl are optionally
substituted with one or more substituents selected from the group
consisting of R.sup.16,R.sup.17,R.sup.18, and R.sup.19, with
another further proviso that said aroyl and said heteroaroyl are
bonded to the CR.sup.37R.sup.38 that is directly bonded to E.sup.0,
with still another further proviso that no more than one alkyl or
one haloalkyl is bonded to a CR.sup.37R.sup.38 at the same time,
and with the additional proviso that said alkyl and haloalkyl are
bonded to a carbon other than the one bonding said aroyl or said
heteroaroyl; R.sup.16,R.sup.17,R.sup.1- 8, and R.sup.19 are
independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
alkoxyamino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,
alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy,
hydroxyalkyl, aminoalkyl, and cyano; R.sup.16 or R.sup.19 is
optionally selected from the group consisting of
NR.sup.20R.sup.21,N(R.sup.26)C(NR.sup.25)N(R.sup.- 23)(R.sup.24),
and C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that
R.sup.16,R.sup.19, and Q.sup.b are not simultaneously hydrido;
Q.sup.b is selected from the group consisting of NR.sup.20R.sup.21,
hydrido, N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24), and
C(NR.sup.25)NR.sup.23R.- sup.24, with the proviso that no more than
one of R.sup.20 and R.sup.21 is selected from the group consisting
of hydroxy, amino, alkylamino, and dialkylamino at the same time
and with the further proviso that no more than one of R.sup.23 and
R.sup.24 is selected from the group consisting of hydroxy, amino,
alkylamino, and dialkylamino at the same time;
R.sup.20,R.sup.21,R.sup.23,R.sup.24,R.sup.25, and R.sup.26 are
independently selected from the group consisting of hydrido, alkyl,
hydroxy, amino, alkylamino and dialkylamino.
54. Compound of claim 53 of the Formula: 116or a pharmaceutically
acceptable salt thereof, wherein; B is selected from the group
consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl,
2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl,
4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, and 5-isoxazolyl, wherein a
carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to A is optionally substituted by
R.sup.32, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.36, a carbon adjacent
to R.sup.32 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.33, a carbon adjacent
to R.sup.36 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.35, and any carbon
adjacent to both R.sup.33 and R.sup.35 is optionally substituted by
R.sup.34; R.sup.32,R.sup.33,R.sup.34,R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino,
N-methylamino, dimethylamino, methoxyamino, methylthio, ethylthio,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro,
chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl,
amidocarbonyl, carboxy, cyano, and Q.sup.b; B is optionally
selected from the group consisting of hydrido, ethyl, 2-propenyl,
2-propynyl, propyl, isopropyl, butyl, 2-butenyl, 2-butynyl,
sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl,
2-pentenyl, 3-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 3-pentyl,
2-methylbutyl, 2-methyl-2-butenyl, 3-methylbutyl,
3-methyl-2-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl,
2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl,
1-methyl-3-pentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl,
3-hexyl, 1-ethyl-2-butenyl, 1-heptyl, 2-heptenyl, 3-heptenyl,
4-heptenyl, 5-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl,
5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl,
1-methyl-4-hexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl,
1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl,
1-ethyl-3-pentenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl,
2,2,2-trifluoroethyl, 2,2-difluoropropyl,
4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl,
5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein each
member of group B is optionally substituted at any carbon up to and
including 5 atoms from the point of attachment of B to A with one
or more of the group consisting of
R.sup.32,R.sup.33,R.sup.34,R.sup.35, and R.sup.36; B is optionally
selected from the group consisting of cyclopropyl, cyclobutyl,
cyclopentyl, cyclohexyl, cycloheptyl, oxalan-2-yl,
2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl, azetidin-1-yl,
azetidin-2-yl, azetidin-3-yl, bicyclo[3.1.0]hexan-6-yl,
2-morpholinyl, 3-morpholinyl, 4morpholinyl, 1-piperazinyl,
2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl,
4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl,
2-dioxanyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl,
2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl,
2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring
carbon is optionally substituted with R.sup.33, ring carbons and a
nitrogen adjacent to the carbon atom at the point of attachment are
optionally substituted with R.sup.9 or R.sup.13, a ring carbon or
nitrogen adjacent to the R.sup.9 position and two atoms from the
point of attachment is optionally substituted with R.sup.10, and a
ring carbon or nitrogen adjacent to the R.sup.13 position and two
atoms from the point of attachment is optionally substituted with
R.sup.12; R.sup.9,R.sup.11, and R.sup.13 are independently selected
from the group consisting of hydrido, methyl, ethyl, methoxy,
ethoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino,
methylthio, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,
N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,
1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy, and
cyano; R.sup.10 and R.sup.12 are independently selected from the
group consisting of hydrido, amidino, amidocarbonyl,
N-methylamidocarbonyl, N-benzylamidocarbonyl,
N-(2-chlorobenzyl)amidocarb- onyl, N-(3-fluorobenzyl)amidocarbonyl,
N-(2-trifluoromethylbenzyl)amidocar- bonyl,
N-(1-phenylethyl)amidocarbonyl,
N-(1-methyl-1-phenylethyl)amidocarb- onyl, N-benzylamidosulfonyl,
N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl,
N-isopropylamidocarbonyl, N-propylamidocarbonyl,
N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,
N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl,
N-cyclohexylamidocarbonyl, guanidino, methyl, ethyl, methoxy,
ethoxy, hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
carboxy, carboxymethyl, amino, acetamido, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido,
aminomethyl, N-methylamino, dimethylamino, methoxyamino,
amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,
methanesulfonamido, methoxycarbonyl, fluoro, chloro, bromo, and
cyano; A is selected from the group consisting of a bond, NH,
N(CH.sub.3), CH.sub.2, CH.sub.3CH, CH.sub.2CH.sub.2, and
CH.sub.2CH.sub.2CH.sub.2; X.sup.o is selected from the group
consisting of hydrido, hydroxy, hydroxymethyl, amino, aminomethyl,
methylamino, cyano, methyl, trifluoromethyl, methoxy, methylthio,
trifluoromethoxy, fluoro, and chloro; R.sup.2 is selected from the
group consisting of phenyl, 2-thienyl, 2-furyl, 2-pyrrolyl,
2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl, and 3-pyridyl,
wherein a carbon adjacent to the carbon at the point of attachment
of said phenyl or heteroaryl ring to the 1,4-quinone ring is
optionally substituted by R.sup.9, the other carbon adjacent to the
carbon at the point of attachment is optionally substituted by
R.sup.13, a carbon adjacent to R.sup.9 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.10, a carbon adjacent to R.sup.13 and two atoms from the
carbon at the point of attachment is optionally substituted by
R.sup.12, and any carbon adjacent to both R.sup.10 and R.sup.12 is
optionally substituted by R.sup.11; Y.sup.AT is Q.sup.b-Q.sup.s;
Q.sup.s is selected from the group consisting of:
C[R.sup.37(benzoyl)(CR.sup.37R.sup.38).sub.b],
C[R.sup.37(2-pyridylcarbonyl)(CR.sup.37R.sup.38).sub.b],
C[R.sup.37(3-pyridylcarbonyl)(CR.sup.37R.sup.38).sub.b],
C[R.sup.37(4-pyridylcarbonyl)(CR.sup.37R.sup.38).sub.b],
C[R.sup.37(2-thienylcarbonyl)(CR.sup.37R.sup.38).sub.b],
C[R.sup.37(3-thienylcarbonyl)(CR.sup.37R.sup.38).sub.b]C[R.sup.37(2-thiaz-
olylcarbonyl)(CR.sup.37R.sup.38).sub.b],
C[R.sup.37(4-thiazolylcarbonyl)(C- R.sup.37R.sup.38).sub.b], and
C[R.sup.37(5-thiazolylcarbonyl)((CR.sup.37R.- sup.38).sub.b],
wherein b is an integer selected from 1 through 3, R.sup.37 and
R.sup.38 are independently selected from the group consisting of
hydrido, alkyl, and haloalkyl, with the proviso that said benzoyl
and the heteroaroyls are optionally substituted with one or more
substituents selected from the group consisting of
R.sup.16,R.sup.17,R.sup.18, and R.sup.19 with the proviso that
R.sup.17 and R.sup.18 are optionally substituted at a carbon
selected from other than the meta and para carbons relative to the
carbonyl of the benzoyl or heteroaroyl, with the further proviso
that said benzoyl or said heteroaroyl are bonded to the carbon
directly bonded to amide nitrogen of the 1-(amidocarbonymethylene)
group, and with the still further proviso that is no more than one
alkyl or one haloalkyl is bonded to a CR.sup.37R.sup.38 at the same
time; R.sup.16,R.sup.17,R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, methyl, ethyl,
amidino, guanidino, methoxy, hydroxy, amino, aminomethyl,
1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,
methylthio, ethylthio, trifluoromethylthio, methylsulfinyl,
methylsulfonyl, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, trifluoromethoxy, fluoro, chloro,
hydroxymethyl, carboxy, and cyano; Q.sup.b
(NR.sup.25)NR.sup.23R.sup.24 or N(R.sup.26)C(NR.sup.25)N(R.sup.23-
)(R.sup.24); R.sup.23,R.sup.24,R.sup.25, and R.sup.26 are
independently selected from the group consisting of hydrido,
methyl, and ethyl.
55. Compound of claim 54 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
2-aminophenyl, 3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl,
3-carboxyphenyl, 3-carboxy-5-hydroxyphenyl, 3-chlorophenyl,
4-chlorophenyl, 3,4-dichlorophenyl, 2-fluorophenyl, 3-fluorophenyl,
3,4-difluorophenyl, 3-hydroxyphenyl, 4-hydroxyphenyl,
3-methoxyaminophenyl, 3-methoxyphenyl, 4-methoxyphenyl,
3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoromethylphenyl,
2-imidazoyl, 2-pyridyl, 3-pyridyl,
5-chloro-3-trifluoromethyl-2-pyridyl, 4-pyridyl, 2-thienyl,
3-thienyl, and 3-trifluoromethyl-2-pyridyl; B is optionally
selected from the group consisting of hydrido, ethyl, 2-propenyl,
2-propynyl, propyl, isopropyl, butyl, 2-butyl, (R)-2-butyl,
(S)-2-butyl, tert-butyl, isobutyl, 1-pentyl, 3-pentyl,
2-methylbutyl, 2,2,2-trifluoroethyl, 6-amidocarbonylhexyl,
4-methyl-2-pentyl, 3-hydroxypropyl, 1-methoxy-2-propyl,
2-methoxyethyl, 2-methyl-2-butyl, 3-methyl-2-butyl,
2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl,
2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl,
3-guanidinopropyl, 4-guanidinobutyl, 3-hydroxypropyl,
4-hydroxybutyl, 6-cyanohexyl, 2-dimethylaminoethyl, 3-methylbutyl,
2-methylbutyl, (S)-2-methylbutyl, 3-aminopropyl, 2-hexyl, and
4-aminobutyl; B is optionally selected from the group consisting of
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxalan-2-yl,
2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl, azetidin-1-yl,
azetidin-2-yl, azetidin-3-yl, 1-pyrrolidinyl and 1-piperidinyl; A
is selected from the group consisting of a bond, CH.sub.2,
CH.sub.3CH, CH.sub.2CH.sub.2, and CH.sub.2CH.sub.2CH.sub.2; X.sup.o
is selected from the group consisting of hydrido, hydroxy,
hydroxymethyl, amino, aminomethyl, cyano, methyl, trifluoromethyl,
fluoro, and chloro; R.sup.2 is selected from the group consisting
of 3-amidocarbonyl-5-aminophenyl, 3-amidocarbonyl-5-aminophenyl,
3-amino-5-(N-benzylamidocarbonyl)phenyl,
3-amino-5-(N-(2-chlorobenzyl)ami- docarbonyl)phenyl,
3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-methyl-- 1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-benzylamidosulfonyl)pheny- l,
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl,
3-amino-5-(N-ethylamidocarbonyl)phenyl,
3-amino-5-(N-isopropylamidocarbon- yl)phenyl,
3-amino-5-(N-propylamidocarbonyl)phenyl,
3-amino-5-(N-isobutylamidocarbonyl)phenyl,
3-amino-5-(N-(2-butyl)amidocar- bonyl)phenyl,
3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,
3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,
3-amino-5-(N-cyclohexylamid- ocarbonyl)phenyl,
5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl,
5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl,
3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl,
3-carboxyphenyl, 3-carboxy-5-aminophenyl,
3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl,
3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl,
3-chlorophenyl, 2-chlorophenyl, 3-cyanophenyl, 5diaminophenyl,
3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,
2,5difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,
3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,
3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,
3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl,
4-methylphenyl, phenyl, 3-trifluoroacetamidophenyl,
3-trifluoromethylphenyl, 2-trifluoromethylphenyl,
5-amino-2-thienyl, 5amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl,
4pyridyl, 2-thienyl, and 3-thienyl; Y.sup.AT is Q.sup.b-Q.sup.s;
Q.sup.s is selected from the group consisting of:
[CH(benzoyl)](CH.sub.2).sub.b, [CH(2-pyridylcarbonyl)](CH.-
sub.2).sub.b, [CH(3-pyridylcarbonyl)](CH.sub.2).sub.b,
[CH(4-pyridylcarbonyl)](CH.sub.2).sub.b, [CH(2-thienyl
carbonyl)](CH.sub.2).sub.b,[CH(3-thienylcarbonyl)](CH.sub.2).sub.b,
[CH(2-thiazolylcarbonyl)](CH.sub.2).sub.b,
[CH(4-thiazolylcarbonyl)](CH.s- ub.2).sub.b, and
[CH(5-thiazolylcarbonyl)](CH.sub.2).sub.b, wherein b is an integer
selected from 1 through 3, with the proviso that said benzoyl and
said heteroaroyls are optionally substituted with one or more
substituents selected from the group consisting of
R.sup.16,R.sup.17,R.sup.18, and R.sup.19 with the proviso that
R.sup.17 and R.sup.18 are optionally substituted at a carbon
selected from other than the meta and para carbons relative to the
carbonyl of the benzoyl or the heteroaroyl, and that said benzoyl
or said heteroaroyl are bonded to the carbon directly bonded to
amide nitrogen of the 1-(amidocarbonymethylene) group; R.sup.16 and
R.sup.18 are independently selected from the group consisting of
hydrido, amidino, amino, aminomethyl, methoxy, methylamino,
hydroxy, hydroxymethyl, fluoro, chloro, and cyano; R.sup.17 and
R.sup.18 are independently selected from the group consisting of
hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy,
and cyano; Q.sup.b is N(R.sup.26)C(NR.sup.25)N(R.sup.23)(-
R.sup.24); R.sup.23,R.sup.24,R.sup.25, and R.sup.26 are
independently hydrido or methyl.
56. Compound of claim 55 or a pharmaceutically acceptable salt
thereof, wherein; B is selected from the group consisting of
3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl, 3-chlorophenyl,
4-chlorophenyl, 3,4-dichlorophenyl, 2-fluorophenyl, 4-methylphenyl,
phenyl, 2-imidazoyl, 3-pyridyl, 4-pyridyl, and
3-trifluoromethyl-2-pyridyl; B is optionally selected from the
group consisting of hydrido, ethyl, 2-propenyl, 2-propynyl, propyl,
isopropyl, butyl, 2-butyl, (R)-2-butyl, (S)-2-butyl, tert-butyl,
isobutyl, 1-pentyl, 3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl,
6-amidocarbonylhexyl, 4methyl-2-pentyl, 3-hydroxypropyl,
1-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl,
3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl,
6-hydroxyhexyl, 2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl,
3-guanidinopropyl, 4-guanidinobutyl, 3-hydroxypropyl,
4-hydroxybutyl, 6-cyanohexyl, 2-dimethylaminoethyl, 3-methylbutyl,
2-methylbutyl, (S)-2-methylbutyl, 3-aminopropyl, 2-hexyl, and
4-aminobutyl; B is optionally selected from the group consisting of
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxalan-2-yl,
2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl, azetidin-1-yl,
azetidin-2-yl, azetidin-3-yl, and 1-piperidinyl; A is selected from
the group consisting of a bond, CH.sub.2, CH.sub.2CH.sub.2 and
CH.sub.2CH.sub.2CH.sub.2; X.sup.o is selected from the group
consisting of hydrido, hydroxy, hydroxymethyl, amino, aminomethyl,
cyano, methyl, trifluoromethyl, and fluoro; R.sup.2 is selected
from the group consisting of 3-amidocarbonyl-5-aminophenyl,
3-amino-5-(N-benzylamidocarb- onyl)phenyl,
3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-(1-methyl-- 1-phenylethyl)amidocarbonyl)phenyl,
3-amino-5-(N-benzylamidosulfonyl)pheny- l,
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl,
3-amino-5-(N-ethylamidocarbonyl)phenyl, 3-amino-5-(N-isopropyl
amidocarbonyl)phenyl, 3-amino-5-(N-propylamidocarbonyl)phenyl,
3-amino-5-(N-isobutylamidocarbonyl)phenyl,
3-amino-5-(N-(2-butyl)amidocar- bonyl)phenyl,
3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,
3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,
3-amino-5-(N-cyclohexylamid- ocarbonyl)phenyl, 3-aminophenyl,
3-carboxy-5-aminophenyl, 3-chlorophenyl, 3,5-diaminophenyl,
3-dimethylaminophenyl, 3-hydroxyphenyl,
3-methanesulfonylaminophenyl, 3-methylaminophenyl, 2-methylphenyl,
3-methylphenyl, phenyl, 3-trifluoroacetamidophenyl,
3-bromo-2-thienyl, 2-thienyl, and 3-thienyl; Y.sup.AT is selected
from the group consisting of
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl,
5-guanidino-1-oxo-1-(4thia- zolyl)-2-pentyl,
5-guanidino-1-oxo-1-(5-thiazolyl)-2-pentyl,
5-guanidino-1-oxo-1-(4-amino-2-thiazolyl)-2-pentyl, and
5-guanidino-1-oxo-1-phenyl-2-pentyl.
57. A compound as recited in claim 53 where said compound is
selected from the group of the Formula: 117or a pharmaceutically
acceptable salt thereof, wherein B, A, R.sup.2, X.sup.0, and
Y.sup.AT are selected to form a compound selected from the group
consisting of; R.sup.2 is 3-aminophenyl, B is phenyl, A is
CH.sub.2CH.sub.2, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.o is chloro;
R.sup.2 is 3,5-diaminophenyl, B is phenyl, A is CH.sub.2CH.sub.2,
Y.sup.AT is 5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.o
is chloro; R.sup.2 is 3-carboxy-5-aminophenyl, B is phenyl, A is
CH.sub.2CH.sub.2, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.o is chloro;
R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl- , B is phenyl,
A is CH.sub.2CH.sub.2, Y.sup.AT is 5-guanidino-1-oxo-1-(2-t-
hiazolyl)-2-pentyl, and X.sup.o is chloro; R.sup.2 is
3,5-diaminophenyl, B is isopropyl, A is single bond, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazo- lyl)-2-pentyl, and X.sup.o is
chloro; R.sup.2 is 3-carboxy-5-aminophenyl, B is isopropyl, A is
single bond, Y.sup.AT is 5-guanidino-1-oxo-1-(2-thia-
zolyl)-2-pentyl, and X.sup.o is chloro; R.sup.2 is
3-amino-5-(N-benzylamid- ocarbonyl)phenyl, B is isopropyl, A is
single bond, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.o is chloro;
R.sup.2 is 3,5-diaminophenyl, B is cyclobutyl, A is single bond,
Y.sup.AT is 5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.o
is chloro; R.sup.2 is 3-carboxy-5-aminophenyl, B is cyclobutyl, A
is single bond, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.o is chloro;
R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
cyclobutyl, A is single bond, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazoly- l)-2-pentyl, and X.sup.o is
chloro; R.sup.2 is 3-aminophenyl, B is phenyl, A is
CH.sub.2CH.sub.2, Y.sup.AT is
S-guanidino-1-oxo-1-(2-thiazolyl)-2-pe- ntyl, and X.sup.o is
hydrido; R.sup.2 is 3,5-diaminophenyl, B is phenyl, A is
CH.sub.2CH.sub.2, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pent- yl, and X.sup.o is
hydrido; R.sup.2 is 3-carboxy-5-aminophenyl, B is phenyl, A is
CH.sub.2CH.sub.2, Y.sup.AT is 5-guanidino-1-oxo-1-(2-thiazol-
yl)-2-pentyl, and X.sup.o is hydrido; R.sup.2 is
3-amino-5-(N-benzylamidoc- arbonyl)phenyl, B is phenyl, A is
CH.sub.2CH.sub.2, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.o is hydrido;
R.sup.2 is 3,5-diaminophenyl, B is isopropyl, A is single bond,
Y.sup.AT is 5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.o
is hydrido; R.sup.2 is 3-carboxy-5-aminophenyl, B is isopropyl, A
is single bond, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.o is hydrido;
R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl,
A is single bond, Y.sup.AT is 5-guanidino-1-oxo-1-(2-thiazolyl-
)-2-pentyl, and X.sup.o is hydrido; R.sup.2 is 3,5-diaminophenyl, B
is cyclobutyl, A is single bond, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazoly- l)-2-pentyl, and X.sup.o is
hydrido; R.sup.2is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is
single bond, Y.sup.AT is 5-guanidino-1-oxo-1-(2-thiaz-
olyl)-2-pentyl, and X.sup.o is hydrido; and R.sup.2 is
3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is
single bond, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.o is
hydrido.
58. A composition for inhibiting thrombotic conditions in blood
comprising a compound of claim 21 and a pharmaceutically acceptable
carrier.
59. A method for inhibiting thrombotic conditions in blood
comprising adding to blood a therapeutically effective amount of a
composition of claim 58.
60. A method for inhibiting formation of blood platelet aggregates
in blood comprising adding to blood a therapeutically effective
amount of a composition of claim 58.
61. A method for inhibiting thrombus formation in blood comprising
adding to blood a therapeutically effective amount of a composition
of claim 58.
62. A method for treating or preventing venuous thromboembolism and
pulmonary embolism in a mammal comprising administering to the
mammal a therapeutically effective amount of a composition of claim
58.
63. A method for treating or preventing deep vein thrombosis in a
mammal comprising administering to the mammal a therapeutically
effective amount of a composition of claim 58.
64. A method for treating or preventing cardiogenic thromboembolism
in a mammal comprising administering to the mammal a
therapeutically effective amount of a composition of claim 58.
65. A method for treating or preventing thromboembolic stroke in
humans and other mammals comprising administering to the mammal a
therapeutically effective amount of a composition of claim 58.
66. A method for treating or preventing thrombosis associated with
cancer and cancer chemotherapy in humans and other mammals
comprising administering to the mammal a therapeutically effective
amount of a composition of claim 58.
67. A method for treating or preventing unstable angina in humans
and other mammals comprising administering to the mammal a
therapeutically effective amount of a composition of claim 58.
68. A method for inhibiting thrombus formation in blood comprising
adding to blood a therapeutically effective amount of a compound of
claim 21 with a therapeutically effective amount of fibrinogen
receptor antagonist.
69. The use of a compound of claim 21, or a pharmaceutically
acceptable salt thereof, in the manufacture of medicament for
inhibiting thrombus formation, treating thrombus formation, or
preventing thrombus formation in a mammal.
Description
FIELD OF THE INVENTION
[0001] This invention is in the field of anticoagulant therapy, and
specifically relates to compounds, compositions and methods for
preventing and treating thrombotic conditions such as coronary
artery and cerebrovascular disease. More particularly, the
invention relates to polycyclic aryl and heteroaryl substituted
1,4-quinone compounds that inhibit serine proteases of the
coagulation cascade.
BACKGROUND OF THE INVENTION
[0002] Physiological systems control the fluidity of blood in
mammals [Majerus, P. W. et al: Anticoagulant, Thrombolytic, and
Antiplatelet Drugs. In Hardman, J. G. and Limbird, L. E., editors:
Goodman & Gilman's The Pharmacological Basis of Therapeutics.
9th edition. New York, McGraw-Hill Book Co., 1996, pp. 1341-1343].
Blood must remain fluid within the vascular systems and yet be able
to undergo hemostasis, cessation of blood loss from a damaged
vessel, quickly. Hemostasis or clotting begins when platelets first
adhere to macromolecules in subendothelian regions of an injured
and/or damaged vessels. These platelets aggregate to form the
primary hemostatic plug and stimulate local activation of plasma
coagulation factors leading to generation of a fibrin clot that
reinforces the aggregated platelets.
[0003] Plasma coagulation factors include factors II, V, VII, VIII,
IX, X, XI, and XII; these are also called protease zymogens. These
coagulation factors or protease zymogens are activated by serine
proteases leading to coagulation in a so called "coagulation
cascade" or chain reaction [Handin, R. I.: Bleeding and Thrombosis.
In Wilson, J., et al. editors: Harrison's Principles of Internal
Medicine. 12th Edition, New York, McGraw-Hill Book Co., 1991,
p.350]. Coagulation or clotting occurs in two ways through
different pathways. An intrinsic or contact pathway leads from XII
to XIIa to XIa to IXa and to the conversion of X to Xa. Xa with
factor Va converts prothrombin (II) to thrombin (IIa) leading to
conversion of fibrinogen to fibrin. Polymerization of fibrin leads
to a fibrin clot. An extrinsic pathway is initiated by the
conversion of coagulation factor VII to VIIa by Xa. The presence of
Tissue Factor and VIIa accelerates formation of Xa in the presence
of calcium ion and phospholipids. Formation of Xa leads to
thrombin, fibrin, and a fibrin clot as described above. The
presence of one or more of these many different coagulation factors
and two distinct pathways of clotting could enable the efficacious,
selective control and better understanding of parts of the
coagulation or clotting process.
[0004] While clotting as a result of an injury to a blood vessel is
a critical physiological process for mammals such as man, clotting
can also lead to disease states. A pathological process called
thrombosis results when platelet aggregation and/or a fibrin clot
blocks (i.e., occludes) a blood vessel. Arterial thrombosis may
result in ischemic necrosis of the tissue supplied by the artery.
When the thrombosis occurs in a coronary artery, a myocardial
infarction or heart attack can result. A thrombosis occurring in a
vein may cause tissues drained by the vein to become edematous and
inflamed. Thrombosis of a deep vein may be complicated by a
pulmonary embolism. Preventing or treating clots in a blood vessel
may be therapeutically useful by inhibiting formation of blood
platelet aggregates, inhibiting formation of fibrin, inhibiting
thrombus formation, inhibiting embolus formation, and for treating
or preventing unstable angina, refractory angina, myocardial
infarction, transient ischemic attacks, atrial fibrillation,
thrombotic stroke, embolic stroke, deep vein thrombosis,
disseminated intravascular coagulation, ocular build up of fibrin,
and reocclusion or restenosis of recanalized vessels.
[0005] There have been several reports of non-peptidic and peptidic
2-pyridone compounds that act as an inhibitor of a coagulation
factor present in the coagulation cascade or clotting process. In
U.S. Pat. No. 5,668,289, Sanderson et al. describe 6-alkyl,
6-cycloalkyl, and 6-trifluoromethyl 2-pyridones unsubstituted at
the 4 and 5 positions and reported to inhibit thrombin. In PCT
Patent Application WO 97/01338, Sanderson et al. describe 6-alkyl,
6-cycloalkyl, and 6-trifluoromethyl 2-pyridones unsubstituted at
the 4 and 5 positions and reported to inhibit thrombin. In U.S.
Pat. No. 5,792,779, Sanderson et al. describe substituted
4,6-alkyl, 4,6-cycloalkyl, and 4,6-trifluoromethyl 2-pyridones
having utility as thrombin inhibitors. In PCT Patent Application WO
97/30708, Sanderson et al. describe additional substituted
4,6-alkyl, 4,6-cycloalkyl, and 4,6-trifluoromethyl 2-pyridones
having utility as thrombin inhibitors. In U.S. Pat. No. 5,869,487,
Coburn et al. describe pyrido[3,4-B]pyrazines containing a fused
6-methyl-2-pyridone functionality and having utility as thrombin
inhibitors. In PCT Patent Application WO 98/47876, Van Boeckel et
al. describe 6-alkyl-2-pyridones as anti-thrombotic compounds. In
PCT Patent Application WO 98/16547, Zhu and Scarborough describe
4,5,6-substituted-3-amino-2-pyridonylacetamides containing amide
substituents having a heteroaroyl functions and having activity
against mammalian factor Xa. In U.S. Pat. No. 5,656,645, Tamura et
al. describe 4,5,6-substituted-3-amino-2-pyridonyl-acetamides
containing amide substituents having a formyl function and having
activity against thrombin. In U.S. Pat. No. 5,658,930, Tamura et
al. again describe 4,5,6-substituted-3-amino-2-pyridonyl-acetamides
containing amide substituents having a formyl function and having
activity against thrombin. In PCT Patent Applications 96/18644,
Tamura et al. further describe
4,5,6-substituted-3-amino-2-pyridonylacetamides containing amide
substituents having a formyl function and having activity against
thrombin. In PCT Patent Application WO 98/31670, Sanderson et al.
describe additional 4-substituted 6-alkyl, 6-cycloalkyl, and
6-trifluoromethyl pyridones having utility as thrombin inhibitors.
In PCT Patent Application WO 98/17274, Coburn et al. disclose
substituted 3,4-diamino-6-methyl-2-pyridones having utility as
human thrombin inhibitors. In PCT Patent Application WO 98/42342,
Isaacs et al. describe additional 6-alkyl, cycloalkyl, and
trifluoromethyl substituted 2-pyridones reported to inhibit human
thrombin.
[0006] In contrast to the disclosures that some 2-pyridone
derivatives may function as thrombin inhibitors, 4-pyronyl
compounds, compositions thereof, their use for preventing and
treating thrombotic conditions such as coronary artery and
cerebrovascular disease, and their ability to inhibit serine
proteases of the coagulation cascade have not been previously
disclosed.
SUMMARY OF THE INVENTION
[0007] It is an object of the present invention to provide novel
compounds that are beneficial in anticoagulant therapy and that
have a general structure: 1
[0008] It is another object of the present invention to provide
methods for preventing and treating thrombotic conditions, such as
coronary artery disease, cerebrovascular disease, and other
coagulation related disorders. Such thrombotic conditions are
prevented and treated by administering to a patient in need thereof
an effective amount of compounds of Formula (I).
[0009] Various other objects and advantages of the present
invention will become apparent from the following description of
the invention.
DESCRIPTION OF THE INVENTION
[0010] The present invention relates to a class of compounds
comprising Polycyclic Aryl and Heteroaryl Substituted 1,4-quinones,
which are beneficial in anticoagulant therapy for the treatment and
prevention of a variety of thrombotic conditions including coronary
artery and cerebrovascular disease, as given in Formula (I): 2
[0011] or a pharmaceutically acceptable salt thereof, wherein;
[0012] B is formula (V): 3
[0013] wherein D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are
independently selected from the group consisting of C, N, O, S and
a covalent bond with the provisos that no more than one can be a
covalent bond, no more than one of D.sup.1, D.sup.2, J.sup.1,
J.sup.2 and K.sup.1 can be O, no more than one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 can be S, one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 must be a covalent bond when two of
D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are O and S, and no
more than four of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1
can be N with the proviso that R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36 are each independently selected to maintain
the tetravalent nature of carbon, trivalent nature of nitrogen, the
divalent nature of sulfur, and the divalent nature of oxygen;
[0014] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 can
independently be Q.sup.b;
[0015] R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.16,
R.sup.17, R.sup.18, R.sup.19, R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36 are independently selected from the group
consisting of hydrido, amidino, guanidino, dialkylsulfonium,
trialkylphosphonium, dialkylsulfoniumalkyl, carboxy,
heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl,
acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl,
aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl,
aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl,
aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl,
cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl,
cycloalkylsulfonylalkyl, heteroarylamino,
N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl,
haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl,
heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl,
cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy,
halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy,
halocycloalkenyloxyalkyl, hydroxy, amino, alkoxyamino, thio, nitro,
lower alkylamino, alkylthio, alkylthioalkyl, arylamino,
aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl,
alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl,
arylsulfonylalkyl, heteroarylsulfinylalkyl,
heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl,
haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,
alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl
amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido,
diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl,
arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl,
heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio,
alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl,
heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl,
alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy,
cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkyl
alkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl,
haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl,
aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl,
aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially
saturated heterocyclyl, heteroaryl, heteroaryloxy,
heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl,
heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido,
alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyalkyl,
carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl,
cyano, carbohaloalkoxy, phosphono, phosphonoalkyl,
diaralkoxyphosphono, and diaralkoxyphosphonoalkyl;
[0016] R.sup.32 and R.sup.33, R.sup.33 and R.sup.34, R.sup.34 and
R.sup.35, and R.sup.35 and R.sup.36 can be independently selected
to form a spacer pair wherein a spacer pair is taken together to
form a linear moiety having from 3 through 6 contiguous atoms
connecting the points of bonding of said spacer pair members to
form a ring selected from the group consisting of a cycloalkenyl
ring having 5 through 8 contiguous members, a partially saturated
heterocyclyl ring having 5 through 8 contiguous members, a
heteroaryl ring having 5 through 6 contiguous members, and an aryl
with the proviso that no more than one of the group consisting of
spacer pairs R.sup.32 and R.sup.33, R.sup.33 and R.sup.34, R.sup.34
and R.sup.35, and R.sup.35 and R.sup.36 can be used at the same
time;
[0017] R.sup.9 and R.sup.10, R.sup.10 and R.sup.11, R.sup.11 and
R.sup.12, and R.sup.12 and R.sup.13 can be independently selected
to form a spacer pair wherein a spacer pair is taken together to
form a linear moiety having from 3 through 6 contiguous atoms
connecting the points of bonding of said spacer pair members to
form a ring selected from the group consisting of a cycloalkenyl
ring having 5 through 8 contiguous members, a partially saturated
heterocyclyl ring having 5 through 8 contiguous members, a
heteroaryl ring having 5 through 6 contiguous members, and an aryl
with the proviso that no more than one of the group consisting of
spacer pairs R.sup.9 and R.sup.10, R.sup.10 and R.sup.11, R.sup.11
and R.sup.12, and R.sup.12 and R.sup.13 can be used at the same
time;
[0018] B can be formula (VI): 4
[0019] wherein D.sup.3, D.sup.4, J.sup.3, and J.sup.4 are
independently selected from the group consisting of C, N, O, and S,
no more than one of D.sup.3, D.sup.4, J.sup.3, and J.sup.4 can be
O, no more than one of D.sup.3, D.sup.4, J.sup.3, and J.sup.4 can
be S, and no more than three of D.sup.1, D.sup.2, J.sup.1, and
J.sup.2 can be N with the proviso that R.sup.32, R.sup.33,
R.sup.34, and R.sup.35 are each independently selected to maintain
the tetravalent nature of carbon, trivalent nature of nitrogen, the
divalent nature of sulfur, and the divalent nature of oxygen;
[0020] B can be selected from the group consisting of C3-C8 alkyl,
C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8
haloalkenyl wherein each member of group B may be optionally
substituted at any carbon up to and including 6 atoms from the
point of attachment of B to A with one or more of the group
consisting of R.sub.32, R.sub.33, R.sub.34, R.sub.35, and
R.sub.36;
[0021] B can be selected from the group consisting of C3-C10
cycloalkyl, C5-C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and
C4-C9 partially saturated heterocyclyl, wherein each ring carbon
may be optionally substituted with R.sub.33, a ring carbon other
than the ring carbon at the point of attachment of B to A may be
optionally substituted with oxo provided that no more than one ring
carbon is substituted by oxo at the same time, ring carbon and
nitrogen atoms adjacent to the carbon atom at the point of
attachment may be optionally substituted with R.sub.9 or R.sub.13,
a ring carbon or nitrogen atom adjacent to the R.sub.9 position and
two atoms from the point of attachment may be substituted with
R.sub.10, a ring carbon or nitrogen atom adjacent to the R.sub.13
position and two atoms from the point of attachment may be
substituted with R.sub.12, a ring carbon or nitrogen atom three
atoms from the point of attachment and adjacent to the R.sub.10
position may be substituted with R.sub.11, a ring carbon or
nitrogen atom three atoms from the point of attachment and adjacent
to the R.sub.12 position may be substituted with R.sub.33, and a
ring carbon or nitrogen atom four atoms from the point of
attachment and adjacent to the R.sub.11 and R.sub.33 positions may
be substituted with R.sub.34;
[0022] A is selected from the group consisting of single covalent
bond, (W.sup.7).sub.rr--(CH(R.sup.15)).sub.pa and
(CH(R.sup.15)).sub.pa--(W.sup- .7).sub.rr wherein rr is an integer
selected from 0 through 1, pa is an integer selected from 0 through
6, and W.sup.7 is selected from the group consisting of O, S, C(O),
C(S), C(O)S, C(S)O, C(O)N(R.sup.7), C(S)N(R.sup.7), (R.sup.7)NC(O),
(R.sup.7)NC(S), S(O), S(O).sub.2, S(O).sub.2N(R.sup.7),
(R.sup.7)NS(O).sub.2, Se(O), Se(O).sub.2, Se(O).sub.2N(R.sup.7),
(R.sup.7)NSe(O).sub.2, P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8),
P(O)(R.sup.8)N(R.sup.7), C(NR.sup.7)N(R.sup.7),
(R.sup.7)NC(NR.sup.7), and N(R.sup.7);
[0023] R.sup.7 and R.sup.8 are independently selected from the
group consisting of hydrido, hydroxy, alkyl, alkenyl, aryl,
aralkyl, aryloxy, alkoxy, alkenyloxy, alkylthio, alkylamino,
arylthio, arylamino, acyl, aroyl, heteroaroyl, aralkoxyalkyl,
heteroaralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, alkenyloxyalkyl,
alkylthioalkyl, arylthioalkyl, aralkoxyalkyl, heteroaralkoxyalkyl,
alkylsulfinylalkyl, alkylsulfonylalkyl, heteroaryl, heteroaryloxy,
heteroarylamino, heteroaralkyl, heteroaralkyloxy,
heteroaralkylamino, and heteroaryloxyalkyl;
[0024] R.sup.14, R.sup.15, R.sup.37, R.sup.38, R.sup.39, R.sup.40,
R.sup.41 and R.sup.42 are independently selected from the group
consisting of hydrido, hydroxy, halo, cyano, aryloxy, amino,
alkylamino, dialkylamino, hydroxyalkyl, aminoalkyl, acyl, aroyl,
heteroaroyl, heteroaryloxyalkyl, sulfhydryl, acylamido, alkoxy,
alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl,
aryloxyalkyl, aralkoxyalkylalkoxy, alkylsulfinylalkyl,
alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkoxythioalkyl,
alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl,
arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl,
cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl,
halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl,
haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl,
halocycloalkenyloxyalkyl, saturated heterocyclyl, partially
saturated heterocyclyl, heteroaryl, heteroarylalkyl,
heteroarylthioalkyl, heteroaralkylthioalkyl, monocarboalkoxyalkyl,
dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl,
carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl,
haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl,
arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl,
aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl,
cycloalkylsulfonyl, cycloalkylsulfinylalkyl,
cycloalkylsufonylalkyl, heteroarylsulfonylalkyl,
heteroarylsulfinyl, heteroarylsulfonyl, heteroarylsulfinylalkyl,
aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy, carboxyalkyl,
carboalkoxy, carboxamide, carboxamidoalkyl, carboaralkoxy,
trialkylsilyl, dialkoxyphosphono, diaralkoxyphosphono,
dialkoxyphosphonoalkyl, and diaralkoxyphosphonoalkyl;
[0025] R.sup.14 and R.sup.14, when bonded to different carbons, can
be taken together to form a group selected from the group
consisting of covalent bond, alkylene, haloalkylene, and a linear
moiety spacer selected to form a ring selected from the group
consisting of cycloalkyl ring having from 5 through 8 contiguous
members, cycloalkenyl ring having from 5 through 8 contiguous
members, and a heterocyclyl having from 5 through 8 contiguous
members;
[0026] R.sup.14 and R.sup.15, when bonded to different carbons, can
be taken together to form a group selected from the group
consisting of covalent bond, alkylene, haloalkylene, and a linear
moiety spacer selected to form a ring selected from the group
consisting of a cycloalkyl ring having from 5 through 8 contiguous
members, a cycloalkenyl ring having from 5 through 8 contiguous
members, and a heterocyclyl having from 5 through 8 contiguous
members;
[0027] R.sup.15 and R.sup.15, when bonded to different carbons, can
be taken together to form a group selected from the group
consisting of covalent bond, alkylene, haloalkylene, and a linear
moiety spacer selected to form a ring selected from the group
consisting of cycloalkyl ring having from 5 through 8 contiguous
members, cycloalkenyl ring having from 5 through 8 contiguous
members, and a heterocyclyl having from 5 through 8 contiguous
members;
[0028] .PSI. is selected from the group consisting of NR.sup.5, O,
C(O), C(S), S, S(O), S(O).sub.2, ON(R.sup.5), P(O)(R.sup.8), and
CR.sup.39R.sup.40;
[0029] R.sup.5 is selected from the group consisting of hydrido,
alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxy, alkoxy,
alkenyloxy, alkylthio, arylthio, aralkoxyalkyl,
heteroaralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, alkenyloxyalkyl,
alkylthioalkyl, arylthioalkyl, aralkoxyalkyl, heteroaralkoxyalkyl,
alkylsulfinylalkyl, alkylsulfonylalkyl, cycloalkyl,
cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl,
cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl,
halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl,
halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, heteroaryl,
heteroarylalkyl, monocarboalkoxyalkyl, monocarboalkoxy,
dicarboalkoxyalkyl, monocarboxamido, monocyanoalkyl, dicyanoalkyl,
carboalkoxycyanoalkyl, acyl, aroyl, heteroaroyl,
heteroaryloxyalkyl, and dialkoxyphosphonoalkyl;
[0030] R.sup.39 and R.sup.40, when bonded to the same carbon, can
be taken together to form a group selected from a group consisting
of oxo, thiono, R.sup.5--N, alkylene, haloalkylene, and a linear
moiety spacer having from 2 through 7 contiguous atoms to form a
ring selected from the group consisting of a cycloalkyl ring having
from 3 through 8 contiguous members, a cycloalkenyl ring having
from 3 through 8 contiguous members, and a heterocyclyl ring having
from 3 through 8 contiguous members;
[0031] X.sup.0 and R.sup.2 are independently selected from the
group consisting of Z.sup.0-Q, hydrido, alkyl, alkenyl, and
halo;
[0032] X.sup.0 and R.sup.2 can be independently selected from the
group consisting of amidino, guanidino, dialkylsulfonium,
trialkylphosphonium, dialkylsulfoniumalkyl, heteroarylamino, amino,
nitro, alkylamino, arylamino, aralkylamino, alkanoyl, alkenoyl,
aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl,
hydroxyhaloalkyl, cyano, and phosphono;
[0033] X.sup.0 and R.sup.5 can be taken together to form a spacer
pair wherein the spacer pair forms a linear spacer moiety having
from 2 through 5 contiguous atoms connecting the points of bonding
of said spacer pair members to form a heterocyclyl ring having from
5 through 8 contiguous members;
[0034] X.sup.0 and R.sup.39 can be taken together to form a spacer
pair wherein the spacer pair forms a linear spacer moiety having
from 2 through 5 contiguous atoms connecting the points of bonding
of said spacer pair members to form a heterocyclyl ring having from
5 through 8 contiguous members;
[0035] X.sup.0 and R.sup.40 can be taken together to form a spacer
pair wherein the spacer pair forms a linear spacer moiety having
from 2 through 5 contiguous atoms connecting the points of bonding
of said spacer pair members to form a heterocyclyl ring having from
5 through 8 contiguous members;
[0036] X.sup.0 can be independently selected to form a linear
moiety having from 2 through 5 contiguous atoms linked to the
points of bonding of both R.sup.39 and R.sup.40 to form a
heterocyclyl ring having from 5 through 8 contiguous members;
[0037] R.sup.2 and R.sup.4a, R.sup.2 and R.sup.4b, R.sup.2 and
R.sup.14, and R.sup.2 and R.sup.15 can be independently selected to
form spacer pairs wherein a spacer pair is taken together to form a
linear moiety having from 2 through 5 contiguous atoms connecting
the points of bonding of said spacer pair members to form a
heterocyclyl ring having from 5 through 8 contiguous members with
the proviso that no more than one of the group of spacer pairs
consisting of R.sup.2 and R.sup.4a, R.sup.2 and R.sup.4b, R.sup.2
and R.sup.14, and R.sup.2 and R.sup.15 can be used at the same
time;
[0038] R.sup.2 can be independently selected to form a linear
moiety having from 2 through 5 contiguous atoms linked to the
points of bonding of both R.sup.4a and R.sup.4b to form a
heterocyclyl ring having from 5 through 8 contiguous members;
[0039] Z.sup.0 is selected from the group consisting of covalent
single bond, (CR.sup.41R.sup.42).sub.q wherein q is an integer
selected from 1 through 6,
(CH(R.sup.41)).sub.g--W.sup.0--(CH(R.sup.42)).sub.p wherein g and p
are integers independently selected from 0 through 3 and W.sup.0 is
selected from the group consisting of O, S, C(O), C(S), C(O)O,
C(S)O, C(O)S, C(S)S, C(O)N(R.sup.41), (R.sup.41)NC(O),
C(S)N(R.sup.41), (R.sup.41)NC(S), OC(O)N(R.sup.41),
(R.sup.41)NC(O)O, SC(S)N(R.sup.41), (R.sup.41)NC(S)S,
SC(O)N(R.sup.41), (R.sup.41)NC(O)S, OC(S)N(R.sup.41),
(R.sup.41)NC(S)O, N(R.sup.42)C(O)N(R.sup.41),
(R.sup.41)NC(O)N(R.sup.42), N(R.sup.42)C(S)N(R.sup.41),
(R.sup.41)NC(S)N(R.sup.42), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.41), N(R.sup.41)S(O).sub.2, Se, Se(O),
Se(O).sub.2, Se(O).sub.2N(R.sup.41), N(R.sup.41)Se(O).sub.2,
P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7),
N(R.sup.41), ON(R.sup.41), and SiR.sup.28R.sup.29, and
(CH(R.sup.41)).sub.e--W.sup.2--- (CH(R.sup.42)).sub.h wherein e and
h are integers independently selected from 0 through 2 and W.sup.2
is selected from the group consisting of CR.sup.41=CR.sup.42,
CR.sup.41R.sup.42=C; vinylidene), and ethynylidene (C.ident.C;
1,2-ethynyl), with the proviso that R.sup.41 and R.sup.42 are
selected from other than halo and cyano when directly bonded to N
and Z.sup.0 is directly bonded to the quinone ring;
[0040] Q is formula (II): 5
[0041] wherein D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are
independently selected from the group consisting of C, N, O, S and
a covalent bond with the provisos that no more than one can be a
covalent bond, no more than one of D.sup.1, D.sup.2, J.sup.1,
J.sup.2 and K.sup.1 can be O, no more than one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 can be S, one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 must be a covalent bond when two of
D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are O and S, and no
more than four of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1
can be N, with the proviso that R.sup.9, R.sup.10, R.sup.11,
R.sup.12, and R.sup.13 are each independently selected to maintain
the tetravalent nature of carbon, trivalent nature of nitrogen, the
divalent nature of sulfur, and the divalent nature of oxygen;
[0042] Q can be formula (III): 6
[0043] wherein D.sup.3, D.sup.4, J.sup.3, and J.sup.4 are
independently selected from the group consisting of C, N, O, and S,
no more than one of D.sup.3, D.sup.4, J.sup.3, and J.sup.4 can be
O, no more than one of D.sup.3, D.sup.4, J.sup.3, and J.sup.4 can
be S, and no more than three of D.sup.1, D.sup.2, J.sup.1, and
J.sup.2 can be N with the proviso that R.sup.9, R.sup.10, R.sup.11,
and R.sup.12 are each independently selected to maintain the
tetravalent nature of carbon, trivalent nature of nitrogen, the
divalent nature of sulfur, and the divalent nature of oxygen;
[0044] Q can be selected from the group consisting of alkyl,
alkoxy, alkylamino, alkylthio, haloalkylthio, alkenyl, alkynyl,
saturated heterocyclyl, partially saturated heterocyclyl, acyl,
aroyl, heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl,
cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy,
haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl,
haloalkenyloxyalkyl, halocycloalkoxyalkyl, and
halocycloalkenyloxyalkyl;
[0045] K is (CR.sup.4aR.sup.4b).sub.n wherein n is an integer
selected from 1 through 4;
[0046] R.sup.4a and R.sup.4b are independently selected from the
group consisting of halo, hydrido, hydroxy, cyano, hydroxyalkyl,
alkyl, alkenyl, aryl, aralkyl, aralkoxyalkyl, aryloxyalkyl,
alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl,
aralkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl,
haloalkyl, haloalkenyl, heteroaryl, heteroarylalkyl,
heteroarylthioalkyl, heteroaralkylthioalkyl, cyanoalkyl,
alkylsulfinylalkyl, alkylsulfonylalkyl, haloalkylsulfinyl,
arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfonylalkyl,
heteroarylsulfinylalkyl, aralkylsulfinylalkyl, and
aralkylsulfonylalkyl;
[0047] R.sup.4a and R.sup.4b, when bonded to the same carbon, can
be taken together to form a group selected from the group
consisting of oxo, thiono, and a linear spacer moiety having from 2
through 7 contiguous atoms connected to form a ring selected from
the group consisting of a cycloalkyl ring having 3 through 8
contiguous members, a cycloalkenyl ring having 5 through 8
contiguous members, and a heterocyclyl ring having 5 through 8
contiguous members;
[0048] E.sup.0 is E.sup.1 when K is (CR.sup.4aR.sup.4b).sub.n,
wherein E.sup.1 is selected from the group consisting of a covalent
single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,
C(O)N(R.sup.7), (R.sup.7)NC(O), C(S)N(R.sup.7), (R.sup.7)NC(S),
OC(O)N(R.sup.7), (R.sup.7)NC(O)O, SC(S)N(R.sup.7), (R.sup.7)NC(S)S,
SC(O)N(R.sup.7), (R.sup.7)NC(O)S, OC(S)N(R.sup.7), (R.sup.7)NC(S)O,
N(R.sup.8)C(O)N(R.sup.7), (R.sup.7)NC(O)N(R.sup.8),
N(R.sup.8)C(S)N(R.sup.7), (R.sup.7)NC(S)N(R.sup.8), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.7), N(R.sup.7)S(O).sub.2,
S(O).sub.2N(R.sup.7)C(O), C(O)N(R.sup.7)S(O).sub.2, Se, Se(O),
Se(O).sub.2, Se(O).sub.2N(R.sup.7), N(R.sup.7)Se(O).sub.2,
P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7),
N(R.sup.7), ON(R.sup.7), SiR.sup.28R.sup.29,
CR.sup.4a.dbd.CR.sup.4b, ethynylidene (C.ident.C; 1,2-ethynyl), and
C.dbd.CR.sup.4aR.sup.4b;
[0049] R.sup.28 and R.sup.29 are independently selected from the
group consisting of hydrido, hydroxyalkyl, alkyl, alkenyl, alkynyl,
aryl, aralkyl, aryloxyalkyl, acyl, aroyl, aralkanoyl, heteroaroyl,
aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl,
aralkylthioalkyl, heteroaralkylthioalkyl, alkoxyalkyl,
heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl,
cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl,
cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl,
halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl,
halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl,
perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl,
heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl,
cyanoalkyl, dicyanoalkyl, carboxamidoalkyl, dicarboxamidoalkyl,
cyanocarboalkoxyalkyl, carboalkoxyalkyl, dicarboalkoxyalkyl,
cyanocycloalkyl, dicyanocycloalkyl, carboxamidocycloalkyl,
dicarboxamidocycloalkyl, carboalkoxycyanocycloalky- l,
carboalkoxycycloalkyl, dicarboalkoxycycloalkyl, formylalkyl,
acylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, aralkylsulfinyl,
cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl,
heteroarylsulfonylalkyl, heteroarylsulfinylalkyl,
aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy,
dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl and
diaralkoxyphosphonoalkyl;
[0050] R.sup.28 and R.sup.28 can be taken together to form a linear
moiety spacer having from 2 through 7 contiguous atoms and forming
a ring selected from the group consisting of a cycloalkyl ring
having from 3 through 8 contiguous members, a cycloalkenyl ring
having from 3 through 8 contiguous members, and a heterocyclyl ring
having from 3 through 8 contiguous members;
[0051] K can be (CH(R.sup.14)).sub.j-T wherein j is selected from a
integer from 0 through 3 and T is selected from the group
consisting of single covalent bond, O, S, and N(R.sup.7) with the
proviso that (CH(R.sup.14)).sub.j is bonded to the quinone
ring;
[0052] E.sup.0 is E.sup.2, when K is (CH(R.sup.14)).sub.j-T,
wherein E.sup.2 is selected from the group consisting of a covalent
single bond, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,
C(O)N(R.sup.7), (R.sup.7)NC(O), C(S)N(R.sup.7), (R.sup.7)NC(S),
(R.sup.7)NC(O)O, (R.sup.7)NC(S)S, (R.sup.7)NC(O)S, (R.sup.7)NC(S)O,
N(R.sup.8)C(O)N(R.sup.7), (R.sup.7)NC(O)N(R.sup.8),
N(R.sup.8)C(S)N(R.sup.7), (R.sup.7)NC(S)N(R.sup.8), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.7), N(R.sup.7)S(O).sub.2,
S(O).sub.2N(H)C(O), C(O)N(H)S(O).sub.2, Se(O), Se(O).sub.2,
Se(O).sub.2N(R.sup.7), N(R.sup.7)Se(O).sub.2, P(O)(R.sup.8),
N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7), and
N(R.sup.7);
[0053] K can be G-(CH(R.sup.15)).sub.k wherein k is selected from
an integer from 1 through 3 and G is selected from the group
consisting of O, S, and N(R.sup.7) with the proviso that R.sup.15
is other than hydroxy, cyano, halo, amino, alkylamino,
dialkylamino, and sulfhydryl when k is 1;
[0054] E.sup.0 is E.sup.3 when K is G-(CH(R.sup.15)).sub.k wherein
E.sup.3 is selected from the group consisting of a covalent single
bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.7),
(R.sup.7)NC(O), C(S)N(R.sup.7), (R.sup.7)NC(S), OC(O)N(R.sup.7),
(R.sup.7)NC(O)O, SC(S)N(R.sup.7), (R.sup.7)NC(S)S, SC(O)N(R.sup.7),
(R.sup.7)NC(O)S, OC(S)N(R.sup.7), (R.sup.7)NC(S)O,
N(R.sup.8)C(O)N(R.sup.7), (R.sup.7)NC(O)N(R.sup.8),
N(R.sup.8)C(S)N(R.sup.7) (R.sup.7)NC(S)N(R.sup.8), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.7), N(R.sup.7)S(O).sub.2, Se, Se(O),
Se(O).sub.2, Se(O).sub.2N(R.sup.7), N(R.sup.7)Se(O).sub.2,
P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7),
N(R.sup.7), ON(R.sup.7), SiR.sup.28R.sup.29,
CR.sup.4a.dbd.CR.sup.4b, ethynylidene (C.ident.C; 1,2-ethynyl), and
C.dbd.CR.sup.4aR.sup.4b;
[0055] Y.sup.0 is formula (IV): 7
[0056] wherein D.sup.5, D.sup.6, J.sup.5, and J.sup.6 are
independently selected from the group consisting of C, N, O, S and
a covalent bond with the provisos that no more than one can be a
covalent bond, K.sup.2 is independently selected from the group
consisting of C, and N.sup.+, no more than one of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 can be O, no more than one of D.sup.5,
D.sup.6, J.sup.5, and J.sup.6 can be S, one of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 must be a covalent bond when two of D.sup.5,
D.sup.6, J.sup.5, and J.sup.6 are O and S, no more than three of
D.sup.5, D.sup.6, J.sup.5, and J.sup.6 can be N when K.sup.2 is
N.sup.+, and no more than four of D.sup.5, D.sup.6, J.sup.5, and
J.sup.6 can be N when K.sup.2 is carbon with the provisos that
R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are each independently
selected to maintain the tetravalent nature of carbon, trivalent
nature of nitrogen, the divalent nature of sulfur, and the divalent
nature of oxygen;
[0057] R.sup.16 and R.sup.17 can be independently taken together to
form a linear moiety spacer having from 3 through 6 contiguous
atoms connected to form a ring selected from the group consisting
of a cycloalkenyl ring having from 5 through 8 contiguous members,
a partially saturated heterocyclyl ring having from 5 through 8
contiguous members, a heteroaryl having from 5 through 6 contiguous
members, and an aryl;
[0058] R.sup.18 and R.sup.19 can be independently taken together to
form a linear moiety spacer having from 3 through 6 contiguous
atoms connected to form a ring selected from the group consisting
of a cycloalkenyl ring having from 5 through 8 contiguous members,
a partially saturated heterocyclyl ring having from 5 through 8
contiguous members, a heteroaryl having from 5 through 6 contiguous
members, and an aryl;
[0059] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, .sup.+NR.sup.20R.sup.21R.sup.22, oxy, alkyl,
alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, and acylamino
wherein R.sup.20, R.sup.21, and R.sup.22 are independently selected
from the group consisting of hydrido, alkyl, hydroxy, alkoxy,
alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl with the
provisos that no more than one of R.sup.20, R.sup.21, and R.sup.22
can be hydroxy, alkoxy, alkylamino, amino, and dialkylamino and
that R.sup.20, R.sup.21, and R.sup.22 must be other than be
hydroxy, alkoxy, alkylamino, amino, and dialkylamino when K.sup.2
is N.sup.+;
[0060] R.sup.20 and R.sup.21, R.sup.20 and R.sup.22, and R.sup.21
and R.sup.22 can be independently selected to form a spacer pair
wherein a spacer pair is taken together to form a linear moiety
having from 4 through 7 contiguous atoms connecting the points of
bonding of said spacer pair members to form a heterocyclyl ring
having 5 through 8 contiguous members with the proviso that no more
than one of the group consisting of spacer pairs R.sup.20 and
R.sup.21, R.sup.20 and R.sup.22, and R.sup.21 and R.sup.22 can be
used at the same time;
[0061] Q.sup.b can be selected from the group consisting of
N(R.sup.26)SO.sub.2N(R.sup.24)(R.sup.24), N(R.sup.26)C(O)OR.sup.5,
N(R.sup.26)C(O)SR.sup.5, N(R.sup.26)C(S)OR.sup.5 and
N(R.sup.26)C(S)SR.sup.5 with the proviso that no more than one of
R.sup.23, R.sup.24, and R.sup.26 can be hydroxy, alkoxy,
alkylamino, amino, or dialkylamino when two of the group consisting
of R.sup.23, R.sup.24, and R.sup.26 are bonded to the same
atom;
[0062] Q.sup.b can be selected from the group consisting of
dialkylsulfonium, trialkylphosphonium,
C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
N(R.sup.26)C(O)N(R.sup.23)(- R.sup.24),
N(R.sup.26)C(S)N(R.sup.23)(R.sup.24), C(NR.sup.25)OR.sup.5,
C(O)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
C(S)N(R.sup.26)C(NR.sup- .25)N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R- .sup.24),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24),
C(NR.sup.25)SR.sup.5, C(O)NR.sup.23R.sup.24, and
C(O)NR.sup.23R.sup.24 with the provisos that no more than one of
R.sup.23, R.sup.24, and R.sup.26 can be hydroxy, alkoxy,
alkylamino, amino, or dialkylamino when two of the group consisting
of R.sup.23, R.sup.24, and R.sup.26 are bonded to the same atom and
that said Q.sup.b group is bonded directly to a carbon atom;
[0063] R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, alkyl, hydroxy,
alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl;
[0064] R.sup.23 and R.sup.24 can be taken together to form a linear
spacer moiety having from 4 through 7 contiguous atoms connecting
the points of bonding to form a heterocyclyl ring having 5 through
8 contiguous members;
[0065] R.sup.23 and R.sup.25, R.sup.24 and R.sup.25, R.sup.25 and
R.sup.26, R.sup.24 and R.sup.26, and R.sup.23 and R.sup.26 can be
independently selected to form a spacer pair wherein a spacer pair
is taken together from the points of bonding of selected spacer
pair members to form the group L-U-V wherein L, U, and V are
independently selected from the group consisting of O, S, C(O),
C(S), C(J.sub.H).sub.2 S(O), SO.sub.2, OP(OR.sup.31)R.sup.30,
P(O)R.sup.30, P(S)R.sup.30, C(R.sup.30)R.sup.31,
C.dbd.C(R.sup.30)R.sup.31, (O).sub.2POP(O).sub.2,
R.sup.30(O)POP(O)R.sup.30, Si(R.sup.29)R.sup.28,
Si(R.sup.29)R.sup.28Si(R- .sup.29)R.sup.28,
Si(R.sup.29)R.sup.28OSi(R.sup.29)R.sup.28,
(R.sup.28)R.sup.29COC(R.sup.28)R.sup.29,
(R.sup.28)R.sup.29CSC(R.sup.28)R- .sup.29,
C(O)C(R.sup.30).dbd.C(R.sup.31), C(S)C(R.sup.30).dbd.C(R.sup.31),
S(O)C(R.sup.30).dbd.C(R.sup.31),
SO.sub.2C(R.sup.30).dbd.C(R.sup.31),
PR.sup.30C(R.sup.30).dbd.C(R.sup.31),
P(O)R.sup.30C(R.sup.30).dbd.C(R.sup- .31),
P(S)R.sup.30C(R.sup.30).dbd.C(R.sup.31), DC(R.sup.30)(R.sup.31)D,
OP(OR.sup.31)R.sup.30, P(O)R.sup.30, P(S)R.sup.30,
Si(R.sup.28)R.sup.29 and N(R.sup.30), and a covalent bond with the
proviso that no more than any two of L, U and V are simultaneously
covalent bonds and the heterocyclyl comprised of by L, U, and V has
from 5 through 10 contiguous member;
[0066] D is selected from the group consisting of oxygen, C.dbd.O,
C.dbd.S, S(O).sub.m wherein m is an integer selected from 0 through
2;
[0067] J.sub.H is independently selected from the group consisting
of OR.sup.27, SR.sup.27 and N(R.sup.20)R.sup.21;
[0068] R.sup.27 is selected from the group consisting of hydrido,
alkyl, alkenyl, alkynyl, aralkyl, aryloxyalkyl, aralkoxyalkyl,
alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl,
heteroaralkylthioalkyl, alkoxyalkyl, heteroaryloxyalkyl,
alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl,
cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl,
cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl,
halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl,
halocycloalkoxyalkyl, halocycloalkenyloxyalkyl,
perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl,
heteroarylthioalkyl, heteroaralkylthioalkyl, arylsulfinylalkyl,
arylsulfonylalkyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl,
heteroarylsulfonylalkyl, heteroarylsulfinylalkyl,
aralkylsulfinylalkyl and aralkylsulfonylalkyl;
[0069] R.sup.30 and R.sup.31 are independently selected from
hydrido, hydroxy, thiol, aryloxy, amino, alkylamino, dialkylamino,
hydroxyalkyl, heteroaryloxyalkyl, alkoxy, alkylthio, arylthio,
alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl,
aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl,
aralkylthioalkyl, heteroaralkoxythioalkyl, alkoxyalkyl,
heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl,
cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl,
cycloalkenylalkyl, haloalkyl, haloalkenyl,
haloaralkylsulfinylalkyl, aralkylsulfonylalkyl, cyanoalkyl,
dicyanoalkyl, carboxamidoalkyl, dicarboxamidoalkyl,
cyanocarboalkoxyalkyl, carboalkoxyalkyl, dicarboalkoxyalkyl,
cyanocycloalkyl, dicyanocycloalkyl, carboxamidocycloalkyl,
dicarboxamidocycloalkyl, carboalkoxycyanocycloalky- l,
carboalkoxycycloalkyl, dicarboalkoxycycloalkyl, formylalkyl,
acylalkyl, dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl,
phosphonoalkyl, dialkoxyphosphonoalkoxy, diaralkoxyphosphonoalkoxy,
phosphonoalkoxy, dialkoxyphosphonoalkyl amino,
diaralkoxyphosphonoalkylamino, phosphonoalkylamino,
dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl, sulfonylalkyl,
alkoxysulfonylalkyl, aralkoxysulfonylalkyl, alkoxysulfonylalkoxy,
aralkoxysulfonylalkoxy, sulfonylalkoxy, alkoxysulfonylalkylamino,
aralkoxysulfonylalkylamino, and sulfonylalkylamino;
[0070] R.sup.30 and R.sup.31 can be taken to form a linear moiety
spacer group having from 2 through 7 contiguous atoms to form a
ring selected from the group consisting of a cycloalkyl ring having
from 3 through 8 contiguous members, a cycloalkenyl ring having
from 3 through 8 contiguous members, and a heterocyclyl ring having
from 3 through 8 contiguous members;
[0071] R.sup.23 and R.sup.25, R.sup.24 and R.sup.25, R.sup.25 and
R.sup.26, R.sup.24 and R.sup.26, and R.sup.23 and R.sup.26 can be
independently selected to form a spacer pair wherein a spacer pair
is taken together from the points of bonding of selected spacer
pair members to form the group L-U-V wherein L, U, and V are
independently selected from the group of 1,2-disubstituted radicals
consisting of a cycloalkyl radical, a cycloalkenyl radical wherein
cycloalkyl and cycloalkenyl radicals are substituted with one or
more groups selected from R.sup.30 and R.sup.31, an aryl radical,
an heteroaryl radical, a saturated heterocyclic radical and a
partially saturated heterocyclic radical wherein said
1,2-substitutents are independently selected from C.dbd.O, C.dbd.S,
C(R.sup.28)R.sup.32, S(O), S(O).sub.2, OP(OR.sup.31)R.sup.30,
P(O)R.sup.30, P(S)R.sup.30 and Si(R.sup.28)R.sup.29;
[0072] R.sup.23 and R.sup.25, R.sup.24 and R.sup.25, R.sup.25 and
R.sup.26, R.sup.24 and R.sup.26, and R.sup.23 and R.sup.26 can be
independently selected to form a spacer pair wherein a spacer pair
is taken together from the points of bonding of selected spacer
pair members to form the group L-U-V wherein L, U, and V are
independently selected from the group of radicals consisting of
1,2-disubstituted alkylene radicals and 1,2-disubstituted
alkenylene radical wherein said 1,2-substitutents are independently
selected from C.dbd.O, C.dbd.S, C(R.sup.28)R.sup.29, S(O),
S(O).sub.2, OP(OR.sup.31)R.sup.30, P(O)R.sup.30, P(S)R.sup.30, and
Si(R.sup.28)R.sup.29 and said alkylene and alkenylene radical are
substituted with one or more R.sup.30 or R.sup.31 substituents;
[0073] Q.sup.S is selected from the group consisting of a single
covalent bond, (CR.sup.37R.sup.38).sub.b--(W.sup.0).sub.az wherein
az is an integer selected from 0 through 1, b is an integer
selected from 1 through 4, and W.sup.0 is selected from the group
consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,
C(O)N(R.sup.14), (R.sup.14)NC(O), C(S)N(R.sup.14), (R.sup.14)NC(S),
OC(O)N(R.sup.14), SC(S)N(R.sup.14), SC(O)N(R.sup.14),
OC(S)N(R.sup.14), N(R.sup.15)C(O)N(R.sup.14),
(R.sup.14)NC(O)N(R.sup.15), N(R.sup.15)C(S)N(R.sup.14),
(R.sup.14)NC(S)N(R.sup.15), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, Se, Se(O),
Se(O).sub.2, Se(O).sub.2N(R.sup.17), N(R.sup.14)Se(O).sub.2,
P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7),
N(R.sup.14), ON(R.sup.14), and SiR.sup.28R.sup.29,
(CH(R.sup.14)).sub.c--W.sup.1--(CH(R.sup.15)).sub.d wherein c and d
are integers independently selected from 1 through 4, and W.sup.1
is selected from the group consisting of O, S, C(O), C(S), C(O)O,
C(S)O, C(O)S, C(S)S, C(O)N(R.sup.14), (R.sup.14)NC(O),
C(S)N(R.sup.14), (R.sup.14)NC(S), OC(O)N(R.sup.14),
(R.sup.14)NC(O)O, SC(S)N(R.sup.14), (R.sup.14)NC(S)S,
SC(O)N(R.sup.14), (R.sup.14)NC(O)S, OC(S)N(R.sup.14),
(R.sup.14)NC(S)O, N(R.sup.15)C(O)N(R.sup.14),
(RR.sup.14)NC(O)N(R.sup.15)- , N(R.sup.5)C(S)N(R.sup.14),
(R.sup.14)NC(S)N(R.sup.15), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, Se, Se(O),
Se(O).sub.2, Se(O).sub.2N(R.sup.14), N(R.sup.14)Se(O).sub.2,
P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7),
N(R.sup.14), ON(R.sup.14), SiR.sup.28R.sup.29, and
(CH(R.sup.14)).sub.e--W.sup.2--(CH(- R.sup.15)).sub.h wherein e and
h are integers independently selected from 0 through 2 and W.sup.2
is selected from the group consisting of CR.sup.4a.dbd.CR.sup.4b,
ethynylidene (C.ident.C; 1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b
with the provisos that R.sup.14 and R.sup.15 are selected from
other than halo and cyano when directly bonded to N and that
(CR.sup.37R.sup.38).sub.b, (CH(R.sup.14)).sub.c,
(CH(R.sup.14)).sub.e and are bonded to E.sup.0;
[0074] R.sup.37 and R.sup.37, when bonded to different carbons, can
be taken together to form a linear moiety spacer having from 1
through 7 contiguous atoms to form a ring selected from the group
consisting of a cycloalkyl ring having from 3 through 8 contiguous
members, a cycloalkenyl ring having from 3 through 8 contiguous
members, and a heterocyclyl ring having from 3 through 8 contiguous
members;
[0075] R.sup.37 and R.sup.38, when bonded to different carbons, can
be taken together to form a linear moiety spacer having from 1
through 7 contiguous atoms to form a ring selected from the group
consisting of a cycloalkyl ring having from 3 through 8 contiguous
members, a cycloalkenyl ring having from 3 through 8 contiguous
members, and a heterocyclyl ring having from 3 through 8 contiguous
members;
[0076] R.sup.38 and R.sup.38, when bonded to different carbons, can
be taken together to form a linear moiety spacer having from 1
through 7 contiguous atoms to form a ring selected from the group
consisting of a cycloalkyl ring having from 3 through 8 contiguous
members, a cycloalkenyl ring having from 3 through 8 contiguous
members, and a heterocyclyl ring having from 3 through 8 contiguous
members;
[0077] R.sup.37 and R.sup.38, when bonded to the same carbon, can
be taken together to form a group selected from a group consisting
of oxo, thiono, alkylene, haloalkylene, and a linear moiety spacer
having from 2 through 7 contiguous atoms to form a ring selected
from the group consisting of a cycloalkyl ring having from 3
through 8 contiguous members, a cycloalkenyl ring having from 3
through 8 contiguous members, and a heterocyclyl ring having from 3
through 8 contiguous members;
[0078] Y.sup.0 can be Q.sup.b-Q.sup.ss wherein Q.sup.ss is selected
from the group consisting of (CR.sup.37R.sup.38).sub.f wherein f is
an integer selected from 1 through 6,
(CH(R.sup.14)).sub.c--W.sup.1--(CH(R.sup.15)).- sub.d wherein c and
d are integers independently selected from 1 through 4, and W.sup.1
is selected from the group consisting of W.sup.1 is selected from
the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,
C(S)S, C(O)N(R.sup.14), (R.sup.14)NC(O), C(S)N(R.sup.14),
(R.sup.14)NC(S), OC(O)N(R.sup.14), (R.sup.14)NC(O)O,
SC(S)N(R.sup.14), (R.sup.14)NC(S)S, SC(O)N(R.sup.14),
(R.sup.14)NC(O)S, OC(S)N(R.sup.14), (R.sup.14)NC(S)O,
N(R.sup.15)C(O)N(R.sup.14), (R.sup.14)NC(O)N(R.sup.15),
N(R.sup.15)C(S)N(R.sup.14), (R.sup.14)NC(S)N(R.sup.15), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, Se,
Se(O), Se(O).sub.2, Se(O).sub.2N(R.sup.14), N(R.sup.14)Se(O).sub.2,
P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7),
N(R.sup.14), ON(R.sup.14), SiR.sup.28R.sup.29, and
(CH(R.sup.14)).sub.e--W--(CH(R.sup.- 15)).sub.h wherein e and h are
integers independently selected from 0 through 2 and W.sup.2 is
selected from the group consisting of CR.sup.4a.dbd.CR.sup.4b,
ethynylidene (C.ident.C; 1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b
with the provisos that R.sup.14 and R.sup.15 are selected from
other than halo and cyano when directly bonded to N and that
(CR.sup.37R.sup.38).sub.f, (CH(R.sup.15)).sub.c, and
(CH(R.sup.15)).sub.e are bonded to E.sup.0;
[0079] Y.sup.0 can be Q.sup.b-Q.sup.sss wherein Q.sup.sss is
(CH(R.sup.38)).sub.r--W.sup.3, r is an integer selected from 1
through 3, and W.sup.3 is selected from the group consisting of
1,1-cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl,
1,2-cyclohexyl, 1,3-cyclohexyl, 1,4cyclohexyl, 1,2-cyclopentyl,
1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl,
2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl,
1,3-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl,
2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl,
2,3-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl,
3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl,
1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl,
4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl,
2H-pyran-2-one4,5-yl, 4H-pyranone-2,3-yl, 2,3-tetrahydrofuranyl,
2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl,
3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,
2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,
2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and
3,5-tetrahydropyranyl with the proviso that (CH(R.sup.38)).sub.r is
bonded to E.sup.0 and Q.sup.b is bonded to lowest numbered
substituent position of each W.sup.3;
[0080] Y.sup.0 can be Q.sup.b-Q.sup.sssr wherein Q.sup.sssr is
(CH(R.sup.38)).sub.r--W.sup.4, r is an integer selected from 1
through 3, and W.sup.4 is selected from the group consisting of
1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl,
1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,
2,5-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl,
1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl,
2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,
1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl,
2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl,
1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl,
4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl,
2H-pyran-2-one-4,5-yl, 4H-pyranone-2,3-yl, 2,3-tetrahydrofuranyl,
2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl,
3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,
2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,
2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and
3,5-tetrahydropyranyl with the provisos that (CH(R.sup.38)).sub.r
is bonded to E.sup.0 and Q.sup.b is bonded to highest number
substituent position of each W.sup.4;
[0081] Y.sup.0 can be Q.sup.b-Q.sup.ssss wherein Q.sup.ssss is
(CH(R.sup.38)).sub.r--W.sup.5, r is an integer selected from 1
through 3, and W.sup.5 is selected from the group consisting of
1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl,
2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl,
3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl,
2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,
3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,
2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,
2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,
3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,
2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,
3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,
2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,
1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,
3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,
2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,
3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,
1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl,
1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,
2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,
2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,
3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,
4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,
1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,
1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,
3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,
3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,
4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,
3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,
4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl
with the proviso that Q.sup.b is bonded to lowest number
substituent position of each W.sup.5 and that (CH(R.sup.38)).sub.r
is bonded to E.sup.0;
[0082] Y.sup.0 can be Q.sup.b-Q.sup.ssssr wherein Q.sup.ssssr is
(CH(R.sup.38)).sub.r--W.sup.6, r is an integer selected from 1
through 3, and W.sup.6 is selected from the group consisting of
1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl,
2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl,
3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl,
2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,
3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,
2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,
2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,
3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,
2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,
3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,
2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,
1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,
3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,
2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,
3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,
1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl,
1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,
2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,
2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,
3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,
4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,
1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,
1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,
3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,
3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,
4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,
3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,
4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl
with the proviso that Q.sup.b is bonded to highest number
substituent position of each W.sup.6 and that (CH(R.sup.38)).sub.r
is bonded to E.sup.0.
[0083] In an embodiment of compounds of Formula I or a
pharmaceutically acceptable salt thereof,
[0084] B is formula (V): 8
[0085] wherein D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are
independently selected from the group consisting of C, N, O, S and
a covalent bond with the provisos that no more than one can be a
covalent bond, no more than one of D.sup.1, D.sup.2, J.sup.1,
J.sup.2 and K.sup.1 can be O, no more than one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 can be S, one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 must be a covalent bond when two of
D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are O and S, and no
more than four of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1
can be N with the proviso that R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36 are each independently selected to maintain
the tetravalent nature of carbon, trivalent nature of nitrogen, the
divalent nature of sulfur, and the divalent nature of oxygen;
[0086] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 can
independently be Q.sup.b;
[0087] R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.16,
R.sup.17, R.sup.18, R.sup.19, R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36 are independently selected from the group
consisting of hydrido, amidino, guanidino, dialkylsulfonium,
trialkylphosphonium, dialkylsulfoniumalkyl, carboxy,
heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl,
acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl,
aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl,
aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl,
aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl,
cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl,
cycloalkylsulfonylalkyl, heteroarylamino,
N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl,
haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl,
heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl,
cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy,
halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy,
halocycloalkenyloxyalkyl, hydroxy, amino, alkoxyamino, thio, nitro,
lower alkylamino, alkylthio, alkylthioalkyl, arylamino,
aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl,
alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl,
arylsulfonylalkyl, heteroarylsulfinylalkyl,
heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl,
haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,
alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl
amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido,
diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl,
arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl,
heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio,
alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl,
heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl,
alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy,
cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower
cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl,
haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl,
hydroxyalkyl, aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl,
aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated
heterocyclyl, partially saturated heterocyclyl, heteroaryl,
heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl,
arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy,
alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido,
carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido,
carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono,
phosphonoalkyl, diaralkoxyphosphono, and
diaralkoxyphosphonoalkyl;
[0088] R.sup.32 and R.sup.33, R.sup.33 and R.sup.34, R.sup.34 and
R.sup.35, and R.sup.35 and R.sup.36 can be independently selected
to form a spacer pair wherein a spacer pair is taken together to
form a linear moiety having from 3 through 6 contiguous atoms
connecting the points of bonding of said spacer pair members to
form a ring selected from the group consisting of a cycloalkenyl
ring having 5 through 8 contiguous members, a partially saturated
heterocyclyl ring having 5 through 8 contiguous members, a
heteroaryl ring having g through 6 contiguous members, and an aryl
with the proviso that no more than one of the group consisting of
spacer pairs R.sup.32 and R.sup.33, R.sup.33 and R.sup.34, R.sup.34
and R.sup.35, and R.sup.35 and R.sup.36 can be used at the same
time;
[0089] R.sup.9 and R.sup.10, R.sup.10 and R.sup.11, R.sup.11 and
R.sup.12, and R.sup.12 and R.sup.13 can be independently selected
to form a spacer pair wherein a spacer pair is taken together to
form a linear moiety having from 3 through 6 contiguous atoms
connecting the points of bonding of said spacer pair members to
form a ring selected from the group consisting of a cycloalkenyl
ring having 5 through 8 contiguous members, a partially saturated
heterocyclyl ring having 5 through 8 contiguous members, a
heteroaryl ring having 5 through 6 contiguous members, and an aryl
with the proviso that no more than one of the group consisting of
spacer pairs R.sup.9 and R.sup.10, R.sup.10 and R.sup.11, R.sup.11
and R.sup.12, and R.sup.12 and R.sup.13 can be used at the same
time;
[0090] B can be selected from the group consisting of C3-C8 alkyl,
C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8
haloalkenyl wherein each member of group B may be optionally
substituted at any carbon up to and including 6 atoms from the
point of attachment of B to A with one or more of the group
consisting of R.sub.32, R.sub.33, R.sub.34, R.sub.35, and
R.sub.36;
[0091] B can be selected from the group consisting of C3-C10
cycloalkyl, C5-C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and
C4-C9 partially saturated heterocyclyl, wherein each ring carbon
may be optionally substituted with R.sub.33, a ring carbon other
than the ring carbon at the point of attachment of B to A may be
optionally substituted with oxo provided that no more than one ring
carbon is substituted by oxo at the same time, ring carbon and
nitrogen atoms adjacent to the carbon atom at the point of
attachment may be optionally substituted with R.sub.9 or R.sub.13,
a ring carbon or nitrogen atom adjacent to the R.sub.9 position and
two atoms from the point of attachment may be substituted with
R.sub.10, a ring carbon or nitrogen atom adjacent to the R.sub.13
position and two atoms from the point of attachment may be
substituted with R.sub.12, a ring carbon or nitrogen atom three
atoms from the point of attachment and adjacent to the R.sub.10
position may be substituted with R.sub.11, a ring carbon or
nitrogen atom three atoms from the point of attachment and adjacent
to the R.sub.12 position may be substituted with R.sub.33, and a
ring carbon or nitrogen atom four atoms from the point of
attachment and adjacent to the R.sub.11 and R.sub.33 positions may
be substituted with R.sub.34;
[0092] A is selected from the group consisting of single covalent
bond, (W.sup.7).sub.rr--(CH(R.sup.15)).sub.pa and
(CH(R.sup.15)).sub.pa--(W.sup- .7).sub.rr wherein rr is an integer
selected from 0 through 1, pa is an integer selected from 0 through
6, and W.sup.7 is selected from the group consisting of O, S, C(O),
C(S), C(O)S, C(S)O, C(O)N(R.sup.7), C(S)N(R.sup.7), (R.sup.7)NC(O),
(R.sup.7)NC(S), S(O), S(O).sub.2, S(O).sub.2N(R.sup.7),
(R.sup.7)NS(O).sub.2, P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8),
P(O)(R.sup.8)N(R.sup.7), C(NR.sup.7)N(R.sup.7),
(R.sup.7)NC(NR.sup.7), and N(R.sup.7);
[0093] R.sup.7 and R.sup.8 are independently selected from the
group consisting of hydrido, hydroxy, alkyl, acyl, aroyl,
heteroaroyl, and alkoxyalkyl;
[0094] R.sup.14, R.sup.15, R.sup.37, and R.sup.38 are independently
selected from the group consisting of hydrido, hydroxy, halo,
cyano, hydroxyalkyl, alkoxy, alkyl, alkoxyalkyl, cycloalkyl,
cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl,
haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl,
halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl,
carboxy, carboxyalkyl, carboalkoxy, carboxamide, and
carboxamidoalkyl;
[0095] .PSI.is selected from the group consisting of NR.sup.5, O,
C(O), C(S), S, S(O), S(O).sub.2, ON(R.sup.5), P(O)(R.sup.8), and
CR.sup.39R.sup.40;
[0096] R.sup.5 is selected from the group consisting of hydrido,
alkyl, alkoxy, alkoxyalkyl, haloalkyl, acyl, aroyl, and
heteroaroyl;
[0097] R.sup.39 and R.sup.40 are independently selected from the
group consisting of hydrido, hydroxy, halo, cyano, hydroxyalkyl,
acyl, aroyl, heteroaroyl, acylamido, alkoxy, alkyl, alkoxyalkyl,
haloalkyl, haloalkoxy, haloalkoxyalkyl, alkylsulfonyl,
haloalkylsulfonyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide,
and carboxamidoalkyl;
[0098] X.sup.0 and R.sup.2 are independently selected from the
group consisting of Z.sup.0-Q, hydrido, alkyl, alkenyl, and
halo;
[0099] X.sup.0 and R.sup.2 can be independently selected from the
group consisting of amidino, guanidino, dialkylsulfonium,
trialkylphosphonium, dialkylsulfoniumalkyl, heteroarylamino, amino,
nitro, alkylamino, arylamino, aralkylamino, alkanoyl, alkenoyl,
aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl,
hydroxyhaloalkyl, cyano, and phosphono;
[0100] Z.sup.0 is selected from the group consisting of covalent
single bond, (CR.sup.41R.sup.42).sub.q wherein q is an integer
selected from 1 through 6,
(CH(R.sup.41).sub.g--W.sup.0--(CH(R.sup.42)).sub.p wherein g and p
are integers independently selected from 0 through 3 and W.sup.0 is
selected from the group consisting of O, S, C(O), C(S), C(O)O,
C(S)O, C(O)S, C(S)S, C(O)N(R.sup.41), (R.sup.41)NC(O),
C(S)N(R.sup.41), (R.sup.41)NC(S), OC(O)N(R.sup.41),
(R.sup.41)NC(O)O, SC(S)N(R.sup.41), (R.sup.41)NC(S)S,
SC(O)N(R.sup.41), (R.sup.41)NC(O)S, OC(S)N(R.sup.41),
(R.sup.41)NC(S)O, N(R.sup.42)C(O)N(R.sup.41),
(R.sup.41)NC(O)N(R.sup.42), N(R.sup.42)C(S)N(R.sup.41),
(R.sup.41)NC(S)N(R.sup.42), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.41), N(R.sup.41)S(O).sub.2, P(O)(R.sup.8),
N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7), N(R.sup.41),
ON(R.sup.41), and
(CH(R.sup.41)).sub.e--W.sup.2--(CH(R.sup.42)).sub.h wherein e and h
are integers independently selected from 0 through 2 and W.sup.2 is
selected from the group consisting of CR.sup.41.dbd.CR.sup.42,
CR.sup.41R.sup.42.dbd.C; vinylidene), and ethynylidene (C.ident.C;
1,2-ethynyl), with the proviso that R.sup.41 and R.sup.42 are
selected from other than halo and cyano when directly bonded to N
and Z.sup.0 is directly bonded to the quinone ring;
[0101] R.sup.41 and R.sup.42 are independently selected from the
group consisting of hydrido, hydroxy, halo, cyano, aryloxy,
hydroxyalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, alkoxy,
alkyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy,
alkoxyalkyl, heteroaryloxyalkyl, cycloalkyl, cycloalkylalkyl,
cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl,
haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy,
haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy,
halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, saturated
heterocyclyl, partially saturated heterocyclyl, heteroaryl,
heteroaralkyl, heteroarylthioalkyl, heteroaralkylthioalkyl,
alkylsulfonyl, haloalkylsulfonyl, arylsulfonyl, arylsulfonylalkyl,
aralkylsulfonyl, cycloalkylsulfonyl, cycloalkylsufonylalkyl,
heteroarylsulfonylalkyl, heteroarylsulfonyl, and
aralkylsulfonylalkyl;
[0102] Q is formula (II): 9
[0103] wherein D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are
independently selected from the group consisting of C, N, O, S and
a covalent bond with the provisos that no more than one can be a
covalent bond, no more than one of D.sup.1, D.sup.2, J.sup.1,
J.sup.2 and K.sup.1 can be O, no more than one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 can be S, one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 must be a covalent bond when two of
D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are O and S, and no
more than four of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1
can be N, with the proviso that R.sup.9, R.sup.10, R.sup.11,
R.sup.12, and R.sup.13 are each independently selected to maintain
the tetravalent nature of carbon, trivalent nature of nitrogen, the
divalent nature of sulfur, and the divalent nature of oxygen;
[0104] Q can be formula (III): 10
[0105] wherein D.sup.3, D.sup.4, J.sup.3, and J.sup.4 are
independently selected from the group consisting of C, N, O, and S,
no more than one of D.sup.3, D.sup.4, J.sup.3, and J.sup.4 can be
O, no more than one of D.sup.3, D.sup.4, J.sup.3, and J.sup.4 can
be S, and no more than three of D.sup.1, D.sup.2, J.sup.1, and
J.sup.2 can be N with the proviso that R.sup.9, R.sup.10, R.sup.11,
and R.sup.12 are each independently selected to maintain the
tetravalent nature of carbon, trivalent nature of nitrogen, the
divalent nature of sulfur, and the divalent nature of oxygen;
[0106] Q can be selected from the group consisting of alkyl,
alkoxy, alkylamino, alkylthio, haloalkylthio, alkenyl, alkynyl,
saturated heterocyclyl, partially saturated heterocyclyl, acyl,
aroyl, heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl,
cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy,
haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl,
haloalkenyloxyalkyl, halocycloalkoxyalkyl, and
halocycloalkenyloxyalkyl;
[0107] K is (CR.sup.4aR.sup.4b).sub.n wherein n is an integer
selected from 1 through 2;
[0108] R.sup.4a and R.sup.4b are independently selected from the
group consisting of halo, hydrido, hydroxy, cyano, hydroxyalkyl,
alkyl, alkenyl, alkoxyalkyl, haloalkyl, haloalkenyl, and
cyanoalkyl;
[0109] R.sup.4a and R.sup.4b, when bonded to the same carbon, can
be taken together to form a group selected from the group
consisting of oxo, and a linear spacer moiety having from 2 through
7 contiguous atoms connected to form a ring selected from the group
consisting of a cycloalkyl ring having 3 through 8 contiguous
members, a cycloalkenyl ring having 5 through 8 contiguous members,
and a heterocyclyl ring having 5 through 8 contiguous members;
[0110] E.sup.0 is E.sup.1, when K is (CR.sup.4aR.sup.4b).sub.n,
wherein E.sup.1 is selected from the group consisting of a covalent
single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,
C(O)N(R.sup.7), (R.sup.7)NC(O), C(S)N(R.sup.7), (R.sup.7)NC(S),
OC(O)N(R.sup.7), (R.sup.7)NC(O)O, SC(S)N(R.sup.7), (R.sup.7)NC(S)S,
SC(O)N(R.sup.7), (R.sup.7)NC(O)S, OC(S)N(R.sup.7), (R.sup.7)NC(S)O,
N(R.sup.8)C(O)N(R.sup.7), (R.sup.7)NC(O)N(R.sup.8),
N(R.sup.8)C(S)N(R.sup.7), (R.sup.7)NC(S)N(R.sup.8), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.7), N(R.sup.7)S(O).sub.2,
S(O).sub.2N(R.sup.7)C(O), C(O)N(R.sup.7)S(O).sub.2, P(O)(R.sup.8),
N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7), N(R.sup.7),
ON(R.sup.7), CR.sup.4a.dbd.CR.sup.4b- , ethynylidene (C.ident.C;
1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b;
[0111] K can be (CH(R.sup.14)).sub.j-T wherein j is selected from a
integer from 0 through 2 and T is selected from the group
consisting of single covalent bond, O, S, and N(R.sup.7) with the
proviso that (CH(R.sup.14)).sub.j is bonded to the quinone
ring;
[0112] E.sup.0 is E.sup.2, when K is (CH(R.sup.14)).sub.j-T,
wherein E.sup.2 is selected from the group consisting of a covalent
single bond, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,
C(O)N(R.sup.7), (R.sup.7)NC(O), C(S)N(R.sup.7), (R.sup.7)NC(S),
(R.sup.7)NC(O)O, (R.sup.7)NC(S)S, (R.sup.7)NC(O)S, (R.sup.7)NC(S)O,
N(R.sup.8)C(O)N(R.sup.7), (R.sup.7)NC(O)N(R.sup.8),
N(R.sup.8)C(S)N(R.sup.7), (R.sup.7)NC(S)N(R.sup.8), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.7), N(R.sup.7)S(O).sub.2,
S(O).sub.2N(H)C(O), C(O)N(H)S(O).sub.2, P(O)(R.sup.8),
N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7), and
N(R.sup.7);
[0113] K can be G-(CH(R.sup.15)).sub.k wherein k is selected from
an integer from 1 through 2 and G is selected from the group
consisting of O, S, and N(R.sup.7) with the proviso that R.sup.15
is other than hydroxy, cyano, halo, amino, alkylamino,
dialkylamino, and sulfhydryl when k is 1;
[0114] E.sup.0 is E.sup.3 when K is G-(CH(R.sup.15)).sub.k wherein
E.sup.3 is selected from the group consisting of a covalent single
bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.7),
(R.sup.7)NC(O), C(S)N(R.sup.7), (R.sup.7)NC(S), OC(O)N(R.sup.7),
(R.sup.7)NC(O)O, SC(S)N(R.sup.7), (R.sup.7)NC(S)S, SC(O)N(R.sup.7),
(R.sup.7)NC(O)S, OC(S)N(R.sup.7), (R.sup.7)NC(S)O,
N(R.sup.8)C(O)N(R.sup.7), (R.sup.7)NC(O)N(R.sup.8),
N(R.sup.8)C(S)N(R.sup.7), (R.sup.7)NC(S)N(R.sup.8), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.7), N(R.sup.7)S(O).sub.2,
P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7),
N(R.sup.7), ON(R.sup.7), CR.sup.4a.dbd.CR.sup.4b- , ethynylidene
(C.ident.C; 1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b;
[0115] Y.sup.0 is formula (IV): 11
[0116] wherein D.sup.5, D.sup.6, J.sup.5, and J.sup.6 are
independently selected from the group consisting of C, N, O, S and
a covalent bond with the provisos that no more than one can be a
covalent bond, K.sup.2 is independently selected from the group
consisting of C, and N.sup.+, no more than one of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 can be O, no more than one of D.sup.5,
D.sup.6, J.sup.5, and J.sup.6 can be S, one of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 must be a covalent bond when two of D.sup.5,
D.sup.6, J.sup.5, and J.sup.6 are O and S, no more than three of
D.sup.5, D.sup.6, J.sup.5, and J.sup.6 can be N when K.sup.2 is
N.sup.+, and no more than four of D.sup.5, D.sup.6, J.sup.5, and
J.sup.6 can be N when K.sup.2 is carbon with the provisos that
R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are each independently
selected to maintain the tetravalent nature of carbon, trivalent
nature of nitrogen, the divalent nature of sulfur, and the divalent
nature of oxygen;
[0117] R.sup.16 and R.sup.17 can be independently taken together to
form a linear moiety spacer having from 3 through 6 contiguous
atoms connected to form a ring selected from the group consisting
of a cycloalkenyl ring having from 5 through 8 contiguous members,
a partially saturated heterocyclyl ring having from 5 through 8
contiguous members, a heteroaryl having from 5 through 6 contiguous
members, and an aryl;
[0118] Q is selected from the group consisting of
NR.sup.20R.sup.21, .sup.+NR.sup..degree.R.sup.21R.sup.22, oxy,
alkyl, alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, and
acylamino wherein R.sup.20, R.sup.21, and R.sup.22 are
independently selected from the group consisting of hydrido, alkyl,
hydroxy, alkoxy, alkylamino, dialkylamino, aminoalkyl, and
hydroxyalkyl with the provisos that no more than one of R.sup.20,
R.sup.21, and R.sup.22 can be hydroxy, alkoxy, alkylamino, amino,
and dialkylamino and that R.sup.20, R.sup.21, and R.sup.22 must be
other than be hydroxy, alkoxy, alkylamino, amino, and dialkylamino
when K.sup.2 is N.sup.+;
[0119] R.sup.20 and R.sup.21, R.sup.20 and R.sup.22, and R.sup.21
and R.sup.22 can be independently selected to form a spacer pair
wherein a spacer pair is taken together to form a linear moiety
having from 4 through 7 contiguous atoms connecting the points of
bonding of said spacer pair members to form a heterocyclyl ring
having 5 through 8 contiguous members with the proviso that no more
than one of the group consisting of spacer pairs R.sup.20 and
R.sup.21, R.sup.20 and R.sup.22, and R.sup.21 and R.sup.22 can be
used at the same time;
[0120] Q.sup.b can be selected from the group consisting of
N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24), N(R.sup.26)C(O)OR.sup.5,
N(R.sup.26)C(O)SR.sup.5, N(R.sup.26)C(S)OR.sup.5 and
N(R.sup.26)C(S)SR.sup.5 with the proviso that no more than one of
R.sup.23, R.sup.24, and R.sup.26 can be hydroxy, alkoxy,
alkylamino, amino, or dialkylamino when two of the group consisting
of R.sup.23, R.sup.24, and R.sup.26 are bonded to the same
atom;
[0121] Q.sup.b can be selected from the group consisting of
dialkylsulfonium, trialkylphosphonium,
C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
N(R.sup.26)C(O)N(R.sup.23)(- R.sup.24),
N(R.sup.26)C(S)N(R.sup.23)(R.sup.24), C(NR.sup.25)OR.sup.5,
C(O)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
C(S)N(R.sup.26)C(NR.sup- .25)N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R- .sup.24),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24).
C(NR.sup.25)SR.sup.5, C(O)NR.sup.23R.sup.24, and
C(O)NR.sup.23R.sup.24 with the provisos that no more than one of
R.sup.23, R.sup.24, and R.sup.26 can be hydroxy, alkoxy,
alkylamino, amino, or dialkylamino when two of the group consisting
of R.sup.23, R.sup.24, and R.sup.26 are bonded to the same atom and
that said Q.sup.b group is bonded directly to a carbon atom;
[0122] R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, alkyl, hydroxy,
alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl;
[0123] R.sup.23 and R.sup.24 can be taken together to form a linear
spacer moiety having from 4 through 7 contiguous atoms connecting
the points of bonding to form a heterocyclyl ring having 5 through
8 contiguous members;
[0124] Q.sup.s is selected from the group consisting of a single
covalent bond, (CR.sup.37R.sup.38).sub.b--(W.sup.0).sub.az wherein
az is an integer selected from 0 through 1, b is an integer
selected from 1 through 4, and W.sup.0 is selected from the group
consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,
C(O)N(R.sup.14), (R.sup.14)NC(O), C(S)N(R.sup.14), (R.sup.14)NC(S),
OC(O)N(R.sup.14), SC(S)N(R.sup.14), SC(O)N(R.sup.14),
OC(S)N(R.sup.14), N(R.sup.15)C(O)N(R.sup.14),
(R.sup.14)NC(O)N(R.sup.14), N(R.sup.15)C(S)N(R.sup.14),
(R.sup.14)NC(S)N(R.sup.15), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, P(O)(R.sup.8),
N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7), N(R.sup.14),
ON(R.sup.14), (CH(R.sup.14)).sub.c--W.sup.1--(CH(R.sup.15)).sub.d
wherein c and d are integers independently selected from 1 through
4, and W.sup.1 is selected from the group consisting of O, S, C(O),
C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.14), (R.sup.14)NC(O),
C(S)N(R.sup.14), (R.sup.14)NC(S), OC(O)N(R.sup.14),
(R.sup.14)NC(O)O, SC(S)N(R.sup.14), (R.sup.14)NC(S)S,
SC(O)N(R.sup.14), (R.sup.14)NC(O)S, OC(S)N(R.sup.14),
(R.sup.14)NC(S)O, N(R.sup.15)C(O)N(R.sup.14),
(R.sup.14)NC(O)N(R.sup.15), N(R.sup.15)C(S)N(R.sup.14),
(R.sup.14)NC(S)N(R.sup.15), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, P(O)(R.sup.8),
N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7), N(R.sup.14),
ON(R.sup.14), and
(CH(R.sup.14)).sub.e--W.sup.2--(CH(R.sup.15)).sub.h wherein e and h
are integers independently selected from 0 through 2 and W.sup.2 is
selected from the group consisting of CR.sup.4a.dbd.CR.sup.4b,
ethynylidene (C.ident.C; 1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b
with the provisos that R.sup.14 and R.sup.15 are selected from
other than halo and cyano when directly bonded to N and that
(CR.sup.37R.sup.38).sub.b, (CH(R.sup.14)).sub.c,
(CH(R.sup.14)).sub.e and are bonded to E.sup.0;
[0125] Y.sup.0 can be Q.sup.b-Q.sup.ss wherein Q.sup.ss is selected
from the group consisting of (CR.sup.37R.sup.38).sub.f wherein f is
an integer selected from 1 through 6,
(CH(R.sup.14)).sub.c--W.sup.1--(CH(R.sup.15)).- sub.d wherein c and
dare integers independently selected from 1 through 4, and W.sup.1
is selected from the group consisting of W.sup.1 is selected from
the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,
C(S)S, C(O)N(R.sup.14), (R.sup.14)NC(O), C(S)N(R.sup.14),
(R.sup.14)NC(S), OC(O)N(R.sup.14), (R.sup.14)NC(O)O,
SC(S)N(R.sup.14), (R.sup.14)NC(S)S, SC(O)N(R.sup.14),
(R.sup.14)NC(O)S, OC(S)N(R.sup.14), (R.sup.14)NC(S)O,
N(R.sup.15)C(O)N(R.sup.14), (R.sup.14)NC(O)N(R.sup.15),
N(R.sup.15)C(S)N(R.sup.14), (R.sup.14)NC(S)N(R.sup.15), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2,
P(O)(R.sup.8), N(R.sup.7)P(O)(R.sup.8), P(O)(R.sup.8)N(R.sup.7),
N(R.sup.14), ON(R.sup.14), and
(CH(R.sup.14)).sub.e--W.sup.2--(CH(R.sup.15)).sub.h wherein e and h
are integers independently selected from 0 through 2 and W.sup.2 is
selected from the group consisting of CR.sup.4a.dbd.CR.sup.4b,
ethynylidene (C.ident.C; 1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b
with the provisos that R.sup.14 and R.sup.15 are selected from
other than halo and cyano when directly bonded to N and that
(CR.sup.37R.sup.38).sub.f, (CH(R.sup.15)).sub.c, and
(CH(R.sup.15)).sub.e are bonded to E.sup.0;
[0126] Y.sup.0 can be Q.sup.b-Q.sup.sss wherein Q.sup.sss is
(CH(R.sup.38)).sub.r--W.sup.3, r is an integer selected from 1
through 3, and W.sup.3 is selected from the group consisting of
1,1-cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl,
1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl,
1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl,
2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl,
1,3-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl,
2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl,
2,3-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl,
3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl,
1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl,
4H-2,3-pyranyl-4H-2,4-pyr- anyl, 4H-2,5-pyranyl,
2H-pyran-2-one-3,4-yl, 2H-pyran-2-one4,5-yl, 4H-pyranone-2,3-yl,
2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,
2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl,
2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl,
2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl,
3,4-tetrahydropyranyl, and 3,5-tetrahydropyranyl with the proviso
that (CH(R.sup.38)).sub.r is bonded to E.sup.0 and Q.sup.b is
bonded to lowest numbered substituent position of each W.sup.3;
[0127] Y.sup.0 can be Q.sup.b-Q.sup.sssr wherein Q.sup.sssr is
(CH(R.sup.38)).sub.r--W.sup.4, r is an integer selected from 1
through 3, and W.sup.4 is selected from the group consisting of
1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl,
1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,
2,5-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl,
1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl,
2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,
1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl,
2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl,
1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl,
4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl,
2H-pyran-2-one-4,5-yl, 4H-pyranone-2,3-yl, 2,3-tetrahydrofuranyl,
2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl,
3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,
2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,
2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and
3,5-tetrahydropyranyl with the provisos that (CH(R.sup.38)).sub.r
is bonded to E.sup.0 and Q.sup.b is bonded to highest number
substituent position of each W.sup.4;
[0128] Y.sup.0 can be Q.sup.b-Q.sup.ssss wherein Q.sup.ssss is
(CH(R.sup.38)).sub.r--W.sup.5, r is an integer selected from 1
through 3, and W.sup.5 is selected from the group consisting of
1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl,
2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl,
3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl,
2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,
3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,
2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,
2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,
3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,
2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,
3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,
2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,
1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,
3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,
2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,
3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,
1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl,
1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,
2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,
2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,
3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,
4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,
1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,
1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,
3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,
3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,
4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,
3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,
4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl
with the proviso that Q.sup.b is bonded to lowest number
substituent position of each W.sup.5 and that (CH(R.sup.38)).sub.r
is bonded to E.sup.0;
[0129] Y.sup.0 can be Q.sup.b-Q.sup.ssssr wherein Q.sup.ssssr is
(CH(R.sup.38)).sub.r--W, r is an integer selected from 1 through 3,
and W.sup.6 is selected from the group consisting of 1,4-indenyl,
1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl,
2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl,
3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl,
2,7-benzofuranyl, 3,4-benzofuranyl, 3,5-benzofuranyl,
3,6-benzofuranyl, 3,7-benzofuranyl, 2,4-benzothiophenyl,
2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7-benzothiophenyl,
3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6-benzothiophenyl,
3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl,
2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl,
1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl,
2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl, 1,3-isoindolyl,
3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl,
2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl,
2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl,
3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl,
1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl,
2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl,
2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl,
2,8-quinolinyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl,
3,7-quinolinyl, 3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl,
4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl,
1,5-isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl,
1,8-isoquinolinyl, 3,4-isoquinolinyl, 3,5-isoquinolinyl,
3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8-isoquinolinyl,
4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl,
4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl,
3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl,
4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso that Q.sup.b is
bonded to highest number substituent position of each W.sup.6 and
that (CH(R.sup.38)).sub.r is bonded to E.sup.0.
[0130] In another embodiment of compounds of Formula I or a
pharmaceutically acceptable salt thereof,
[0131] B is formula (V): 12
[0132] wherein D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are
independently selected from the group consisting of C, N, O, S and
a covalent bond with the provisos that no more than one can be a
covalent bond, no more than one of D.sup.1, D.sup.2, J.sup.1,
J.sup.2 and K.sup.1 can be O, no more than one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 can be S, one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 must be a covalent bond when two of
D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are O and S, and no
more than four of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1
can be N;
[0133] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 can
independently be Q.sup.6;
[0134] R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.16,
R.sup.17, R.sup.18, R.sup.19, R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36 are independently selected from the group
consisting of hydrido, amidino, guanidino, dialkylsulfonium,
trialkylphosphonium, dialkylsulfoniumalkyl, carboxy,
heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl,
acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl,
aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl,
aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl,
aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl,
cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl,
cycloalkylsulfonylalkyl, heteroarylamino,
N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl,
haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl,
heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl,
cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy,
halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy,
halocycloalkenyloxyalkyl, hydroxy, amino, alkoxyamino, thio, nitro,
lower alkylamino, alkylthio, alkylthioalkyl, arylamino,
aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl,
alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl,
arylsulfonylalkyl, heteroarylsulfinylalkyl,
heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl,
haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,
alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl
amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido,
diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl,
arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl,
heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio,
alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl,
heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl,
alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy,
cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower
cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl,
haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl,
hydroxyalkyl, aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl,
aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated
heterocyclyl, partially saturated heterocyclyl, heteroaryl,
heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl,
arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy,
alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido,
carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido,
carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono,
phosphonoalkyl, diaralkoxyphosphono, and
diaralkoxyphosphonoalkyl;
[0135] B can be selected from the group consisting of C3-C8 alkyl,
C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8
haloalkenyl wherein each member of group B may be optionally
substituted at any carbon up to and including 6 atoms from the
point of attachment of B to A with one or more of the group
consisting of R.sub.32, R.sub.33, R.sub.34, R.sub.35, and
R.sub.36;
[0136] B can be selected from the group consisting of C3-C10
cycloalkyl, C5-C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and
C4-C9 partially saturated heterocyclyl, wherein each ring carbon
may be optionally substituted with R.sub.33, a ring carbon other
than the ring carbon at the point of attachment of B to A may be
optionally substituted with oxo provided that no more than one ring
carbon is substituted by oxo at the same time, ring carbon and
nitrogen atoms adjacent to the carbon atom at the point of
attachment may be optionally substituted with R.sub.9 or R.sub.13,
a ring carbon or nitrogen atom adjacent to the R.sub.9 position and
two atoms from the point of attachment may be substituted with
R.sub.10, a ring carbon or nitrogen atom adjacent to the R.sub.13
position and two atoms from the point of attachment may be
substituted with R.sub.12, a ring carbon or nitrogen atom three
atoms from the point of attachment and adjacent to the R.sub.10
position may be substituted with R.sub.11, a ring carbon or
nitrogen atom three atoms from the point of attachment and adjacent
to the R.sub.12 position may be substituted with R.sub.33, and a
ring carbon or nitrogen atom four atoms from the point of
attachment and adjacent to the R.sub.11 and R.sub.33 positions may
be substituted with R.sub.34;
[0137] A is selected from the group consisting of single covalent
bond, (W.sup.7).sub.rr--(CH(R.sup.15)).sub.pa and
(CH(R.sup.15)).sub.pa--(W.sup- .7).sub.rr wherein rr is an integer
selected from 0 through 1, pa is an integer selected from 0 through
6, and W.sup.7 is selected from the group consisting of O, S, C(O),
C(S), C(O)S, C(S)O, C(O)N(R.sup.7), C(S)N(R.sup.7), (R.sup.7)NC(O),
(R.sup.7)NC(S), S(O), S(O).sub.2, S(O).sub.2N(R.sup.7),
(R.sup.7)NS(O).sub.2, C(NR.sup.7)N(R.sup.7), (R.sup.7)NC(NR.sup.7),
and N(R.sup.7);
[0138] R.sup.7 and R.sup.8 are independently selected from the
group consisting of hydrido, hydroxy, alkyl, and alkoxyalkyl;
[0139] R.sup.14, R.sup.15, R.sup.37, and R.sup.38 are independently
selected from the group consisting of hydrido, hydroxy, halo,
alkyl, alkoxyalkyl, haloalkyl, haloalkoxy, and haloalkoxyalkyl;
[0140] .PSI. is selected from the group consisting of NR.sup.5, O,
C(O), C(S), S, S(O), S(O).sub.2, and CR.sup.39R.sup.40;
[0141] R.sup.5 is selected from the group consisting of hydrido,
alkyl, and alkoxy;
[0142] R.sup.39 and R.sup.40 are independently selected from the
group consisting of hydrido, hydroxy, halo, hydroxyalkyl, alkyl,
alkoxyalkyl, haloalkyl, haloalkoxy, and haloalkoxyalkyl;
[0143] X.sup.0 and R.sup.2 are independently selected from the
group consisting of Z.sup.0-Q, hydrido, alkyl, alkenyl, and
halo;
[0144] X.sup.0 and R.sup.2 can be independently selected from the
group consisting of amidino, guanidino, dialkylsulfonium,
trialkylphosphonium, dialkylsulfoniumalkyl, heteroarylamino, amino,
nitro, alkylamino, arylamino, aralkylamino, alkanoyl, alkenoyl,
aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl,
hydroxyhaloalkyl, cyano, and phosphono; Z.sup.0 is selected from
the group consisting of covalent single bond,
(CR.sup.41R.sup.42).sub.q wherein q is an integer selected from 1
through 2, (CH(R.sup.41)).sub.g--W.sup.0--(CH(R.sup.42)).sub.p
wherein g and p are integers independently selected from 0 through
2 and W.sup.0 is selected from the group consisting of O, S, C(O),
C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.41), (R.sup.41)NC(O),
C(S)N(R.sup.41), (R.sup.41)NC(S), OC(O)N(R.sup.41),
(R.sup.41)NC(O)O, SC(S)N(R.sup.41), (R.sup.41)NC(S)S,
SC(O)N(R.sup.41), (R.sup.41)NC(O)S, OC(S)N(R.sup.41),
(R.sup.41)NC(S)O, N(R.sup.42)C(O)N(R.sup.41),
(R.sup.41)NC(O)N(R.sup.42), N(R.sup.42)C(S)N(R.sup.41),
(R.sup.41)NC(S)N(R.sup.42), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.41), N(R.sup.41)S(O).sub.2, N(R.sup.41),
ON(R.sup.41), and
(CH(R.sup.41)).sub.e--W.sup.2--(CH(R.sup.42)).sub.h wherein e and h
are integers independently selected from 0 through 2 and W.sup.2 is
selected from the group consisting of CR.sup.41.dbd.CR.sup.42,
CR.sup.41R.sup.42.dbd.C; vinylidene), and ethynylidene (C.ident.C;
1,2-ethynyl), with the proviso that R.sup.41 and R.sup.42 are
selected from other than halo and cyano when directly bonded to N
and Z.sup.0 is directly bonded to the quinone ring;
[0145] R.sup.41 and R.sup.42 are independently selected from the
group consisting of hydrido, hydroxy, halo, cyano, aryloxy,
hydroxyalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, alkoxy,
alkyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy,
alkoxyalkyl, heteroaryloxyalkyl, cycloalkyl, cycloalkylalkyl,
cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl,
haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy,
haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy,
halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, saturated
heterocyclyl, partially saturated heterocyclyl, heteroaryl, and
heteroaralkyl;
[0146] Q is formula (II): 13
[0147] wherein D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are
independently selected from the group consisting of C, N, O, S and
a covalent bond with the provisos that no more than one can be a
covalent bond, no more than one of D.sup.1, D.sup.2, J.sup.1,
J.sup.2 and K.sup.1 can be O, no more than one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 can be S, one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 must be a covalent bond when two of
D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are O and S, and no
more than four of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1
can be N, with the proviso that R.sup.9, R.sup.10, R.sup.11,
R.sup.12, and R.sup.13 are each independently selected to maintain
the tetravalent nature of carbon, trivalent nature of nitrogen, the
divalent nature of sulfur, and the divalent nature of oxygen;
[0148] Q can be selected from the group consisting of alkyl,
alkoxy, alkylamino, alkylthio, haloalkylthio, saturated
heterocyclyl, alkyl, partially saturated heterocyclyl, acyl, aroyl,
heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl,
cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy,
haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl,
haloalkenyloxyalkyl, halocycloalkoxyalkyl, and
halocycloalkenyloxyalkyl;
[0149] K is (CR.sup.4aR.sup.4b)n wherein n is the integer 1;
[0150] R.sup.4a and R.sup.4b are independently selected from the
group consisting of halo, hydrido, hydroxy, hydroxyalkyl, alkyl,
alkoxyalkyl, and haloalkyl;
[0151] E.sup.0 is E.sup.1, when K is (CR.sup.4aR.sup.4b).sub.n,
wherein E.sup.1 is selected from the group consisting of a covalent
single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,
C(O)N(R.sup.7), (R.sup.7)NC(O), C(S)N(R.sup.7), (R.sup.7)NC(S),
OC(O)N(R.sup.7), (R.sup.7)NC(O)O, SC(S)N(R.sup.7), (R.sup.7)NC(S)S,
SC(O)N(R.sup.7), (R.sup.7)NC(O)S, OC(S)N(R.sup.7), (R.sup.7)NC(S)O,
N(R.sup.8)C(O)N(R.sup.7), (R.sup.7)NC(O)N(R.sup.8),
N(R.sup.8)C(S)N(R.sup.7), (R.sup.7)NC(S)N(R.sup.8), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.7), N(R.sup.7)S(O).sub.2,
S(O).sub.2N(R.sup.7)C(O), C(O)N(R.sup.7)S(O).sub.2, N(R.sup.7),
ON(R.sup.7), CR.sup.4a.dbd.CR.sup.4b, ethynylidene (C.ident.C;
1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b;
[0152] K can be (CH(R.sup.14)).sub.j-T wherein j is selected from a
integer from 0 through 1 and T is selected from the group
consisting of single covalent bond, O, S, and N(R.sup.7) with the
proviso that (CH(R.sup.14)).sub.j is bonded to the quinone
ring;
[0153] E.sup.0 is E.sup.2, when K is (CH(R.sup.14)).sub.j-T,
wherein E.sup.2 is selected from the group consisting of a covalent
single bond, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,
C(O)N(R.sup.7), (R.sup.7)NC(O), C(S)N(R.sup.7), (R.sup.7)NC(S),
(R.sup.7)NC(O)O, (R.sup.7)NC(S)S, (R.sup.7)NC(O)S, (R.sup.7)NC(S)O,
N(R.sup.8)C(O)N(R.sup.7), (R.sup.7)NC(O)N(R.sup.8),
N(R.sup.8)C(S)N(R.sup.7), (R.sup.7)NC(S)N(R.sup.8), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.7), N(R.sup.7)S(O).sub.2,
S(O).sub.2N(H)C(O), C(O)N(H)S(O).sub.2, and N(R.sup.7);
[0154] K can be G-(CH(R.sup.15)).sub.k wherein k is the integer 1
and G is selected from the group consisting of O, S, and
N(R.sup.7);
[0155] E.sup.0 is E.sup.3 when K is G-(CH(R.sup.15)).sub.k wherein
E.sup.3 is selected from the group consisting of a covalent single
bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R.sup.7),
(R.sup.7)NC(O), C(S)N(R.sup.7), (R.sup.7)NC(S), OC(O)N(R.sup.7),
(R.sup.7)NC(O)O, SC(S)N(R.sup.7), (R.sup.7)NC(S)S, SC(O)N(R.sup.7),
(R.sup.7)NC(O)S, OC(S)N(R.sup.7), (R.sup.7)NC(S)O,
N(R.sup.8)C(O)N(R.sup.7), (R.sup.7)NC(O)N(R.sup.8),
N(R.sup.8)C(S)N(R.sup.7), (R.sup.7)NC(S)N(R.sup.8), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.7), N(R.sup.7)S(O).sub.2, N(R.sup.7),
ON(R.sup.7), CR.sup.4a.dbd.CR.sup.4b, ethynylidene (C.ident.C;
1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b;
[0156] Y.sup.0 is formula (IV): 14
[0157] wherein D.sup.5, D.sup.6, J.sup.5, and J.sup.6 are
independently selected from the group consisting of C, N, O, S and
a covalent bond with the provisos that no more than one can be a
covalent bond, K.sup.2 is independently selected from the group
consisting of C, and N.sup.+, no more than one of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 can be O, no more than one of D.sup.5,
D.sup.6, J.sup.5, and J.sup.6 can be S, one of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 must be a covalent bond when two of D.sup.5,
D.sup.6, J.sup.5, and J.sup.6 are O and S, no more than three of
D.sup.5, D.sup.6, J.sup.5, and J.sup.6 can be N when K.sup.2 is
N.sup.+, and no more than four of D.sup.5, D.sup.6, J.sup.5, and
J.sup.6 can be N when K.sup.2 is carbon with the provisos that
R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are each independently
selected to maintain the tetravalent nature of carbon, trivalent
nature of nitrogen, the divalent nature of sulfur, and the divalent
nature of oxygen;
[0158] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, .sup.+NR.sup.20R.sup.21R.sup.22, oxy, alkyl,
alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, and acylamino
wherein R.sup.20, R.sup.21, and R.sup.22 are independently selected
from the group consisting of hydrido, alkyl, hydroxy, alkoxy,
alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl with the
provisos that no more than one of R.sup.20, R.sup.21, and R.sup.22
can be hydroxy, alkoxy, alkylamino, amino, and dialkylamino and
that R.sup.20, R.sup.21, and R.sup.22 must be other than be
hydroxy, alkoxy, alkylamino, amino, and dialkylamino when K.sup.2
is N.sup.+;
[0159] Q.sup.b can be selected from the group consisting of
N(R.sup.26)SO.sub.2(R.sup.23)(R.sup.24), N(R.sup.26)C(O)OR.sup.5,
N(R.sup.26)C(O)SR.sup.5, N(R.sup.26)C(S)OR.sup.5 and
N(R.sup.26)C(S)SR.sup.5 with the proviso that no more than one of
R.sup.23, R.sup.24, and R.sup.24 can be hydroxy, alkoxy,
alkylamino, amino, or dialkylamino when two of the group consisting
of R.sup.23, R.sup.24, and R.sup.26 are bonded to the same
atom;
[0160] Q.sup.b can be selected from the group consisting of
dialkylsulfonium, trialkylphosphonium,
C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
N(R.sup.26)C(O)N(R.sup.23)(- R.sup.24),
N(R.sup.26)C(S)N(R.sup.23)(R.sup.24), C(NR.sup.25)OR.sup.5,
C(O)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
C(S)N(R.sup.26)C(NR.sup- .25)N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R- .sup.24),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24),
C(NR.sup.25)SR.sup.5, C(O)NR.sup.23R.sup.24, and
C(O)NR.sup.23R.sup.24 with the provisos that no more than one of
R.sup.23, R.sup.24, and R.sup.26 can be hydroxy, alkoxy,
alkylamino, amino, or dialkylamino when two of the group consisting
of R.sup.23, R.sup.24, and R.sup.26 are bonded to the same atom and
that said Q.sup.b group is bonded directly to a carbon atom;
[0161] R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, alkyl, hydroxy,
alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl;
[0162] Q.sup.s is selected from the group consisting of a single
covalent bond, (CR.sup.37R.sup.38).sub.b--(W.sup.0).sub.az wherein
az is an integer selected from 0 through 1, b is an integer
selected from 1 through 2, and W.sup.0 is selected from the group
consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,
C(O)N(R.sup.14), (R.sup.14)NC(O), C(S)N(R.sup.14), (R.sup.14)NC(S),
OC(O)N(R.sup.14), SC(S)N(R.sup.14), SC(O)N(R.sup.14),
OC(S)N(R.sup.14), N(R.sup.15)C(O)N(R.sup.14),
(R.sup.14)NC(O)N(R.sup.15) N(R.sup.15)C(S)N(R.sup.14),
(R.sup.14)NC(S)N(R.sup.15), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, N(R.sup.14),
ON(R.sup.14), and
(CH(R.sup.14)).sub.c--W.sup.1--(CH(R.sup.15)).sub.d wherein c and d
are integers independently selected from 1 through 2, and W.sup.1
is selected from the group consisting of O, S, C(O), C(S), C(O)O,
C(S)O, C(O)S, C(S)S, C()N(R.sup.14), (R.sup.14)NC(O),
C(S)N(R.sup.14), (R.sup.14)NC(S), OC(O)N(R.sup.14),
(R.sup.14)NC(O)O, SC(S)N(R.sup.14), (R.sup.14)NC(S)S,
SC(O)N(R.sup.14), (R.sup.14)NC(O)S, OC(S)N(R.sup.14),
(R.sup.14)NC(S)O, N(R.sup.15)C(O)N(R.sup.14),
(R.sup.14)NC(O)N(R.sup.15), N(R.sup.15)C(S)N(R.sup.14),
(R.sup.14)NC(S)N(R.sup.15), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, N(R.sup.14),
ON(R.sup.14), and
(CH(R.sup.14)).sub.e--W.sup.2--(CH(R.sup.15)).sub.h wherein e and h
are integers independently selected from 0 through 2 and W.sup.2 is
selected from the group consisting of CR.sup.4a.dbd.CR.sup.4b,
ethynylidene (C.ident.C; 1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b
with the provisos that R.sup.14 and R.sup.15 are selected from
other than halo and cyano when directly bonded to N and that
(CR.sup.37R.sup.38).sub.b, (CH(R.sup.14)).sub.c,
(CH(R.sup.14)).sub.e and are bonded to E.sup.0;
[0163] Y.sup.0 can be Q.sup.b-Q.sup.ss wherein Q.sup.ss is selected
from the group consisting of (CR.sup.37R.sup.38).sub.f wherein f is
an integer selected from 1 through 4,
(CH(R.sup.14)).sub.c--W.sup.1--(CH(R.sup.15)).- sub.d wherein c and
d are integers independently selected from 1 through 2, and W.sup.1
is selected from the group consisting of W.sup.1 is selected from
the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,
C(S)S, C(O)N(R.sup.14), (R.sup.14)NC(O), C(S)N(R.sup.14),
(R.sup.14)NC(S), OC(O)N(R.sup.14), (R.sup.14)NC(O)O,
SC(S)N(R.sup.14), (R.sup.14)NC(S)S, SC(O)N(R.sup.14),
(R.sup.14)NC(O)S, OC(S)N(R.sup.14), (R.sup.14)NC(S)O,
N(R.sup.15)C(O)N(R.sup.14), (R.sup.14)NC(O)N(R.sup.15),
N(R.sup.15)C(S)N(R.sup.14), (R.sup.14)NC(S)N(R.sup.15), S(O),
S(O).sub.2, S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2,
N(R.sup.14), ON(R.sup.14), and
(CH(R.sup.14)).sub.e--W.sup.2--(CH(R.sup.15)).sub.h wherein e and h
are integers independently selected from 0 through 2 and W.sup.2 is
selected from the group consisting of CR.sup.4a.dbd.CR.sup.4b,
ethynylidene (C.ident.C; 1,2-ethynyl), and C.dbd.CR.sup.4aR.sup.4b
with the provisos that R.sup.14 and R.sup.15 are selected from
other than halo when directly bonded to N and that
(CR.sup.37R.sup.38).sub.f, (CH(R.sup.15)).sub.c, and
(CH(R.sup.15)).sub.e are bonded to E.sup.0;
[0164] Y.sup.0 can be Q.sup.b-Q.sup.sss wherein Q.sup.sss is
(CH(R.sup.38)).sub.r--W.sup.3, r is an integer selected from 1
through 2, and W.sup.3 is selected from the group consisting of
1,1-cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl,
1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl,
1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl,
2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl,
1,3-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl,
2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl,
2,3-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl,
3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl,
1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl,
4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl,
2H-pyran-2-one4,5-yl, 4H-pyranone-2,3-yl, 2,3-tetrahydrofuranyl,
2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl,
3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,
2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,
2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and
3,5-tetrahydropyranyl with the proviso that (CH(R.sup.38)).sub.r is
bonded to E.sup.0 and Q.sup.b is bonded to lowest numbered
substituent position of each W.sup.3;
[0165] Y.sup.0 can be Q.sup.b-Q.sup.sssr wherein Q.sup.sssr is
(CH(R.sup.38)).sub.r--W.sup.4, r is an integer selected from 1
through 2, and W.sup.4 is selected from the group consisting of
1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl,
1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,
2,5-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl,
1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl,
2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,
1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl,
2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl,
1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl,
4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl,
2H-pyran-2-one4,5-yl, 4H-pyranone-2,3-yl, 2,3-tetrahydrofuranyl,
2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl,
3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,
2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,
2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and
3,5-tetrahydropyranyl with the provisos that (CH(R.sup.38)).sub.r
is bonded to E.sup.0 and Q.sup.b is bonded to highest number
substituent position of each W.sup.4;
[0166] Y.sup.0 can be Q.sup.b-Q.sup.ssss wherein Q.sup.ssss is
(CH(R.sup.38)).sub.r--W.sup.5, r is an integer selected from 1
through 2, and W.sup.5 is selected from the group consisting of
1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl,
2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl,
3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl,
2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,
3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,
2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,
2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,
3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,
2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,
3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,
2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,
1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,
3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,
2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,
3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,
1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl,
1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,
2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,
2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,
3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,
4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,
1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,
1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,
3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,
3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,
4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,
3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,
4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl
with the proviso that Q.sup.b is bonded to lowest number
substituent position of each W.sup.5 and that (CH(R.sup.38)).sub.r
is bonded to E.sup.0;
[0167] Y.sup.0 can be Q.sup.b-Q.sup.ssssr wherein Q.sup.ssssr is
(CH(R.sup.38)).sub.r--W.sup.6, r is an integer selected from 1
through 2, and W.sup.6 is selected from the group consisting of
1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl,
2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl,
3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl,
2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,
3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,
2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,
2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,
3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,
2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,
3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,
2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,
1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,
3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,
2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,
3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,
1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl,
1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,
2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,
2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,
3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,
4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,
1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,
1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,
3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,
3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,
4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,
3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,
4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl
with the proviso that Q.sup.b is bonded to highest number
substituent position of each W.sup.6 and that (CH(R.sup.38)).sub.r
is bonded to E.sup.0.
[0168] In a preferred embodiment of compounds of Formula I or a
pharmaceutically acceptable salt thereof,
[0169] B is formula (V): 15
[0170] wherein D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are
independently selected from the group consisting of C, N, O, S and
a covalent bond with the provisos that no more than one can be a
covalent bond, no more than one of D.sup.1, D.sup.2, J.sup.1,
J.sup.2 and K.sup.1 can be O, no more than one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 can be S, one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 must be a covalent bond when two of
D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are O and S, and no
more than four of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1
can be N;
[0171] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 can
independently be Q.sup.b;
[0172] R.sup.9, R.sup.10,R.sup.11, R.sup.12, R.sup.32, R.sup.33,
R.sup.34, R.sup.35, and R.sup.36 are independently selected from
the group consisting of hydrido, amidino, guanidino,
dialkylsulfonium, carboxy, haloalkylthio, alkanoyloxy, alkoxy,
alkoxyalkyl, haloalkoxylalkyl, hydroxy, amino, alkoxyamino, thio,
nitro, lower alkylamino, alkylthio, alkylthioalkyl, alkylsulfinyl,
alkylsulfinylalkyl, alkylsulfonyl, alkylsulfonylalkyl,
haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,
alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl
amidosulfonyl, alkanoyl, alkenoyl, haloalkanoyl, alkyl, alkenyl,
alkenyloxy, alkenyloxyalky, halo, haloalkyl, haloalkenyl,
haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl,
haloalkoxyalkyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido,
alkylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl,
carboxamido, carboxamidoalkyl, and cyano;
[0173] B can be selected from the group consisting of C3-C8 alkyl,
C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8
haloalkenyl wherein each member of group B may be optionally
substituted at any carbon up to and including 6 atoms from the
point of attachment of B to A with one or more of the group
consisting of R.sub.32, R.sub.33, R.sub.34, R.sub.35, and
R.sub.36;
[0174] B can be selected from the group consisting of C3-C10
cycloalkyl, C5-C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and
C4-C9 partially saturated heterocyclyl, wherein each ring carbon
may be optionally substituted with R.sub.33, a ring carbon other
than the ring carbon at the point of attachment of B to A may be
optionally substituted with oxo provided that no more than one ring
carbon is substituted by oxo at the same time, ring carbon and
nitrogen atoms adjacent to the carbon atom at the point of
attachment may be optionally substituted with R.sub.9 or R.sub.13,
a ring carbon or nitrogen atom adjacent to the R.sub.9 position and
two atoms from the point of attachment may be substituted with
R.sub.10, a ring carbon or nitrogen atom adjacent to the R.sub.13
position and two atoms from the point of attachment may be
substituted with R.sub.12, a ring carbon or nitrogen atom three
atoms from the point of attachment and adjacent to the R.sub.10
position may be substituted with R.sub.11, a ring carbon or
nitrogen atom three atoms from the point of attachment and adjacent
to the R.sub.12 position may be substituted with R.sub.33, and a
ring carbon or nitrogen atom four atoms from the point of
attachment and adjacent to the R.sub.11 and R.sub.33 positions may
be substituted with R.sub.34;
[0175] A is selected from the group consisting of single covalent
bond, (W.sup.7).sub.rr--(CH(R.sup.15)).sub.pa and
(CH(R.sup.15)).sub.pa--(W.sup- .7).sub.rr wherein rr is an integer
selected from 0 through 1, pa is an integer selected from 0 through
6, and W.sup.7 is selected from the group consisting of O, S, C(O),
C(S), C(O)S, C(S)O, C(O)N(R.sup.7), C(S)N(R.sup.7), (R.sup.7)NC(O),
(R.sup.7)NC(S), S(O), S(O).sub.2, S(O).sub.2N(R.sup.7),
(R.sup.7)NS(O).sub.2, C(NR.sup.7)N(R.sup.7), (R.sup.7)NC(NR.sup.7),
and N(R.sup.7);
[0176] R.sup.7 and R.sup.8 are independently selected from the
group consisting of hydrido, hydroxy, alkyl, and alkoxyalkyl;
[0177] R.sup.15 is selected from the group consisting of hydrido,
hydroxy, halo, alkyl, and haloalkyl;
[0178] .PSI. is NH;
[0179] X.sup.0 is hydrido;
[0180] R.sup.2 is selected from the group consisting of Z.sup.0-Q,
hydrido, alkyl, alkenyl, and halo;
[0181] Z.sup.0 is a covalent single bond;
[0182] Q is formula (II): 16
[0183] wherein D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are
independently selected from the group consisting of C, N, O, S and
a covalent bond with the provisos that no more than one can be a
covalent bond, no more than one of D.sup.1, D.sup.2, J.sup.1,
J.sup.2 and K.sup.1 can be O, no more than one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 can be S, one of D.sup.1, D.sup.2,
J.sup.1, J.sup.2 and K.sup.1 must be a covalent bond when two of
D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1 are O and S, and no
more than four of D.sup.1, D.sup.2, J.sup.1, J.sup.2 and K.sup.1
can be N, with the proviso that R.sup.9, R.sup.10, R.sup.11,
R.sup.12, and R.sup.13 are each independently selected to maintain
the tetravalent nature of carbon, trivalent nature of nitrogen, the
divalent nature of sulfur, and the divalent nature of oxygen;
[0184] K is CR.sup.4aR.sup.4b;
[0185] R.sup.4a and R.sup.4b are independently selected from the
group consisting of halo, hydrido, hydroxy, alkyl, and
haloalkyl;
[0186] E.sup.0 is E.sup.1, when K is CR.sup.4aR.sup.4b, wherein
E.sup.1 is selected from the group consisting of a covalent single
bond, (O)N(H), (H)NC(O), C(S)N(H), (H)NC(S), S(O).sub.2N(H),
N(H)S(O).sub.2, S(O).sub.2N(H)C(O), and C(O)N(H)S(O).sub.2;
[0187] K can be (CH(R.sup.14)).sub.j-T wherein j is selected from
an integer from 0 through 1 and T is selected from the group
consisting of single covalent bond and N(R.sup.7) with the proviso
that (CH(R.sup.14)).sub.j is bonded to the quinone ring;
[0188] E.sup.0 is E.sup.2, when K is (CH(R.sup.14)).sub.j-T,
wherein E.sup.2 is selected from the group consisting of C(O)N(H),
(H)NC(O), C(S)N(H), (H)NC(S), S(O).sub.2N(H), N(H)S(O).sub.2,
S(O).sub.2N(H)C(O), and C(O)N(H)S(O).sub.2;
[0189] R.sup.14 is selected from the group consisting of hydrido,
halo, alkyl, and haloalkyl;
[0190] Y.sup.0 is formula (IV): 17
[0191] wherein D.sup.5, D.sup.6, J.sup.5, and J.sup.6 are
independently selected from the group consisting of C, N, O, S and
a covalent bond with the provisos that no more than one can be a
covalent bond, K.sup.2 is independently selected from the group
consisting of C, and N.sup.+, no more than one of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 can be O, no more than one of D.sup.5,
D.sup.6, J.sup.5, and J.sup.6 can be S, one of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 must be a covalent bond when two of D.sup.5,
D.sup.6, J.sup.5, and J.sup.6 are O and S, no more than three of
D.sup.5, D.sup.6, J.sup.5, and J.sup.6 can be N when K.sup.2 is
N.sup.+, and no more than four of D.sup.5, D.sup.6, J.sup.5, and
J.sup.6 can be N when K.sup.2 is carbon with the provisos that
R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are each independently
selected to maintain the tetravalent nature of carbon, trivalent
nature of nitrogen, the divalent nature of sulfur, and the divalent
nature of oxygen;
[0192] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, amidino, guanidino,
dialkylsulfonium, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
thio, nitro, lower alkylamino, alkylthio, alkylsulfinyl,
alkylsulfonyl, alkanoyl, alkenoyl, haloalkanoyl, alkyl, alkenyl,
halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, aminoalkyl,
haloalkoxyalkyl, carboalkoxy, carboalkoxyalkyl, and cyano;
[0193] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, .sup.+NR.sup.20R.sup.21R.sup.22, oxy, alkyl,
alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, and acylamino
wherein R.sup.20, R.sup.21, and R.sup.22 are independently selected
from the group consisting of hydrido, alkyl, hydroxy, alkoxy,
alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl with the
provisos that no more than one of R.sup.20, R.sup.21, and R.sup.22
can be hydroxy, alkoxy, alkylamino, amino, and dialkylamino and
that R.sup.20, R.sup.21, and R.sup.22 must be other than be
hydroxy, alkoxy, alkylamino, amino, and dialkylamino when K.sup.2
is N.sup.+;
[0194] Q.sup.b can be N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24) with
the proviso that no more than one of R.sup.23, R.sup.24, and
R.sup.26 can be hydroxy, alkoxy, alkylamino, amino, or dialkylamino
when two of the group consisting of R.sup.23, R.sup.24, and
R.sup.26 are bonded to the same atom;
[0195] Q.sup.b can be selected from the group consisting of
dialkylsulfonium, trialkylphosphonium,
C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
N(R.sup.26)C(O)N(R.sup.23)(- R.sup.24),
N(R.sup.26)C(S)N(R.sup.23)(R.sup.24), C(O)N(R.sup.26)C(NR.sup.2-
5)N(R.sup.23)(R.sup.24),
C(S)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24),
C(O)NR.sup.23R.sup.24, and C(O)NR.sup.23R.sup.24 with the provisos
that no more than one of R.sup.23, R.sup.24, and R.sup.26 can be
hydroxy, alkoxy, alkylamino, amino, or dialkylamino when two of the
group consisting of R.sup.23, R.sup.24, and R.sup.26 are bonded to
the same atom and that said Q.sup.b group is bonded directly to a
carbon atom;
[0196] R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, alkyl, hydroxy,
alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl;
[0197] Q.sup.s is selected from the group consisting of a single
covalent bond and (CR.sup.37R.sup.38).sub.b--(W.sup.0).sub.az
wherein az is an integer selected from 0 through 1, b is an integer
selected from 1 through 2, and W.sup.0 is selected from the group
consisting of O, S, C(O), S(O).sub.2, N(R.sup.14), and ON(R.sup.14)
with the proviso that R.sup.14 is selected from other than halo
when directly bonded to N and that (CR.sup.37R.sup.38).sub.b is
bonded to E.sup.0;
[0198] R.sup.37 and R.sup.38 are independently selected from the
group consisting of hydrido, halo, alkyl, and haloalkyl;
[0199] Y.sup.0 can be Q.sup.b-Q.sup.ssss wherein Q.sup.ssss is
(CH(R.sup.38)).sub.r--W.sup.5, r is an integer selected from 1
through 2, and W.sup.5 is selected from the group consisting of
1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl,
2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl,
3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl,
2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,
3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,
2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,
2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,
3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,
2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,
3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,
2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,
1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,
3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,
2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,
3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,
1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl,
1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,
2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,
2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,
3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,
4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,
1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,
1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,
3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,
3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,
4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,
3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,
4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl
with the proviso that Q.sup.b is bonded to lowest number
substituent position of each W.sup.5 and that (CH(R.sup.38)).sub.r
is bonded to E.sup.0;
[0200] Y.sup.0 can be Q.sup.b-Q.sup.ssssr wherein Q.sub.ssssr is
(CH(R.sup.38)).sub.r--W.sup.6, r is an integer selected from 1
through 2, and W.sup.6 is selected from the group consisting of
1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl,
2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl,
3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl,
2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,
3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,
2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,
2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,
3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,
2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,
3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,
2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,
1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,
3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,
2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,
3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,
1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl,
1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,
2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,
2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,
3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,
4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,
1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,
1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,
3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,
3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,
4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,
3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,
4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl
with
[0201] the proviso that Q.sup.b is bonded to highest number
substituent position of each W and that (CH(R.sup.38)).sub.r is
bonded to E.sup.0.
[0202] In a more preferred embodiment of compounds of Formula I or
a pharmaceutically acceptable salt thereof,
[0203] B is selected from the group consisting of aryl and
heteroaryl wherein a carbon adjacent to the carbon at the point of
attachment may be substituted by R.sup.32, the other carbon
adjacent to the carbon at the point of attachment may be
substituted by R.sup.36, a carbon adjacent to R.sup.32 and two
atoms from the carbon at the point of attachment may be substituted
by R.sup.33, a carbon adjacent to R.sup.36 and two atoms from the
carbon at the point of attachment may be substituted by R.sup.35,
and any carbon adjacent to both R.sup.33 and R.sup.35 may be
substituted by R.sup.34;
[0204] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
amidino, guanidino, dialkylsulfonium, carboxy, haloalkylthio,
alkoxy, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino,
alkylthio, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkanoyl,
haloalkanoyl, alkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,
hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl,
carboalkoxy, carboxamido, and cyano;
[0205] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 can
independently be Q.sup.b;
[0206] B can be selected from the group consisting of C3-C8 alkyl,
C3-C8 alkenyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl wherein each
member of group B may be optionally substituted at any carbon up to
and including 6 atoms from the point of attachment of B to A with
one or more of the group consisting of R.sub.32, R.sub.33,
R.sub.34, R.sub.35, and R.sub.36;
[0207] B can be selected from the group consisting of C3-C10
cycloalkyl, C5-C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and
C4-C9 partially saturated heterocyclyl, wherein each ring carbon
may be optionally substituted with R.sub.33, a ring carbon other
than the ring carbon at the point of attachment of B to A may be
optionally substituted with oxo provided that no more than one ring
carbon is substituted by oxo at the same time, ring carbon and
nitrogen atoms adjacent to the carbon atom at the point of
attachment may be optionally substituted with R.sub.9 or R.sub.13,
a ring carbon or nitrogen atom adjacent to the R.sub.9 position and
two atoms from the point of attachment may be substituted with
R.sub.10, a ring carbon or nitrogen atom adjacent to the R.sub.13
position and two atoms from the point of attachment may be
substituted with R.sub.12, a ring carbon or nitrogen atom three
atoms from the point of attachment and adjacent to the R.sub.10
position may be substituted with R.sub.11 a ring carbon or nitrogen
atom three atoms from the point of attachment and adjacent to the
R.sub.12 position may be substituted with R.sub.33, and a ring
carbon or nitrogen atom four atoms from the point of attachment and
adjacent to the R.sub.11 and R.sub.33 positions may be substituted
with R.sub.34;
[0208] R.sup.9, R.sup.10, R.sup.11, R.sup.12, and R.sup.13 are
independently selected from the group consisting of hydrido,
amidino, guanidino, dialkylsulfonium, carboxy, haloalkylthio,
alkoxy, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino,
alkylthio, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkanoyl,
haloalkanoyl, alkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,
hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl,
carboalkoxy, carboxamido, and cyano;
[0209] A is selected from the group consisting of single covalent
bond, (W.sup.7).sub.rr--(CH(R.sup.15)).sub.pa and
(CH(R.sup.15)).sub.pa--(W.sup- .7).sub.rr wherein rr is an integer
selected from 0 through 1, pa is an integer selected from 0 through
6, and W.sup.7 is selected from the group consisting of O, S, and
C(O);
[0210] R.sup.15 is selected from the group consisting of hydrido,
hydroxy, halo, alkyl, and haloalkyl;
[0211] .PSI. is NH;
[0212] X.sup.0 is hydrido;
[0213] R.sup.2 is Q, wherein Q is selected from the group
consisting of aryl and heteroaryl wherein a carbon adjacent to the
carbon at the point of attachment may be substituted by R.sup.9,
the other carbon adjacent to the carbon at the point of attachment
may be substituted by R.sup.13, a carbon adjacent to R.sup.9 and
two atoms from the carbon at the point of attachment may be
substituted by R.sup.10, a carbon adjacent to R.sup.13 and two
atoms from the carbon at the point of attachment may be substituted
by R.sup.12, and any carbon adjacent to both R.sup.10 and R.sup.12
may be substituted by R.sup.11;
[0214] K is CR.sup.4aR.sup.4b wherein R.sup.4a and R.sup.4b are
independently selected from the group consisting of halo and
hydrido;
[0215] E.sup.0 is E.sup.1, when K is CR.sup.4aR.sup.4b, wherein
E.sup.1 is selected from the group consisting of a covalent single
bond, (O)N(H), (H)NC(O), S(O).sub.2N(H), N(H)S(O).sub.2,
S(O).sub.2N(H)C(O), and C(O)N(H)S(O).sub.2;
[0216] K can be (CH(R.sup.14)).sub.j-T wherein j is selected from
an integer from 0 through 1 and T is selected from the group
consisting of single covalent bond and N(R.sup.7) with the proviso
that (CH(R.sup.14)).sub.j is bonded to the quinone ring;
[0217] R.sup.7 is selected from the group consisting of hydrido,
hydroxy, alkyl, and alkoxyalkyl;
[0218] R.sup.14 is selected from the group consisting of hydrido
and halo;
[0219] E.sup.0 is E.sup.2, when K is (CH(R.sup.14)).sub.j-T,
wherein E.sup.2 is selected from the group consisting of C(O)N(H),
(H)NC(O), S(O).sub.2N(H), N(H)S(O).sub.2, S(O).sub.2N(H)C(O), and
C(O)N(H)S(O).sub.2;
[0220] Y.sup.0 is formula (IV): 18
[0221] wherein D.sup.5, D.sup.6, J.sup.5, and J.sup.6 are
independently selected from the group consisting of C, N, O, S and
a covalent bond with the provisos that no more than one can be a
covalent bond, K.sup.2 is independently selected from the group
consisting of C, and N.sup.+, no more than one of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 is O, no more than one of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 is S, one of D.sup.5, D.sup.6, J.sup.5, and
J.sup.6 must be a covalent bond when two of D.sup.5, D.sup.6,
J.sup.5, and J.sup.6 are O and S, no more than three of D.sup.5,
D.sup.6, J.sup.5, and J.sup.6 can be N when K.sup.2 is N.sup.+, and
no more than four of D.sup.5, D.sup.6, J.sup.5, and J.sup.6 can be
N when K.sup.2 is carbon with the provisos that R.sup.16, R.sup.17,
R.sup.18, and R.sup.19 are each independently selected to maintain
the tetravalent nature of carbon, trivalent nature of nitrogen, the
divalent nature of sulfur, and the divalent nature of oxygen;
[0222] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, amidino, guanidino,
dialkylsulfonium, carboxy, haloalkylthio, alkoxy, hydroxy, amino,
thio, nitro, lower alkylamino, alkylthio, alkylsulfinyl,
alkylsulfonyl, alkanoyl, alkenoyl, haloalkanoyl, alkyl, alkenyl,
halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, aminoalkyl,
haloalkoxyalkyl, carboalkoxy, carboalkoxyalkyl, and cyano;
[0223] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, NR.sup.20R.sup.21R.sup.22, oxy, alkyl,
alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, and acylamino
wherein R.sup.20, R.sup.21, and R.sup.22 are independently selected
from the group consisting of hydrido, alkyl, hydroxy, alkoxy,
alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl with the
provisos that no more than one of R.sup.20, R.sup.21, and R.sup.22
can be hydroxy, alkoxy, alkylamino, amino, and dialkylamino and
that R.sup.20, R.sup.21, and R.sup.22 must be other than be
hydroxy, alkoxy, alkylamino, amino, and dialkylamino when K.sup.2
is N.sup.+;
[0224] Q.sup.b can be selected from the group consisting of
dialkylsulfonium, trialkylphosphonium,
C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
C(O)N(R.sup.26)C(NR.sup.25)- N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)C(NR.sup.25R.sup.23)(R.sup.24- ),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24),
C(O)NR.sup.23R.sup.24, and C(O)NR.sup.23R.sup.24with the provisos
that no more than one of R.sup.23, R.sup.24, and R.sup.26 can be
hydroxy, alkoxy, alkylamino, amino, or dialkylamino when two of the
group consisting of R.sup.23, R.sup.24, and R.sup.26 are bonded to
the same atom and that said Q.sup.b group is bonded directly to a
carbon atom;
[0225] R.sup.23, R.sup.24, R.sup.25, and R.sup.26 are independently
selected from the group consisting of hydrido, alkyl, hydroxy,
alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl;
[0226] Q.sup.s is selected from the group consisting of a single
covalent bond and (CR.sup.37R.sup.38).sub.b--(W.sup.0).sub.az
wherein az is an integer selected from 0 through 1, b is the
integer 1, and W.sup.0 is selected from the group consisting of O,
S, and C(O) with the proviso that (CR.sup.37R.sup.38).sub.b is
bonded to E.sup.0;
[0227] R.sup.37 and R.sup.38 are independently selected from the
group consisting of hydrido, halo, alkyl, and haloalkyl.
[0228] In a specific embodiment of Formula I, compounds have the
Formula I-S: 19
[0229] or a pharmaceutically acceptable salt thereof, wherein;
[0230] B is selected from the group consisting of phenyl,
2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,
2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl,
1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,2,4-oxadiazol-3-yl,
1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl,
3-isothiazolyl, 5-isothiazolyl, 2-oxazolyl, 2-thiazolyl,
3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,
2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl,
3-pyridazinyl, 4-pyridazinyl, 1,3,5-triazin-2-yl,
1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl, and
1,2,3-triazin-yl, wherein a carbon adjacent to the carbon at the
point of attachment may be substituted by R.sup.32, the other
carbon adjacent to the carbon at the point of attachment may be
substituted by R.sup.36, a carbon adjacent to R.sup.32 and two
atoms from the carbon at the point of attachment may be substituted
by R.sup.33, a carbon adjacent to R.sup.36 and two atoms from the
carbon at the point of attachment may be substituted by R.sup.35,
and any carbon adjacent to both R.sup.33 and R.sup.35 may be
substituted by R.sup.34;
[0231] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
amidino, guanidino, dimethylsulfonium, carboxy, methoxy, ethoxy,
isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,
thio, nitro, aminomethyl, 1-aminoethyl, 2-aminoethyl,
N-N-methylamino, dimethylamino, N-ethylamino, methylthio,
ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl,
ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,
N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl,
propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,
2,2,2-trifluoro-1-trifluoromethyl-1-hydro- xyethyl, carboxymethyl,
methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and
Q.sup.b;
[0232] B can be selected from the group consisting of 1-propenyl,
propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl,
sec-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl,
3-pentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl,
1-methyl-2-butenyl, 1-methyl-3-butenyl, 1-methyl-2-butynyl,
3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl,
2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl,
3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl,
3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl,
2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl,
1-methyl-4-pentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl,
3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl,
1-ethyl-2-butynyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl,
5-heptenyl, 6-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl,
5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl,
1-methyl-4-hexenyl, 1-methyl-5-hexenyl, 1-methyl-2-hexynyl,
1-methyl-3-hexynyl, 1-methyl-4-hexynyl, 3-heptyl,
1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethylpentenyl,
1-butyl-2-propenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl,
1-octyl, 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl,
7-octenyl, 2-octynyl, 3-octynyl, 4-octynyl, 5-octynyl, 6-octynyl,
2-octyl, 1-methyl-2-heptenyl, 1-methyl-3-heptenyl,
1-methyl-4-heptenyl, 1-methyl-5-heptenyl, 1-methyl-6-heptenyl,
1-methyl-2-heptynyl, 1-methyl-3-heptynyl, 1-methyl-4-heptenyl,
1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-2-heptenyl,
1-methyl-3-heptynyl, 1-methyl-4-heptynyl, 1-methyl-5-heptynyl,
3-octyl, 1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethylhexenyl,
1-ethyl-2-hexynyl, 1-ethyl-3-hexynyl, 1-ethyl-4-hexynyl,
1-ethyl-5-hexenyl, 1-pentyl-2-propenyl, 4-octyl,
1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl,
1-butyl-2-butenyl, 1-propyl-2-pentynyl, 1-propyl-3-pentynyl,
1-butyl-2-butynyl, 1-butyl-3-butenyl, 2,2-difluoropropyl,
4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl,
5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein each
member of group B may be optionally substituted at any carbon up to
and including 5 atoms from the point of attachment of B to A with
one or more of the group consisting of R.sub.32, R.sub.33,
R.sub.34, R.sub.35 and R.sub.36;
[0233] B can be selected from the group consisting of cyclopropyl,
cyclobutyl, oxetan-2-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl,
azetidin-3-yl, thiaetan-2-yl, thiaetan-3-yl, cyclopentyl,
cyclopent-2-enyl, cyclopent-3-enyl, cyclohexyl, 4-methylcyclohexyl,
4-chloro-3-ethylphenoxycyclohexyl,
3-trifluoromethoxyphenoxycyclohexyl, 3-trifluoromethylcyclohexyl,
4-trifluoromethylcyclohexyl, 3,5-bis-trifluoromethylcyclohexyl,
adamantyl, 3-trifluoromethyladamantyl, norbornyl,
3-trifluoromethylnorbornyl, norbornenyl,
7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl,
cyclohex-2-enyl, cyclohex-3-enyl, cycloheptyl, cyclohept-2-enyl,
cyclohept-3-enyl, cyclooctyl, cyclooct-2-enyl, cyclooct-3-enyl,
cyclooct-4-enyl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl,
1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl,
3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl,
3-pyrrolidinyl, 2-dioxanyl, 2H-2-pyranyl, 2H-3-pyranyl, 2H-pyranyl,
4H-2-pyranyl, 4H-3-pyranyl, 4H-pyranyl, 2H-pyran-2-one-3-yl,
2H-pyran-2-one-4-yl, 2H-pyran-2-one-5-yl, 4H-pyran-4-one-2-yl,
4H-pyran-4one-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl,
2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl,
2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring
carbon may be optionally substituted with R.sub.33, a ring carbon
and nitrogen atoms adjacent to the carbon atom at the point of
attachment may be optionally substituted with R.sub.9 or R.sub.13,
a ring carbon or nitrogen atom adjacent to the R.sub.9 position and
two atoms from the point of attachment may be substituted with
R.sub.10, and a ring carbon or nitrogen atom adjacent to the
R.sub.13 position and two atoms from the point of attachment may be
substituted with R.sub.12;
[0234] R.sup.9, R.sup.10, R.sup.11, R.sup.12, and R.sup.13 are
independently selected from the group consisting of amidino,
guanidino, dimethylsulfonium, methylethylsulfonium, carboxy,
methoxy, ethoxy, isopropoxy, propoxy, butoxy, hydroxy, amino,
methoxyamino, ethoxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl,
N-N-dimethylamino, N-methylamino, N-ethylamino, methylsulfinyl,
ethylsulfinyl, methylsulfonyl, ethylsulfonyl, aminosulfonyl,
N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl,
propanoyl, butanoyl, trifluoroacetyl, pentafluoropropanoyl,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
2,2,2-trifluoro-1-hydroxyethyl,
2,2,2-trifluoro-1-trifluoromethyl-1-hydro- xyethyl, carboxymethyl,
2-carboxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;
[0235] A is selected from the group consisting of single covalent
bond, O, C(O), CH.sub.2, CH.sub.3CH, CF.sub.3CH, CH.sub.3CC(O),
CF.sub.3CC(O), C(O)CCH.sub.3, C(O)CCF.sub.3, CH.sub.2C(O),
(O)CCH.sub.2, CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2,
CH.sub.3CCH.sub.2, CF.sub.3CCH.sub.2, CH.sub.3CC(O)CH.sub.2,
CF.sub.3CC(O)CH.sub.2, CH.sub.2C(O)CCH.sub.3,
CH.sub.2C(O)CCF.sub.3, CH.sub.2CH.sub.2C(O), and
CH.sub.2(O)CCH.sub.2;
[0236] R.sup.2 is selected from the group consisting of phenyl,
2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,
2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl,
1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,2,4-oxadiazol-3-yl,
1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl,
3-isothiazolyl, 5-isothiazolyl, 2-oxazolyl, 2-thiazolyl,
3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,
2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl,
3-pyridazinyl, 4-pyridazinyl, 1,3,5-triazin-2-yl,
1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazin-yl, and
1,2,3-triazin-4-yl, wherein a carbon adjacent to the carbon at the
point of attachment may be substituted by R.sup.9, the other carbon
adjacent to the carbon at the point of attachment may be
substituted by R.sup.13, a carbon adjacent to R.sup.9 and two atoms
from the carbon at the point of attachment may be substituted by
R.sup.10, a carbon adjacent to R.sup.13 and two atoms from the
carbon at the point of attachment may be substituted by R.sup.12,
and any carbon adjacent to both R.sup.10 and R.sup.12 may be
substituted by R.sup.11;
[0237] K is CR.sup.4aR.sup.4b wherein R.sup.4a and R.sup.4b are
independently selected from the group consisting of chloro, fluoro,
and hydrido;
[0238] E.sup.0 is E.sup.1, when K is CR.sup.4aR.sup.4b, wherein
E.sup.1 is selected from the group consisting of a covalent single
bond, C(O)N(H), (H)NC(O), S(O).sub.2N(H), N(H)S(O).sub.2,
S(O).sub.2N(H)C(O), and C(O)N(H)S(O).sub.2;
[0239] K can be N(H) and CH.sub.2N(H);
[0240] E.sup.0 is E.sup.2, when K is N(H) and CH.sub.2N(H), wherein
E.sup.2 is selected from the group consisting of C(O)N(H),
(H)NC(O), S(O).sub.2N(H), N(H)S(O).sub.2, S(O).sub.2N(H)C(O), and
C(O)N(H)S(O).sub.2;
[0241] Y.sup.0 is selected from the group of formulas consisting
of: 2021
[0242] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, amidino, guanidino,
dimethylsulfonium, carboxy, methoxy, ethoxy, isopropoxy, propoxy,
hydroxy, amino, methoxyamino, ethoxyamino, thio, nitro,
aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N-methylamino,
dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,
trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,
ethylsulfonyl, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,
acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
2,2,2-trifluoro-1-hydroxyethyl,
2,2,2-trifluoro-1-trifluoromethyl-1-hydro- xyethyl, carboxymethyl,
methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;
[0243] Q.sup.b is selected, when bonded to a carbon, from the group
consisting of NR.sup.20R.sup.21, .sup.+NR.sup.20R.sup.21R.sup.22,
dimethylsulfonium, methylethylsulfonium, diethylsulfonium,
trimethylphosphonium, C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
C(O)N(R.sup.26)C(NR.sup.25)- N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup- .24),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24),
C(O)NR.sup.23R.sup.24, and C(O)NR.sup.23R.sup.24 with the provisos
that no more than one of R.sup.20, R.sup.21, and R.sup.22 can be
hydroxy, methoxy, ethoxy, N-methylamino, N,N-dimethylamino, and
N,N,N-trimethylamino, and amino and that no more than one of
R.sup.23, R.sup.24, and R.sup.26 can be hydroxy, methoxy, ethoxy,
N-methylamino, N,N-dimethylamino, N,N,N-trimethylamino, or amino
when two of the group consisting of R.sup.23, R.sup.24, and
R.sup.26 are bonded to the same atom and that said Q.sup.b group is
bonded directly to a carbon atom;
[0244] R.sup.20, R.sup.21, R.sup.22, R.sup.23, R.sup.24, R.sup.25,
and R.sup.26 are independently selected from the group consisting
of hydrido, methyl, ethyl, propyl, butyl, isopropyl, hydroxy,
methoxy, ethoxy, isopropoxy, propoxy, 2-aminoethyl,
2-(N-methylamino)ethyl, 2-(N,N-dimethylamino)ethyl,
2-(N,N,N-trimethylamino)ethyl, N-(2-hydroxyethyl)amino,
N,N-bis-(2-hydroxyethyl)amino,
N-(2-hydroxyethyl)-N-(2-aminoethyl)amino, N-methylamino,
N-ethylamino, N,N-dimethylamino, N,N-diethylamino, and
N,N,N-trimethylamino;
[0245] Q.sup.b is selected, when bonded to a nitrogen, from the
group consisting of oxy, methyl, ethyl, 2-aminoethyl,
2-(N-methylamino)ethyl, 2-(N,N-dimethylamino)ethyl,
2-(N,N,N-trimethylamino)ethyl, N-(2-hydroxyethyl)amino,
N,N-bis-(2-hydroxyethyl)amino, amino, hydroxylamino,
N-methoxyamino, N-methylamino, N,N-dimethylamino, and
N,N,N-trimethylamino;
[0246] Q.sup.s is selected from the group consisting of a single
covalent bond, CH.sub.2, CH.sub.3CH, CF.sub.2, CF.sub.3CH,
CH.sub.2O, CH.sub.3C(H)O, CF.sub.3C(H)O, CH.sub.2S, CH.sub.3C(H)S,
CF.sub.3C(H)S, CH.sub.2C(O), CH.sub.3C(H)C(O), CF.sub.3C(H)C(O),
and CF.sub.2C(O) with the proviso that Q.sup.s is bonded to E.sup.0
through a carbon atom.
[0247] In a more preferred specific embodiment of Formula I,
compounds have the Formula I-MPS: 22
[0248] or a pharmaceutically acceptable salt thereof, wherein;
[0249] B is selected from the group consisting of phenyl,
2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,
2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl,
3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,
2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl,
3-pyridazinyl, 4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a
carbon adjacent to the carbon at the point of attachment may be
substituted by R.sup.32, the other carbon adjacent to the carbon at
the point of attachment may be substituted by R.sup.36, a carbon
adjacent to R.sup.32 and two atoms from the carbon at the point of
attachment may be substituted by R.sup.33, a carbon adjacent to
R.sup.36 and two atoms from the carbon at the point of attachment
may be substituted by R.sup.35, and any carbon adjacent to both
R.sup.33 and R.sup.35 may be substituted by R.sup.34;
[0250] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
amidino, guanidino, dimethylsulfonium, carboxy, methoxy, ethoxy,
isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,
thio, nitro, aminomethyl, 1-aminoethyl, 2-aminoethyl,
N-N-methylamino, dimethylamino, N-ethylamino, methylthio,
ethylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl,
methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,
acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
2,2,2-trifluoro-1-hydroxyethyl,
2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl,
methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and
Q.sup.b;
[0251] B can be selected from the group consisting of 1-propenyl,
propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, sec-butyl,
isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl,
4-pentenyl, 2-pentyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl,
3-pentyl, 1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl,
2-methyl-3-butenyl, 3-methylbutyl, 3-methyl-2-butenyl,
3-methyl-3-butenyl, 2,2-difluoropropyl,
2-trifluoromethyl-3,3,3-trifluoropropyl,
1,1,1,2,2,2-hexafluoropropyl, 3,3,3-trifluoroprop-1-yl, and
3,3,3-trifluoroprop-2-yl, wherein each member of group B may be
optionally substituted at any carbon up to and including 5 atoms
from the point of attachment of B to A with one or more of the
group consisting of R.sub.32, R.sub.33, R.sub.34, R.sub.35, and
R.sub.36;
[0252] B can be selected from the group consisting of cyclopropyl,
cyclobutyl, oxetan-2-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl,
azetidin-3-yl, thiaetan-2-yl, thiaetan-3-yl, wherein each ring
carbon may be optionally substituted with R.sub.33, a ring carbon
and nitrogen atoms adjacent to the carbon atom at the point of
attachment may be optionally substituted with R.sub.9 or R.sub.13,
a ring carbon or nitrogen atom adjacent to the R.sub.9 position and
two atoms from the point of attachment may be substituted with
R.sub.10, and a ring carbon or nitrogen atom adjacent to the
R.sub.13 position and two atoms from the point of attachment may be
substituted with R.sub.12;
[0253] R.sup.9, R.sup.10, R.sup.11, R.sup.12, and R.sup.13 are
independently selected from the group consisting of amidino,
guanidino, dimethylsulfonium, carboxy, methoxy, ethoxy, isopropoxy,
propoxy, hydroxy, amino, methoxyamino, ethoxyamino, aminomethyl,
1-aminoethyl, 2-aminoethyl, N-N-methylamino, dimethylamino,
N-ethylamino, methylsulfinyl, ethylsulfinyl, methylsulfonyl,
ethylsulfonyl, amidosulfonyl, N-methylamidosulfonyl,
N,N-dimethylamidosulfonyl, acetyl, propanoyl, trifluoroacetyl,
pentafluoropropanoyl, hydroxymethyl, 1-hydroxyethyl,
2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,
2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl,
methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;
[0254] A is selected from the group consisting of single covalent
bond, O, C(O), CH.sub.2, CH.sub.3CH, CF.sub.3CH, CH.sub.3CC(O),
CF.sub.3CC(O), C C(O)CCH.sub.3, C(O)CCF.sub.3, CH.sub.2C(O), and
(O)CCH.sub.2;
[0255] R.sup.2 is selected from the group consisting of phenyl,
2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,
2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl,
3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,
2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl,
3-pyridazinyl, 4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a
carbon adjacent to the carbon at the point of attachment may be
substituted by R.sup.9, the other carbon adjacent to the carbon at
the point of attachment may be substituted by R.sup.13, a carbon
adjacent to R.sup.9 and two atoms from the carbon at the point of
attachment may be substituted by R.sup.10, a carbon adjacent to
R.sup.13 and two atoms from the carbon at the point of attachment
may be substituted by R.sup.12, and any carbon adjacent to both
R.sup.10 and R.sup.12 may be substituted by R.sup.11;
[0256] K is CR.sup.4aR.sup.4b wherein R.sup.4a and R.sup.4b are
independently selected from the group consisting of chloro, fluoro,
and hydrido;
[0257] E.sup.0 is E.sup.1, when K is CR.sup.4aR.sup.4b, wherein
E.sup.1 is selected from the group consisting of a covalent single
bond, C(O)N(H), (H)NC(O), S(O).sub.2N(H), N(H)S(O).sub.2,
S(O).sub.2N(H)C(O), and C(O)N(H)S(O).sub.2;
[0258] K can be N(H) and CH.sub.2N(H);
[0259] E.sup.0 is E.sup.2, when K is N(H) and CH.sub.2N(H), wherein
E.sup.2 is selected from the group consisting of C(O)N(H),
(H)NC(O), S(O).sub.2N(H), N(H)S(O).sub.2, S(O).sub.2N(H)C(O), and
C(O)N(H)S(O).sub.2;
[0260] Y.sup.0 is selected from the group of formulas consisting
of: 2324
[0261] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, amidino, guanidino,
methoxy, ethoxy, isopropoxy, methylthio, ethylthio,
trifluoromethylthio, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl,
methoxycarbonyl, ethoxycarbonyl, and cyano;
[0262] Q.sup.b is selected, when bonded to a carbon, from the group
consisting of NR.sup.20R.sup.21, .sup.+NR.sup.20R.sup.21R.sup.22,
dimethylsulfonium, methylethylsulfonium, diethylsulfonium,
trimethylphosphonium, C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
C(O)N(R.sup.26)C(N.sup.25)N- (R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.- 24),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24),
C(O)NR.sup.23R.sup.24, and C(O)NR.sup.23R.sup.24 with the provisos
that no more than one of R.sup.20, R.sup.21, and R.sup.22 can be
hydroxy, methoxy, ethoxy, N-methylamino, N,N-dimethylamino,
N,N,N-trimethylamino, or amino and that no more than one of
R.sup.23, R.sup.24, and R.sup.26 can be hydroxy, methoxy, ethoxy,
N-methylamino, N,N-dimethylamino, N,N,N-trimethylamino, or amino
when two of the group consisting of R.sup.23, R.sup.24, and
R.sup.26 are bonded to the same atom and that said Q.sup.b group is
bonded directly to a carbon atom;
[0263] R.sup.20, R.sup.21, R.sup.22, R.sup.23, R.sup.24, R.sup.25,
and R.sup.26 are independently selected from the group consisting
of hydrido, methyl, ethyl, hydroxy, methoxy, ethoxy, 2-aminoethyl,
2-(N-methylamino)ethyl, 2-(N,N-dimethylamino)ethyl,
2-(N,N,N-trimethylamino)ethyl, N-(2-hydroxyethyl)amino,
N,N-bis-(2-hydroxyethyl)amino,
N-(2-hydroxyethyl)-N-(2-aminoethyl)amino, N-methylamino,
N,N-dimethylamino, and N,N,N-trimethylamino;
[0264] Q.sup.b is selected, when bonded to a nitrogen, from the
group consisting of oxy, methyl, ethyl, 2-aminoethyl,
2-(N-methylamino)ethyl, 2-(N,N-dimethylamino)ethyl,
2-(N,N,N-trimethylamino)ethyl, N-(2-hydroxyethyl)amino,
N,N-bis-(2-hydroxyethyl)amino, amino, hydroxylamino,
N-methoxyamino, N-methylamino, N,N-dimethylamino, and
N,N,N-trimethylamino;
[0265] Q.sup.s is selected from the group consisting of a single
covalent bond, CH.sub.2, CH.sub.3CH, CF.sub.2, CF.sub.3CH,
CH.sub.2O, CH.sub.3C(H)O, CF.sub.3C(H)O, CH.sub.2S, CH.sub.3C(H)S,
CF.sub.3C(H)S, CH.sub.2C(O), CH.sub.3C(H)C(O), CF.sub.3C(H)C(O),
and CF.sub.2C(O) with the proviso that Q.sup.s is bonded to E.sup.0
through a carbon atom.
[0266] In an even more preferred specific embodiment of compounds
of Formula I, compounds have the Formula I-EMPS: 25
[0267] or a pharmaceutically acceptable salt thereof, wherein;
[0268] B is selected from the group consisting of phenyl,
2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,
2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl,
3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, and 4-pyridyl,
wherein a carbon adjacent to the carbon at the point of attachment
may be substituted by R.sup.32, the other carbon adjacent to the
carbon at the point of attachment may be substituted by R.sup.36, a
carbon adjacent to R.sup.32 and two atoms from the carbon at the
point of attachment may be substituted by R.sup.33, a carbon
adjacent to R.sup.36 and two atoms from the carbon at the point of
attachment may be substituted by R.sup.35, and any carbon adjacent
to both R.sup.33 and R.sup.35 may be substituted by R.sup.34;
[0269] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
amidino, guanidino, methoxy, ethoxy, hydroxy, amino, methoxyamino,
ethoxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl,
N-N-methylamino, dimethylamino, N-ethylamino, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, fluoro, chloro, bromo, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,
2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, methoxycarbonyl,
ethoxycarbonyl, cyano, and Q.sup.b;
[0270] B can be selected from the group consisting of propyl,
isopropyl, butyl, sec-butyl, isobutyl, 1-pentyl, 2-pentyl,
3-pentyl, 2-methylbutyl, 3-methylbutyl, 2,2-difluoropropyl,
2-trifluoromethyl-3,3,3-trifluoropropy- l,
1,1,1,2,2,2-hexafluoropropyl, 3,3,3-trifluoroprop-1-yl, and
3,3,3-trifluoroprop-2-yl, wherein each member of group B may be
optionally substituted at any carbon up to and including 5 atoms
from the point of attachment of B to A with one or more of the
group consisting of R.sub.32, R.sub.33, R.sub.34, R.sub.35, and
R.sub.36;
[0271] B can be selected from the group consisting of cyclopropyl,
cyclobutyl, oxetan-2-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl,
azetidin-3-yl, thiaetan-2-yl, thiaetan-3-yl, wherein each ring
carbon may be optionally substituted with R.sub.33, a ring carbon
and nitrogen atoms adjacent to the carbon atom at the point of
attachment may be optionally substituted with R.sub.9 or R.sub.13,
a ring carbon or nitrogen atom adjacent to the R.sub.9 position and
two atoms from the point of attachment may be substituted with
R.sub.10, and a ring carbon or nitrogen atom adjacent to the
R.sub.13 position and two atoms from the point of attachment may be
substituted with R.sub.12;
[0272] R.sup.9, R.sup.10, R.sup.11, R.sup.12, and R.sup.13 are
independently selected from the group consisting of amidino,
guanidino, carboxy, methoxy, ethoxy, hydroxy, amino, methoxyamino,
ethoxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl,
N-N-methylamino, dimethylamino, N-ethylamino, acetyl, propanoyl,
trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, carboxymethyl, methoxycarbonyl,
ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,
N,N-dimethylamidocarbonyl, and cyano;
[0273] A is selected from the group consisting of single covalent
bond, O, C(O), CH.sub.2, CH.sub.2C(O), and (O)CCH.sub.2;
[0274] R.sup.2 is selected from the group consisting of phenyl,
2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,
2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl,
3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,
2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl,
3-pyridazinyl, 4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a
carbon adjacent to the carbon at the point of attachment may be
substituted by R.sup.9, the other carbon adjacent to the carbon at
the point of attachment may be substituted by R.sup.13, a carbon
adjacent to R.sup.9 and two atoms from the carbon at the point of
attachment may be substituted by R.sup.20, a carbon adjacent to
R.sup.13 and two atoms from the carbon at the point of attachment
may be substituted by R.sup.12, and any carbon adjacent to both
R.sup.10 and R.sup.12 may be substituted by R.sup.11;
[0275] K is CR.sup.4aR.sup.4b wherein R.sup.4a and R.sup.4b are
independently selected from the group consisting of chloro, fluoro,
and hydrido;
[0276] E.sup.0 is E.sup.1, when K is CR.sup.4aR.sup.4b, wherein
E.sup.1 is selected from the group consisting of a covalent single
bond, C(O)N(H), (H)NC(O), S(O).sub.2N(H), N(H)S(O).sub.2,
S(O).sub.2N(H)C(O), and C(O)N(H)S(O).sub.2;
[0277] K can be N(H) and CH.sub.2N(H);
[0278] E.sup.0 is E.sup.2, when K is N(H) and CH.sub.2N(H), wherein
E.sup.2 is selected from the group consisting of C(O)N(H),
(H)NC(O), S(O).sub.2N(H), N(H)S(O).sub.2, S(O).sub.2N(H)C(O), and
C(O)N(H)S(O).sub.2;
[0279] Y.sup.0 is selected from the group of formulas consisting
of: 2627
[0280] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, methoxy, ethoxy,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,
trifluoromethoxy, fluoro, chloro, bromo, acetyl, trifluoroacetyl,
methoxycarbonyl, ethoxycarbonyl, and cyano;
[0281] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, .sup.+NR.sup.20R.sup.21R.sup.22,
dimethylsulfonium, methylethylsulfonium, diethylsulfonium,
trimethylphosphonium, C(NR.sup.25)NR.sup.23R.sup.24,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24),
C(O)N(R.sup.26)C(NR.sup.25)- N(R.sup.23)(R.sup.24),
N(R.sup.26)N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup- .24),
N(R.sup.26)N(R.sup.26)SO.sub.2N(R.sup.23)(R.sup.24),
C(O)NR.sup.23R.sup.24, and C(O)NR.sup.23R.sup.24 with the provisos
that no more than one of R.sup.20, R.sup.21, and R.sup.22 can be
hydroxy, methoxy, ethoxy, N-methylamino, N,N-dimethylamino,
N,N,N-trimethylamino, or amino and that no more than one of
R.sup.23, R.sup.24, and R.sup.26 can be hydroxy, methoxy, ethoxy,
N-methylamino, N,N-dimethylamino, N,N,N-trimethylamino, or amino
when two of the group consisting of R.sup.23, R.sup.24, and
R.sup.26 are bonded to the same atom and that said Q.sup.b group is
bonded directly to a carbon atom;
[0282] R.sup.20, R.sup.21, R.sup.22, R.sup.23, R.sup.24, R.sup.25,
and R.sup.26 are independently selected from the group consisting
of hydrido, methyl, ethyl, hydroxy, methoxy, ethoxy, 2-aminoethyl,
2-(N-methylamino)ethyl, 2-(N,N-dimethylamino)ethyl,
2-(N,N,N-trimethylamino)ethyl, N-(2-hydroxyethyl)amino,
N,N-bis-(2-hydroxyethyl)amino,
N-(2-hydroxyethyl)-N-(2-aminoethyl)amino, N-methylamino,
N,N-dimethylamino, and N,N,N-trimethylamino;
[0283] Q.sup.s is selected from the group consisting of a single
covalent bond, CH.sub.2, CH.sub.3CH, CF.sub.2, CF.sub.3CH,
CH.sub.2O, CH.sub.3C(H)O, CF.sub.3C(H)O, CH.sub.2C(O),
CH.sub.3C(H)C(O), CF.sub.3C(H)C(O), and CF.sub.2C(O) with the
proviso that Q.sup.s is bonded to E.sup.0 through a carbon
atom.
[0284] In a preferred embodiment of a compound of Formula I, said
compound is the Formula: 28
[0285] or a pharmaceutically acceptable salt thereof, wherein;
[0286] B is phenyl or a heteroaryl of 5 or 6 ring members, wherein
a nitrogen with a removable hydrogen or a carbon adjacent to the
carbon at the point of attachment of said phenyl or heteroaryl ring
to A is optionally substituted by R.sup.32, a nitrogen with a
removable hydrogen or a carbon at the other position adjacent to
the point of attachment is optionally substituted by R.sup.36, a
nitrogen with a removable hydrogen or a carbon adjacent to R.sup.32
and two atoms from the point of attachment is optionally
substituted by R.sup.33, a nitrogen with a removable hydrogen or a
carbon adjacent to R.sup.36 and two atoms from the point of
attachment is optionally substituted by R.sup.35, and a nitrogen
with a removable hydrogen or a carbon adjacent to both R.sup.33 and
R.sup.35 is optionally substituted by R.sup.34;
[0287] R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.32,
R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are independently
selected from the group consisting of hydrido, acetamido,
haloacetamido, amidino, guanidino, alkylenedioxy, haloalkylthio,
alkanoyloxy, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy,
aryloxy, heteroaryloxy, heteroaralkoxy,heterocyclyloxy,
heterocyclylalkoxy, alkoxyalkyl, haloalkoxylalkyl, hydroxy, amino,
alkoxyamino, nitro, alkylamino, N-alkyl-N-arylamino, arylamino,
aralkylamino, heteroarylamino, heteroaralkylamino,
heterocyclylamino, heterocyclylalkylamino, alkylthio,
alkylthioalkyl, alkylsulfinyl, arylsulfinyl, aralkylsulfinyl,
cycloalkylsulfinyl, heteroarylsulfinyl, alkylsulfonyl,
arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl,
heteroarylsulfonyl, alkylsulfonylalkyl, aryl, aralkyl, cycloalkyl,
cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido,
amidosulfonyl, alkanoyl, haloalkanoyl, alkyl, alkenyl, halo,
haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl,
aminoalkyl, haloalkoxyalkyl, carboxyalkyl, carboalkoxy, carboxy,
carboxamido, carboxamidoalkyl, and cyano;
[0288] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently optionally Q.sup.b;
[0289] B is optionally selected from the group consisting of
hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8
alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of
group B is optionally substituted at any carbon up to and including
6 atoms from the point of attachment of B to A with one or more of
the group consisting of R.sup.32, R.sup.33, R.sup.34, R.sup.35, and
R.sup.36;
[0290] B is optionally a C3-C12 cycloalkyl or C4-C9 saturated
heterocyclyl, wherein each ring carbon is optionally substituted
with R.sup.33, a ring carbon other than the ring carbon at the
point of attachment of B to A is optionally substituted with oxo
provided that no more than one ring carbon is substituted by oxo at
the same time, ring carbons and a nitrogen adjacent to the carbon
atom at the point of attachment are optionally substituted with
R.sup.9 or R.sup.13, a ring carbon or nitrogen atom adjacent to the
R.sup.9 position and two atoms from the point of attachment is
optionally substituted with R.sup.10, a ring carbon or nitrogen
adjacent to the R.sup.13 position and two atoms from the point of
attachment is optionally substituted with R.sup.12, a ring carbon
or nitrogen three atoms from the point of attachment and adjacent
to the R.sup.10 position is optionally substituted with R.sup.11, a
ring carbon or nitrogen three atoms from the point of attachment
and adjacent to the R.sup.12 position is optionally substituted
with R.sup.33, and a ring carbon or nitrogen four atoms from the
point of attachment and adjacent to the R.sup.11 and R.sup.33
positions is optionally substituted with R.sup.34;
[0291] A is selected from the group consisting of a bond,
(W.sup.7).sub.rr--(CH(R.sup.15)).sub.pa; and
(CH(R.sup.15)).sub.pa--(W.su- p.7).sub.rr wherein rr is 0 or 1, pa
is an integer selected from 0 through 6, and W.sup.7 is selected
from the group consisting of O, S, C(O), (R.sup.7)NC(O),
(R.sup.7)NC(S), and N(R.sup.7) with the proviso that no more than
one of the group consisting of rr and pa is 0 at the same time;
[0292] R.sup.7 is selected from the group consisting of hydrido,
hydroxy, and alkyl;
[0293] R.sup.15 is selected from the group consisting of hydrido,
hydroxy, halo, alkyl, and haloalkyl;
[0294] .PSI. is NH or NOH;
[0295] X.sup.0 is selected from the group consisting of hydrido,
alkyl, alkenyl, cyano, halo, haloalkyl, haloalkoxy, haloalkylthio,
amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino,
alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio;
[0296] R.sup.2 is Z.sup.0-Q;
[0297] Z.sup.0 is selected from the group consisting of a bond,
(CR.sup.41R.sup.42).sub.q wherein q is an integer selected from 1
through 3, and (CH(R.sup.41)).sub.g--W.sup.0--(CH(R.sup.42)).sub.p
wherein g and p are integers independently selected from 0 through
3 and W.sup.0 is selected from the group consisting of O, S, C(O),
S(O), N(R.sup.41), and ON(R.sup.41);
[0298] Z.sup.0 is optionally
(CH(R.sup.41)).sub.e--W.sup.22--(CH(R.sup.42)- ).sub.h wherein e
and h are independently 0 or 1 and W.sup.22 is selected from the
group consisting of CR.sup.41.dbd.CR.sup.42, 1,2-cyclopropyl,
1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl,
1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl,
3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl,
2,3-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl,
2,4-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl,
1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,
2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, wherein Z.sup.0
is directly bonded to the 1,4-quinone ring and W.sup.22 is
optionally substituted with one or more substituents selected from
the group consisting of R.sup.9, R.sup.10, R.sup.11, R.sup.12, and
R.sup.13;
[0299] R.sup.41 and R.sup.42 are independently selected from the
group consisting of amidino, hydroxyamino, hydrido, hydroxy, amino,
and alkyl;
[0300] Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein
a nitrogen with a removable hydrogen or a carbon adjacent to the
carbon at the point of attachment of said phenyl or heteroaryl ring
to Z.sup.0 is optionally substituted by R.sup.9, a nitrogen with a
removable hydrogen or a carbon at the other position adjacent to
the point of attachment is optionally substituted by R.sup.13, a
nitrogen with a removable hydrogen or a carbon adjacent to R.sup.9
and two atoms from the point of attachment is optionally
substituted by R.sup.10, a nitrogen with a removable hydrogen or a
carbon adjacent to R.sup.13 and two atoms from the point of
attachment is optionally substituted by R.sup.12, and a nitrogen
with a removable hydrogen or a carbon adjacent to both R.sup.10 and
R.sup.12 is optionally substituted by R.sup.11;
[0301] Q is optionally hydrido with the proviso that Z.sup.0 is
selected from other than a bond;
[0302] K is CR.sup.4aCR.sup.4b;
[0303] R.sup.4a and R.sup.4b are independently selected from the
group consisting of halo, hydrido, hydroxyalkyl, alkyl,
alkoxyalkyl, alkylthioalkyl, and haloalkyl;
[0304] E.sup.0, with the proviso that K is CR.sup.4aR.sup.4b, is
E.sup.1 wherein E.sup.1 is selected from the group consisting of a
covalent single bond, C(O)N(H), (H)NC(O), C(S)N(H), (H)NC(S),
S(O).sub.2N(H), N(H)S(O).sub.2, S(O).sub.2N(H)C(O), and
C(O)N(H)S(O).sub.2;
[0305] K is optionally (CH(R.sup.14)).sub.j-T wherein j is 0 or 1
and T is a bond or N(R.sup.7) with the proviso that
(CH(R.sup.14)).sub.j is bonded to the phenyl ring;
[0306] R.sup.14 is selected from the group consisting of hydrido,
halo, alkyl, and haloalkyl;
[0307] E.sup.0, with the proviso that K is (CH(R.sup.14)).sub.j-T,
is E.sup.2 wherein E.sup.2 is selected from the group consisting of
C(O)N(H), (H)NC(O), C(S)N(H), (H)NC(S), S(O).sub.2N(H),
N(H)S(O).sub.2, S(O).sub.2N(H)C(O), and C(O)N(H)S(O).sub.2;
[0308] Y.sup.0 is phenyl or a heteroaryl of 5 or 6 ring members,
wherein one carbon of said phenyl or said heteroaryl is substituted
by Q.sup.s, a carbon two or three contiguous atoms from the point
of attachment of Q.sup.s to said phenyl or said heteroaryl to said
phenyl or said heteroaryl is substituted by Q.sup.b, a carbon
adjacent to the point of attachment of Q.sup.s is optionally
substituted by R.sup.17, another carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.18, a
carbon adjacent to Q.sup.b is optionally substituted by R.sup.16,
and another carbon adjacent to Q.sup.b is optionally substituted by
R.sup.19;
[0309] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, amidino, guanidino,
carboxy, haloalkylthio, alkoxy, hydroxy, amino, nitro, alkoxyamino,
alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl,
haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkoxy,
hydroxyalkyl, aminoalkyl, haloalkoxyalkyl, carboalkoxy, and
cyano;
[0310] R.sup.16 or R.sup.19 is optionally selected from the group
consisting of NR.sup.20R.sup.21,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup- .24), and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido;
[0311] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, aminoalkyl, hydrido,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24), and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that no more than
one of R.sup.20 and R.sup.21 is selected from the group consisting
of hydroxy, amino, alkylamino, and dialkylamino at the same time,
with the further proviso that no more than one of R.sup.23 and
R.sup.24 is selected from the group consisting of hydroxy, amino,
alkylamino, and dialkylamino at the same time;
[0312] R.sup.20, R.sup.21, R.sup.23, R.sup.24, R.sup.25, and
R.sup.26 are independently selected from the group consisting of
hydrido, alkyl, hydroxy, aminoalkyl, amino, dialkylamino,
alkylamino, and hydroxyalkyl;
[0313] Q.sup.s is selected from the group consisting of a bond,
(CR.sup.37R.sup.38).sub.b wherein b is an integer selected from 1
through 4, and (CH(R.sup.14)).sub.c--W.sup.1--(CH(R.sup.15)).sub.d
wherein c and d are integers independently selected from 1 through
3 and W.sup.1 is selected from the group consisting of
C(O)N(R.sup.14), (R.sup.14)NC(O), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, and N(R.sup.14), with
the proviso that R.sup.14 is selected from other than halo when
directly bonded to N, and with the additional proviso that
(CR.sup.37R.sup.38).sub.b and (CH(R.sup.14)).sub.c are bonded to
E.sup.0;
[0314] R.sup.37 and R.sup.38 are independently selected from the
group consisting of hydrido, alkyl, and haloalkyl;
[0315] R.sup.38 is optionally aroyl or heteroaroyl, wherein
R.sup.38 is optionally substituted with one or more substituents
selected from the group consisting of R.sup.16, R.sup.17, R.sup.18,
and R.sup.19;
[0316] Y.sup.0 is optionally Y.sup.AT wherein Y.sup.AT is
Q.sup.b-Q.sup.s;
[0317] Y.sup.0 is optionally Q.sup.b-Q.sup.ss wherein Q.sup.ss is
(CH(R.sup.14)).sub.e--W.sup.2--(CH(R.sup.15)).sub.h, wherein e and
h are independently 1 or 2 and W.sup.2 is CR.sup.4a.dbd.CR.sup.4b,
with the proviso that (CH(R.sup.14)).sub.e is bonded to
E.sup.0;
[0318] Y.sup.0 is optionally Q.sup.b-Q.sup.ssss or
Q.sup.b-Q.sup.ssssr wherein Q.sup.ssss is
(CH(R.sup.38)).sub.r--W.sup.5, Q.sup.ssssr is
(CH(R.sup.38)).sub.r--W.sup.6, r is 1 or 2, W.sup.5 and W.sup.6 are
independently selected from the group consisting of 1,4-indenyl,
1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl,
2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl,
3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl,
2,7-benzofuranyl, 3,4-benzofuranyl, 3,5-benzofuranyl,
3,6-benzofuranyl, 3,7-benzofuranyl, 2,4-benzothiophenyl,
2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7-benzothiophenyl,
3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6-benzothiophenyl,
3,7-benzothiophenyl, 2,7-imidazo(1,2-a)pyridinyl,
3,4-imidazo(1,2-a)pyridinyl, 3,5-imidazo(1,2-a)pyridinyl,
3,6-imidazo(1,2-a)pyridinyl, 3,7-imidazo(1,2-a)pyridinyl,
2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl,
3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl,
1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl,
2,6-isoindolyl, 2,7-isoindolyl, 1,3-isoindolyl, 3,4-indazolyl,
3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl,
2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl,
3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl,
3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl,
1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl,
2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl,
2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 5
3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl,
3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl,
4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl,
1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl,
3,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl,
3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl,
4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8-isoquinolinyl,
3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl,
3,8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and
4,8-cinnolinyl, and each carbon and hyrido containing nitrogen
member of the ring of the W.sup.5 and of the ring of the W.sup.6,
other than the points of attachment of W.sup.5 and W.sup.6, is
optionally substituted with one or more of the group consisting of
R.sup.9, R.sup.10, R.sup.11, and R.sup.12, with the proviso that
Q.sup.b is bonded to lowest number substituent position of each
W.sup.5, with the further proviso that Q.sup.b is bonded to highest
number substituent position of each W.sup.6, and with the
additional proviso that (CH(R.sup.38)).sub.r is bonded to
E.sup.0.
[0319] In a more preferred embodiment of a compound of Formula I,
said compound is the Formula: 29
[0320] or a pharmaceutically acceptable salt thereof, wherein;
[0321] B is phenyl or a heteroaryl of 5 or 6 ring members, wherein
a carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to A is optionally substituted by
R.sup.32, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.36, a carbon adjacent
to R.sup.32 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.33, a carbon adjacent
to R.sup.36 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.35, and any carbon
adjacent to both R.sup.33 and R.sup.35 is optionally substituted by
R.sup.34;
[0322] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
acetamido, haloacetamido, amidino, guanidino, alkylenedioxy,
haloalkylthio, alkanoyloxy, alkoxy, hydroxy, amino, alkoxyamino,
haloalkanoyl, nitro, alkylamino, alkylthio, aryl, aralkyl,
cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl,
alkylsulfonamido, amidosulfonyl, alkyl, alkenyl, halo, haloalkyl,
haloalkenyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl,
aminoalkyl, carboalkoxy, carboxy, carboxamido, cyano, and
Q.sup.b;
[0323] B is optionally selected from the group consisting of
hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8
alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of
group B is optionally substituted at any carbon up to and including
6 atoms from the point of attachment of B to A with one or more of
the group consisting of R.sup.32, R.sup.33, R.sup.34, R.sup.35, and
R.sup.36;
[0324] B is optionally a C3-C12 cycloalkyl or a C4-C9 saturated
heterocyclyl, wherein each ring carbon is optionally substituted
with R.sup.33, a ring carbon other than the ring carbon at the
point of attachment of B to A is optionally substituted with oxo
provided that no more than one ring carbon is substituted by oxo at
the same time, ring carbons and a nitrogen adjacent to the carbon
atom at the point of attachment are optionally substituted with
R.sup.9 or R.sup.13, a ring carbon or nitrogen atom adjacent to the
R.sup.9 position and two atoms from the point of attachment is
optionally substituted with R.sup.10, a ring carbon or nitrogen
atom adjacent to the R.sup.13 position and two atoms from the point
of attachment is optionally substituted with R.sup.12, a ring
carbon or nitrogen atom three atoms from the point of attachment
and adjacent to the R.sup.10 position is optionally substituted
with R.sup.11, a ring carbon or nitrogen atom three atoms from the
point of attachment and adjacent to the R.sup.12 position is
optionally substituted with R.sup.33, and a ring carbon or nitrogen
atom four atoms from the point of attachment and adjacent to the
R.sup.11 and R.sup.33 positions is optionally substituted with
R.sup.34;
[0325] R.sup.9, R.sup.10, R.sup.11, R.sup.12, and R.sup.13 are
independently selected from the group consisting of hydrido,
acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl,
amidino, guanidino, alkylenedioxy, haloalkylthio, alkoxy,
cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy,
heteroaralkoxy,heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino,
alkylamino, N-alkyl-N-arylamino, arylamino, aralkylamino,
heteroarylamino, heteroaralkylamino, heterocyclylamino,
heterocyclylalkylamino, alkylthio, alkylsulfinyl, arylsulfinyl,
aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl,
alkylsulfamido, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl,
cycloalkylsulfonyl, heteroarylsulfonyl, amidosulfonyl, alkyl, aryl,
aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl,
halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl,
aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, and
cyano;
[0326] A is bond or (CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr wherein
rr is 0 or 1, pa is an integer selected from 0 through 3, and
W.sup.7 is selected from the group consisting of O, S, C(O),
(R.sup.7)NC(O), (R.sup.7)NC(S), and N(R.sup.7), with the proviso
that W.sup.7 is bonded to the N(H) on the 1,4-quinone ring;
[0327] R.sup.7is selected from the group consisting of hydrido,
hydroxy and alkyl;
[0328] R.sup.15 is selected from the group consisting of hydrido,
hydroxy, halo, alkyl, and haloalkyl;
[0329] X.sup.0 is selected from the group consisting of hydrido,
alkyl, cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl,
alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl,
alkoxyamino, thiol, and alkylthio;
[0330] R.sup.2 is Z.sup.0-Q;
[0331] Z.sup.0 is selected from the group consisting of a bond,
(CR.sup.41R.sup.42).sub.q wherein q is 1 or 2, and
(CH(R.sup.41)).sub.g--W.sup.0--(CH(R.sup.42).sub.p wherein g and p
are integers independently selected from 0 through 3 and W.sup.0 is
selected from the group consisting of O, S, C(O), S(O),
N(R.sup.41), and ON(R.sup.41);
[0332] Z.sup.0 is optionally
(CH(R.sup.41)).sub.e--W.sup.22--(CH(R.sup.42)- ).sub.h wherein e
and h are independently 0 or 1 and W.sup.22 is selected from the
group consisting of CR.sup.41.dbd.CR.sup.42, 1,2-cyclopropyl,
1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl,
1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl,
3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl,
2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,
2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl,
1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,
2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, wherein Z.sup.0
is directly bonded to the 1,4-quinone ring and W.sup.22 is
optionally substituted with one or more substituents selected from
the group consisting of R.sup.9, R.sup.10, R.sup.11, R.sup.12, and
R.sup.13;
[0333] R.sup.41 and R.sup.42 are independently selected from the
group consisting of hydrido, hydroxy, alkyl, and amino;
[0334] Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein
a carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to Z.sup.0 is optionally substituted by
R.sup.9, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.13, a carbon adjacent
to R.sup.9 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.10, a carbon adjacent to
R.sup.13 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.12, and any carbon adjacent to
both R.sup.10 and R.sup.12 is optionally substituted by
R.sup.11;
[0335] Q is optionally hydrido with the proviso that Z.sup.0 is
other than a bond;
[0336] K is CR.sup.4aCr.sup.4b;
[0337] R.sup.4a and R.sup.4b are independently selected from the
group consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl,
alkylthioalkyl, and haloalkyl;
[0338] E.sup.0, with the proviso that K is CR.sup.4aR.sup.4b, is
E.sup.1 wherein E.sup.1 is selected from the group consisting of a
covalent single bond, C(O)N(H), (H)NC(O), S(O).sub.2N(H), and
N(H)S(O).sub.2;
[0339] K is optionally (CH(R.sup.14)).sub.j-T wherein j is 0 or 1
and T is a bond or N(R.sup.7) with the proviso that
(CH(R.sup.14)).sub.j is bonded to the phenyl ring;
[0340] R.sup.14 is hydrido or halo;
[0341] E.sup.0, with the proviso that K is (CH(R.sup.14).sub.j-T,
is E.sup.2 wherein E.sup.2 is selected from the group consisting of
C(O)N(H), (H)NC(O), C(S)N(H), (H)NC(S), S(O).sub.2N(H),
N(H)S(O).sub.2, S(O).sub.2N(H)C(O), and C(O)N(H)S(O).sub.2;
[0342] Y.sup.0 is phenyl or a heteroaryl of 5 or 6 ring members,
wherein one carbon of said phenyl or said heteroaryl is substituted
by Q.sup.s, a carbon two or three atoms from the point of
attachment of Q.sup.s to said phenyl or said heteroaryl is
substituted by Q.sup.b, a carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.17,
another carbon adjacent to the point of attachment of Q.sup.s is
optionally substituted by R.sup.18, a carbon adjacent to Q.sup.b is
optionally substituted by R.sup.16, and another carbon adjacent to
Q.sup.b is optionally substituted by R.sup.19;
[0343] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, amidino, guanidino,
carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino,
alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl,
haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,
aminoalkyl, and cyano;
[0344] R.sup.16 or R.sup.19 is optionally selected from the group
consisting of NR.sup.20R.sup.21,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup- .24), and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido;
[0345] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, hydrido,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24), and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that no more than
one of R.sup.20 and R.sup.21 is selected from the group consisting
of hydroxy, amino, alkylamino, and dialkylamino at the same time,
with the further proviso that no more than one of R.sup.23 and
R.sup.24 is selected from the group consisting of hydroxy, amino,
alkylamino, and dialkylamino at the same time;
[0346] R.sup.20, R.sup.21, R.sup.23, R.sup.24, R.sup.25, and
R.sup.26 are independently selected from the group consisting of
hydrido, alkyl, hydroxy, amino, alkylamino and dialkylamino;
[0347] Q.sup.s is selected from the group consisting of a bond,
(CR.sup.37R.sup.38 ).sub.b wherein b is an integer selected from 1
through 4, and (CH(R.sup.14)).sub.c--W.sup.1--(CH(R.sup.15)).sub.d
wherein c and d are integers independently selected from 1 through
3 and W.sup.1 is selected from the group consisting of
C(O)N(R.sup.14), (R.sup.14)NC(O), S(O), S(O).sub.2,
S(O).sub.2N(R.sup.14), N(R.sup.14)S(O).sub.2, and N(R.sup.14), with
the proviso that R.sup.14 is selected from other than halo when
directly bonded to N, and with the additional proviso that
(CR.sup.37R.sup.38).sub.b and (CR.sup.37R.sup.38).sub.b, and
(CH(R.sup.14)).sub.c are bonded to E.sup.0;
[0348] R.sup.37 and R.sup.38 are independently selected from the
group consisting of hydrido, alkyl, and haloalkyl;
[0349] R.sup.38 is optionally aroyl or heteroaroyl, wherein
R.sup.38 is optionally substituted with one or more substituents
selected from the group consisting of R.sup.16, R.sup.17, R.sup.18,
and R.sup.19;
[0350] Y.sup.0 is optionally Y.sup.AT wherein Y.sup.AT is
Q.sup.b-Q.sup.s;
[0351] Y.sup.0 is optionally Q.sup.b-Q.sup.ss wherein Q.sup.ss is
(CH(R.sup.14)).sub.e--W.sup.2--(CH(R.sup.15)).sub.h, wherein e and
h are independently 1 or 2 and W.sup.2 is CR.sup.4a.dbd.CR.sup.4b
with the proviso that (CH(R.sup.14)).sub.e is bonded to
E.sup.0.
[0352] In an even more preferred embodiment of a compound of
Formula I, said compound is the Formula: 30
[0353] or a pharmaceutically acceptable salt thereof, wherein;
[0354] B is phenyl or a heteroaryl of 5 or 6 ring members, wherein
a carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to A is optionally substituted by
R.sup.32, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.36, a carbon adjacent
to R.sup.32 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.33, a carbon adjacent
to R.sup.36 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.35, and any carbon
adjacent to both R.sup.33 and R.sup.35 is optionally substituted by
R.sup.34;
[0355] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy,
amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl,
halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl,
carboalkoxy, carboxy, carboxamido, cyano, and Q.sup.b;
[0356] A is a bond or (CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr
wherein rr is 0 or 1, pa is an integer selected from 0 through 3,
and W.sup.7 is (R.sup.7)NC(O) or N(R.sup.7);
[0357] R.sup.7 is selected from the group consisting of hydrido,
hydroxy and alkyl;
[0358] R.sup.15 is selected from the group consisting of hydrido,
halo, alkyl, and haloalkyl;
[0359] X.sup.O is selected from the group consisting of hydrido,
hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy,
alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl,
haloalkoxy, and halo;
[0360] R.sup.2 is Z.sup.0-Q;
[0361] Z.sup.0 is selected from the group consisting of a bond,
CH.sub.2, CH.sub.2CH.sub.2, W.sup.0--(CH(R.sup.42)).sub.p wherein p
is 0 or 1 and W.sup.0 is selected from the group consisting of O,
S, and N(R.sup.41);
[0362] R.sup.41 and R.sup.42 are independently hydrido or
alkyl;
[0363] Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein
a carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to Z.sup.0 is optionally substituted by
R.sup.9, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.13, a carbon adjacent
to R.sup.9 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.10, a carbon adjacent to
R.sup.13 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.12, and any carbon adjacent to
both R.sup.10 and R.sup.12 is optionally substituted by
R.sup.11;
[0364] R.sup.9, R.sup.11, and R.sup.13 are independently selected
from the group consisting of hydrido, hydroxy, amino, amidino,
guanidino, alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl,
alkylsulfonyl, amidosulfonyl, alkyl, alkoxy, halo, haloalkyl,
haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboxy, carboxamido,
and cyano;
[0365] R.sup.10 and R.sup.12 are independently selected from the
group consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl,
heteroaryl, heterocyclyl, alkoxy, cycloalkoxy, cycloalkylalkoxy,
aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy,heterocyclyloxy,
heterocyclylalkoxy, hydroxy, amino, alkoxyamino, alkylamino,
arylamino, aralkylamino, heteroarylamino, heteroaralkylamino,
heterocyclylamino, heterocyclylalkylamino, alkylsulfonamido,
amidosulfonyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl,
heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl,
cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl,
hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl,
carboxamido, halo, haloalkyl, and cyano;
[0366] Y.sup.0 is phenyl or a heteroaryl of 5 or 6 ring members,
wherein one carbon of said phenyl or said heteroaryl is substituted
by Q.sup.s, a carbon two or three atoms from the point of
attachment of Q.sup.s to said phenyl or said heteroaryl is
substituted by Q.sup.b, a carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.17,
another carbon adjacent to the point of attachment of Q.sup.s is
optionally substituted by R.sup.18, a carbon adjacent to Q.sup.b is
optionally substituted by R.sup.16, and another carbon adjacent to
Q.sup.b is optionally substituted by R.sup.19;
[0367] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, amidino, guanidino,
carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino,
alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl,
alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and
cyano;
[0368] R.sup.16 or R.sup.19 is optionally NR.sup.20R.sup.21 or
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido;
[0369] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, hydrido, and C(NR.sup.25)NR.sup.23R.sup.24, with
the proviso that no more than one of R.sup.20 and R.sup.21 is
hydroxy at the same time and with the further proviso that no more
than one of R.sup.23 and R.sup.24 is hydroxy at the same time;
[0370] R.sup.20, R.sup.21, R.sup.23, R.sup.24, and R.sup.25 are
independently selected from the group consisting of hydrido, alkyl,
and hydroxy;
[0371] Q.sup.s is selected from the group consisting of a bond,
CH.sub.2, and CH.sub.2CH.sub.2.
[0372] In another even more preferred embodiment of a compound of
Formula I, said compound is the Formula: 31
[0373] or a pharmaceutically acceptable salt thereof, wherein;
[0374] B is selected from the group consisting of hydrido, C2-C8
alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein
each member of group B is optionally substituted at any carbon up
to and including 6 atoms from the point of attachment of B to A
with one or more of the group consisting of R.sup.32, R.sup.33,
R.sup.34, R.sup.35, R.sup.36;
[0375] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy,
amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl,
halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl,
carboalkoxy, carboxy, carboxamido, cyano, and Q.sup.b;
[0376] A is a bond or (CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr
wherein rr is 0 or 1, pa is an integer selected from 0 through 3,
and W.sup.7 is (R.sup.7)NC(O) or N(R.sup.7);
[0377] R.sup.7 is selected from the group consisting of hydrido,
hydroxy and alkyl;
[0378] R.sup.15 is selected from the group consisting of hydrido,
halo, alkyl, and haloalkyl;
[0379] X.sup.O is selected from the group consisting of hydrido,
hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy,
alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl,
haloalkoxy, and halo;
[0380] R.sup.2 is Z.sup.0-Q;
[0381] Z.sup.0 is selected from the group consisting of a bond,
CH.sub.2, CH.sub.2CH.sub.2, W.sup.0--(CH(R.sup.42)).sub.p wherein p
is 0 or 1 and W.sup.0 is selected from the group consisting of O,
S, and N(R.sup.41);
[0382] R.sup.41 and R.sup.42 are independently hydrido or
alkyl;
[0383] Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein
a carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to Z.sup.0 is optionally substituted by
R.sup.9, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.13, a carbon adjacent
to R.sup.9 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.10, a carbon adjacent to
R.sup.13 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.12, and any carbon adjacent to
both R.sup.10 and R.sup.12 is optionally substituted by
R.sup.11;
[0384] R.sup.9, R.sup.11, and R.sup.13 are independently selected
from the group consisting of hydrido, hydroxy, amino, amidino,
guanidino, alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl,
alkylsulfonyl, amidosulfonyl, alkyl, alkoxy, halo, haloalkyl,
haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboxy, carboxamido,
and cyano;
[0385] R.sup.10 and R.sup.12 are independently selected from the
group consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl,
heteroaryl, heterocyclyl, alkoxy, cycloalkoxy, cycloalkylalkoxy,
aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy,heterocyclyloxy,
heterocyclylalkoxy, hydroxy, amino, alkoxyamino, alkylamino,
arylamino, aralkylamino, heteroarylamino, heteroaralkylamino,
heterocyclylamino, heterocyclylalkylamino, alkylsulfonamido,
amidosulfonyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl,
heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl,
cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl,
hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl,
carboxamido, halo, haloalkyl, and cyano;
[0386] Y.sup.0 is phenyl or a heteroaryl of 5 or 6 ring members,
wherein one carbon of said phenyl or said heteroaryl is substituted
by Q.sup.s, a carbon two or three atoms from the point of
attachment of Q.sup.s to said phenyl or said heteroaryl is
substituted by Q.sup.b, a carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.17,
another carbon adjacent to the point of attachment of Q.sup.s is
optionally substituted by R.sup.18, a carbon adjacent to Q.sup.b is
optionally substituted by R.sup.16, and another carbon adjacent to
Q.sup.b is optionally substituted by R.sup.19;
[0387] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, amidino, guanidino,
carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino,
alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl,
alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and
cyano;
[0388] R.sup.16 or R.sup.19 is optionally selected from the group
consisting of NR.sup.20R.sup.21,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup- .24), and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido;
[0389] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, hydrido, C(NR.sup.25)NR.sup.23R.sup.24, and
N(R.sup.26)C(NR.sup.25)N(R.su- p.23)(R.sup.24), with the proviso
that no more than one of R.sup.20 and R.sup.21 is hydroxy at the
same time and with the further proviso that no more than one of
R.sup.23 and R.sup.24 is hydroxy at the same time;
[0390] R.sup.20, R.sup.21, R.sup.23, R.sup.24, R.sup.25, and
R.sup.26 are independently selected from the group consisting of
hydrido, alkyl, and hydroxy;
[0391] Q.sup.s is selected from the group consisting of a bond,
CH.sub.2, and CH.sub.2CH.sub.2.
[0392] In still another even more preferred embodiment of a
compound of Formula I, said compound is the Formula: 32
[0393] or a pharmaceutically acceptable salt thereof, wherein;
[0394] B is a C3-C7 cycloalkyl or a C4-C6 saturated heterocyclyl,
wherein each ring carbon is optionally substituted with R.sup.33, a
ring carbon other than the ring carbon at the point of attachment
of B to A is optionally substituted with oxo provided that no more
than one ring carbon is substituted by oxo at the same time, ring
carbons and a nitrogen adjacent to the carbon atom at the point of
attachment are optionally substituted with R.sup.9 or R.sup.13, a
ring carbon or nitrogen adjacent to the R.sup.9 position and two
atoms from the point of attachment is optionally substituted with
R.sup.10, a ring carbon or nitrogen adjacent to the R.sup.13
position and two atoms from the point of attachment is optionally
substituted with R.sup.12, a ring carbon or nitrogen three atoms
from the point of attachment and adjacent to the R.sup.10 position
is optionally substituted with R.sup.11, a ring carbon or nitrogen
three atoms from the point of attachment and adjacent to the
R.sup.12 position is optionally substituted with R.sup.33, and a
ring carbon or nitrogen four atoms from the point of attachment and
adjacent to the R.sup.11 and R.sup.33 positions is optionally
substituted with R.sup.34;
[0395] R.sup.9, R.sup.11, and R.sup.13 are independently selected
from the group consisting of hydrido, hydroxy, amino, amidino,
guanidino, alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl,
alkylsulfonyl, amidosulfonyl, alkyl, alkoxy, halo, haloalkyl,
haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboxy, carboxamido,
and cyano;
[0396] R.sup.10 and R.sup.12 are independently selected from the
group consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl,
heteroaryl, heterocyclyl, alkoxy, cycloalkoxy, cycloalkylalkoxy,
aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy,heterocyclyloxy,
heterocyclylalkoxy, hydroxy, amino, alkoxyamino, alkylamino,
arylamino, aralkylamino, heteroarylamino, heteroaralkylamino,
heterocyclylamino, heterocyclylalkylamino, alkylsulfonamido,
amidosulfonyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl,
heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl,
cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl,
hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl,
carboxamido, halo, haloalkyl, and cyano;
[0397] R.sup.33 and R.sup.34 are independently selected from the
group consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino,
alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,
hydroxyalkyl, hydroxyhaloalkyl, carboalkoxy, carboxy, carboxamido,
and cyano;
[0398] R.sup.33 is optionally Q.sup.b;
[0399] A is a bond or (CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr
wherein rr is 0 or 1, pa is an integer selected from 0 through 3,
and W.sup.7 is (R.sup.7)NC(O) or N(R.sup.7);
[0400] R.sup.7 is selected from the group consisting of hydrido,
hydroxy and alkyl;
[0401] R.sup.15 is selected from the group consisting of hydrido,
halo, alkyl, and haloalkyl;
[0402] X.sup.O is selected from the group consisting of hydrido,
hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy,
alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl,
haloalkoxy, and halo;
[0403] R.sup.2 is Z.sup.0-Q;
[0404] Z.sup.0 is selected from the group consisting of a bond,
CH.sub.2, CH.sub.2CH.sub.2, W.sup.0--(CH(R.sup.42)).sub.p wherein p
is 0 or 1 and W.sup.0 is selected from the group consisting of O,
S, and N(R.sup.41);
[0405] R.sup.41 and R.sup.42 are independently hydrido or
alkyl;
[0406] Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein
a carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to Z.sup.0 is optionally substituted by
R.sup.9, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.13, a carbon adjacent
to R.sup.9 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.10, a carbon adjacent to
R.sup.13 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.12, and any carbon adjacent to
both R.sup.10 and R.sup.12 is optionally substituted by
R.sup.11;
[0407] Y.sup.0 is phenyl or a heteroaryl of 5 or 6 ring members,
wherein one carbon of said phenyl or said heteroaryl is substituted
by Q.sup.s, a carbon two or three atoms from the point of
attachment of Q.sup.s to said phenyl or said heteroaryl is
substituted by Q.sup.b, a carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.17,
another carbon adjacent to the point of attachment of Q.sup.s is
optionally substituted by R.sup.18, a carbon adjacent to Q.sup.b is
optionally substituted by R.sup.16, and another carbon adjacent to
Q.sup.b is optionally substituted by R.sup.19;
[0408] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, amidino, guanidino,
carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino,
alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl,
alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and
cyano;
[0409] R.sup.16 or R.sup.19 is optionally NR.sup.20R.sup.21 or and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido;
[0410] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, hydrido, and C(NR.sup.25)NR.sup.23R.sup.24, with
the proviso that no more than one of R.sup.20 and R.sup.21 is
hydroxy at the same time and with the further proviso that no more
than one of R.sup.23 and R.sup.24 is hydroxy at the same time;
[0411] R.sup.20, R.sup.21, R.sup.23, R.sup.24, and R.sup.25 are
independently selected from the group consisting of hydrido, alkyl,
and hydroxy;
[0412] Q.sup.s is selected from the group consisting of a bond,
CH.sub.2, and CH.sub.2CH.sub.2.
[0413] In an additional even more preferred embodiment of a
compound of Formula I, said compound is the Formula: 33
[0414] or a pharmaceutically acceptable salt thereof, wherein;
[0415] B is selected from the group consisting of hydrido,
trialkylsilyl, C2-C4 alkyl, C3-C5 alkylenyl, C3-C4 alkenyl, C3-C4
alkynyl, and C2-C4 haloalkyl, wherein each member of group B is
optionally substituted at any carbon up to and including 3 atoms
from the point of attachment of B to A with one or more of the
group consisting of R.sup.32, R.sup.33, and R.sup.34;
[0416] R.sup.32, R.sup.33, and R.sup.34 are independently selected
from the group consisting of hydrido, acetamido, haloacetamido,
amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino,
alkylamino, alkylthio, amidosulfonyl, alkyl, halo, haloalkyl,
haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboalkoxy, carboxy,
carboxamido, and cyano;
[0417] A is (CH(R.sup.15)).sub.pa--N(R.sup.7) wherein pa is an
integer selected from 0 through 2 and R.sup.7 is hydrido or
alkyl;
[0418] R.sup.15 is selected from the group consisting of hydrido,
halo, alkyl, and haloalkyl;
[0419] X.sup.0 is selected from the group consisting of hydrido,
alkyl, cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl,
alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl,
alkoxyamino, thiol, and alkylthio;
[0420] R.sup.2 is Z.sup.0-Q;
[0421] Z.sup.0 is a bond or CH.sub.2;
[0422] Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein
a carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to Z.sup.0 is optionally substituted by
R.sup.9, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.13, a carbon adjacent
to R.sup.9 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.10, a carbon adjacent to
R.sup.13 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.12, and any carbon adjacent to
both R.sup.10 and R.sup.12 is optionally substituted by
R.sup.11;
[0423] R.sup.9, R.sup.11, and R.sup.13 are independently selected
from the group consisting of hydrido, hydroxy, amino, amidino,
guanidino, alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl,
alkylsulfonyl, amidosulfonyl, alkyl, alkoxy, halo, haloalkyl,
haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboxy, carboxamido,
and cyano;
[0424] R.sup.10 and R.sup.12 are independently selected from the
group consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl,
heteroaryl, heterocyclyl, alkoxy, cycloalkoxy, cycloalkylalkoxy,
aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy,
heterocyclylalkoxy, hydroxy, amino, alkoxyamino, alkylamino,
arylamino, aralkylamino, heteroarylamino, heteroaralkylamino,
heterocyclylamino, heterocyclylalkylamino, alkylsulfonamido,
amidosulfonyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl,
heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl,
cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl,
hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl,
carboxamido, halo, haloalkyl, and cyano;
[0425] Y.sup.0 is phenyl or a heteroaryl of 5 or 6 ring members,
wherein one carbon of said phenyl or said heteroaryl is substituted
by Q.sup.s, a carbon two or three atoms from the point of
attachment of Q.sup.s to said phenyl or said heteroaryl is
substituted by Q.sup.b, a carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.17,
another carbon adjacent to the point of attachment of Q.sup.s is
optionally substituted by R.sup.18, a carbon adjacent to Q.sup.b is
optionally substituted by R.sup.16, and another carbon adjacent to
Q.sup.b is optionally substituted by R.sup.19;
[0426] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, amidino, guanidino,
carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino,
alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl,
alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and
cyano;
[0427] R.sup.16 or R.sup.19 is optionally selected from the group
consisting of NR.sup.20R.sup.21,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup- .24), and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido;
[0428] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, hydrido, C(NR.sup.25)NR.sup.23R.sup.24, and
N(R.sup.26)C(NR.sup.25)N(R.su- p.23)(R.sup.24), with the proviso
that no more than one of R.sup.20 and R.sup.21 is hydroxy at the
same time and with the further proviso that no more than one of
R.sup.23 and R.sup.24 is hydroxy at the same time;
[0429] R.sup.20, R.sup.21, R.sup.23, R.sup.24, R.sup.25, and
R.sup.26 are independently selected from the group consisting of
hydrido, alkyl, and hydroxy;
[0430] Q.sup.s is selected from the group consisting of a bond,
CH.sub.2, and CH.sub.2CH.sub.2.
[0431] In a fifth even more preferred embodiment of a compound of
Formula I, said compound is the Formula: 34
[0432] or a pharmaceutically acceptable salt thereof, wherein;
[0433] B is phenyl or a heteroaryl of 5 or 6 ring members, wherein
a carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to A is optionally substituted by
R.sup.32, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.36, a carbon adjacent
to R.sup.32 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.33, a carbon adjacent
to R.sup.36 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.35, and any carbon
adjacent to both R.sup.33 and R.sup.35 is optionally substituted by
R.sup.34;
[0434] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
acetamido, haloacetamido, amidino, guanidino, alkylenedioxy,
haloalkylthio, alkanoyloxy, alkoxy, hydroxy, amino, alkoxyamino,
haloalkanoyl, nitro, alkylamino, alkylthio, aryl, aralkyl,
cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl,
alkylsulfonamido, amidosulfonyl, alkyl, alkenyl, halo, haloalkyl,
haloalkenyl, haloalkoxy, hydroxyalkyl, alkylamino, carboalkoxy,
carboxy, carboxamido, cyano, and Q.sup.b;
[0435] B is optionally selected from the group consisting of
hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8
alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of
group B is optionally substituted at any carbon up to and including
6 atoms from the point of attachment of B to A with one or more of
the group consisting of R.sup.32, R.sup.33, R.sup.34, R.sup.35, and
R.sup.36;
[0436] B is optionally a C3-C12 cycloalkyl or a C4-C9 saturated
heterocyclyl, wherein each ring carbon is optionally substituted
with R.sup.33, a ring carbon other than the ring carbon at the
point of attachment of B to A is optionally substituted with oxo
provided that no more than one ring carbon is substituted by oxo at
the same time, ring carbons and a nitrogen adjacent to the carbon
atom at the point of attachment are optionally substituted with
R.sup.9 or R.sup.13, a ring carbon or nitrogen adjacent to the
R.sup.9 position and two atoms from the point of attachment is
optionally substituted with R.sup.10, a ring carbon or nitrogen
adjacent to the R.sup.13 position and two atoms from the point of
attachment is optionally substituted with R.sup.12, a ring carbon
or nitrogen three atoms from the point of attachment and adjacent
to the R.sup.10 position is optionally substituted with R.sup.11, a
ring carbon or nitrogen three atoms from the point of attachment
and adjacent to the R.sup.12 position is optionally substituted
with R.sup.33, and a ring carbon or nitrogen four atoms from the
point of attachment and adjacent to the R.sup.11 and R.sup.33
positions is optionally substituted with R.sup.34;
[0437] R.sup.9, R.sup.10, R.sup.11, R.sup.12, and R.sup.13 are
independently selected from the group consisting of hydrido,
acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl,
amidino, guanidino, alkylenedioxy, haloalkylthio, alkoxy,
cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy,
heteroaralkoxy,heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino,
alkylamino, N-alkyl-N-arylamino, arylamino, aralkylamino,
heteroarylamino, heteroaralkylamino, heterocyclylamino,
heterocyclylalkylamino, alkylthio, alkylsulfinyl, arylsulfinyl,
aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl,
alkylsulfamido, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl,
cycloalkylsulfonyl, heteroarylsulfonyl, amidosulfonyl, alkyl, aryl,
aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl,
halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl,
aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, and
cyano;
[0438] A is a bond or (CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr
wherein rr is 0 or 1, pa is an integer selected from 0 through 3,
and W.sup.7 is selected from the group consisting of O, S, C(O),
(R.sup.7)NC(O), (R.sup.7)NC(S), and N(R.sup.7);
[0439] R.sup.7 is selected from the group consisting of hydrido,
hydroxy and alkyl;
[0440] R.sup.15 is selected from the group consisting of hydrido,
hydroxy, halo, alkyl, and haloalkyl;
[0441] X.sup.0 is selected from the group consisting of hydrido,
alkyl, cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl,
alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl,
alkoxyamino, thiol, and alkylthio;
[0442] R.sup.2 is Z.sup.0-Q;
[0443] Z.sup.0 is selected from the group consisting of a bond,
(CR.sup.41R.sup.42).sub.q wherein q is 1 or 2, and
(CH(R.sup.41)).sub.g--W.sup.0--(CH(R.sup.42)).sub.p wherein g and p
are integers independently selected from 0 through 3 and W.sup.0 is
selected from the group consisting of O, S, C(O), S(O),
N(R.sup.41), and ON(R.sup.41);
[0444] Z.sup.0 is optionally
(CH(R.sup.41)).sub.e--W.sup.22--(CH(R.sup.42)- ).sub.h wherein e
and h are independently 0 or 1 and W.sup.22 is selected from the
group consisting of CR.sup.41.dbd.CR.sup.42, 1,2-cyclopropyl,
1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl,
1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl,
3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl,
2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,
2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl,
1,2-pyrrolidinyl,1,3-pyrrolidinyl, 2,3-pyrrolidinyl,
2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,
2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,
2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, wherein Z.sup.0
is directly bonded to the 1,4-quinone ring and W.sup.22 is
optionally substituted with one or more substituents selected from
the group consisting of R.sup.9, R.sup.10, R.sup.11, R.sup.12, and
R.sup.13;
[0445] R.sup.41 and R.sup.42 are independently selected from the
group consisting of hydrido, hydroxy, alkyl, and amino;
[0446] Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein
a carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to Z.sup.0 is optionally substituted by
R.sup.9, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.13, a carbon adjacent
to R.sup.9 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.10, a carbon adjacent to
R.sup.13 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.12, and any carbon adjacent to
both R.sup.10 and R.sup.12 is optionally substituted by R.sup.11,
with the proviso that Q is other than a phenyl when Z.sup.0 is a
bond;
[0447] Q is optionally hydrido with the proviso that Z.sup.0 is
selected from other than a bond;
[0448] K is CHR.sup.4a wherein R.sup.4a is selected from the group
consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl,
alkylthioalkyl, and haloalkyl;
[0449] E.sup.0 is selected from the group consisting of a bond,
C(O)N(H), (H)NC(O), (R.sup.7)NS(O).sub.2, and
S(O).sub.2N(R.sup.7);
[0450] Y.sup.AT is Q.sup.b-Q.sup.s;
[0451] Q.sup.s is (CR.sup.37R.sup.38).sub.b wherein b is an integer
selected from 1 through 4, R.sup.37 is selected from the group
consisting of hydrido, alkyl, and haloalkyl, and R.sup.38 is
selected from the group consisting of hydrido, alkyl, haloalkyl,
aroyl, and heteroaroyl with the proviso that there is at least one
aroyl or heteroaroyl substituent, with the further proviso that no
more than one aroyl or heteroaroyl is bonded to
(CR.sup.37R.sup.38).sub.b at the same time, with the still further
proviso that said aroyl and said heteroaroyl are optionally
substituted with one or more substituents selected from the group
consisting of R.sup.16, R.sup.17, R.sup.18, and R.sup.19, with
another further proviso that said aroyl and said heteroaroyl are
bonded to the CR.sup.37R.sup.38 that is directly bonded to E.sup.0,
with still another further proviso that no more than one alkyl or
one haloalkyl is bonded to a CR.sup.37R.sup.38 at the same time,
and with the additional proviso that said alkyl and haloalkyl are
bonded to a carbon other than the one bonding said aroyl or said
heteroaroyl;
[0452] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, amidino, guanidino,
carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino,
alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl,
haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,
aminoalkyl, and cyano;
[0453] R.sup.16 or R.sup.19 is optionally selected from the group
consisting of NR.sup.20R.sup.21,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup- .24), and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido;
[0454] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, hydrido,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24), and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that no more than
one of R.sup.20 and R.sup.21 is selected from the group consisting
of hydroxy, amino, alkylamino, and dialkylamino at the same time
and with the further proviso that no more than one of R.sup.23 and
R.sup.24 is selected from the group consisting of hydroxy, amino,
alkylamino, and dialkylamino at the same time;
[0455] R.sup.20, R.sup.21, R.sup.23, R.sup.24, R.sup.25, and
R.sup.26 are independently selected from the group consisting of
hydrido, alkyl, hydroxy, amino, alkylamino and dialkylamino.
[0456] In a most preferred embodiment of compounds of Formula I,
said compound is the formula: 35
[0457] or a pharmaceutically acceptable salt thereof, wherein;
[0458] B is phenyl or a heteroaryl of 5 or 6 ring members, wherein
a carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to A is optionally substituted by
R.sup.32, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.36, a carbon adjacent
to R.sup.32 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.33, a carbon adjacent
to R.sup.36 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.35, and any carbon
adjacent to both R.sup.33 and R.sup.35 is optionally substituted by
R.sup.34;
[0459] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy,
amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl,
halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy,
carboxamido, cyano, and Q.sup.b;
[0460] A is a bond or (CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr
wherein rr is 0 or 1, pa is an integer selected from 0 through 3,
and W.sup.7 is N(R.sup.7);
[0461] R.sup.7 is hydrido or alkyl; .sup.R.sup.15 is selected from
the group consisting of hydrido, halo, alkyl, and haloalkyl;
[0462] X.sup.O is selected from the group consisting of hydrido,
hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy,
alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl,
haloalkoxy, and halo;
[0463] R.sup.2 is Z.sup.0-Q;
[0464] Z.sup.0 is a bond;
[0465] Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein
a carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to Z.sup.0 is optionally substituted by
R.sup.9, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.13, a carbon adjacent
to R.sup.9 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.10, a carbon adjacent to
R.sup.13 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.12, and any carbon adjacent to
both R.sup.10 and R.sup.12 is optionally substituted by
R.sup.11;
[0466] R.sup.9, R.sup.11, and R.sup.13 are independently selected
from the group consisting of hydrido, hydroxy, amino, amidino,
guanidino, alkylamino, alkylthio, alkoxy, alkylsulfinyl,
alkylsulfonyl, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,
hydroxyalkyl, carboxy, carboxamido, and cyano;
[0467] R.sup.10 and R.sup.12 are independently selected from the
group consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkyl, alkoxy, alkoxyamino, hydroxy, amino, alkylamino,
alkylsulfonamido, amidosulfonyl, hydroxyalkyl, aminoalkyl, halo,
haloalkyl, carboalkoxy, carboxy, carboxamido, carboxyalkyl, and
cyano;
[0468] Y.sup.0 is phenyl or a heteroaryl of 5 or 6 ring members,
wherein one carbon of said phenyl or said heteroaryl is substituted
by Q.sup.s, a carbon two or three atoms from the point of
attachment of Q.sup.s to said phenyl or said heteroaryl is
substituted by Q.sup.b, a carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.17,
another carbon adjacent to the point of attachment of Q.sup.s is
optionally substituted by R.sup.18, a carbon adjacent to Q.sup.b is
optionally substituted by R.sup.16, and another carbon adjacent to
Q.sup.b is optionally substituted by R.sup.19;
[0469] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, amidino, guanidino,
carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino,
alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl,
alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and
cyano;
[0470] R.sup.16 or R.sup.19 is optionally NR.sup.20R.sup.21 or
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido;
[0471] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, hydrido, and C(NR.sup.25)NR.sup.23R.sup.24;
[0472] R.sup.20, R.sup.21, R.sup.23, R.sup.24, and R.sup.25 are
independently hydrido or alkyl; Q.sup.s is CH.sub.2.
[0473] In a further most preferred embodiment of compounds of
Formula I, said compound is the formula: 36
[0474] or a pharmaceutically acceptable salt thereof, wherein;
[0475] B is selected from the group consisting of hydrido, C2-C8
alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein
each member of group B is optionally substituted at any carbon up
to and including 6 atoms from the point of attachment of B to A
with one or more of the group consisting of R.sup.32, R.sup.33,
R.sup.34, R.sup.35, and R.sup.36;
[0476] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy,
amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl,
halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy,
carboxamido, cyano, and Q.sup.b;
[0477] A is a bond or (CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr
wherein rr is 0 or 1, pa is an integer selected from 6 through 3,
and W.sup.7 is N(R.sup.7);
[0478] R.sup.7 is hydrido or alkyl;
[0479] R.sup.15 is selected from the group consisting of hydrido,
halo, alkyl, and haloalkyl;
[0480] X.sup.O is selected from the group consisting of hydrido,
hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy,
alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl,
haloalkoxy, and halo;
[0481] R.sup.2 is Z.sup.0-Q;
[0482] Z.sup.0 is a bond;
[0483] Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein
a carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to Z.sup.0 is optionally substituted by
R.sup.9, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.13, a carbon adjacent
to R.sup.9 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.10, a carbon adjacent to
R.sup.13 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.12, and any carbon adjacent to
both R.sup.10 and R.sup.12 is optionally substituted by
R.sup.11;
[0484] R.sup.9, R.sup.11, and R.sup.13 are independently selected
from the group consisting of hydrido, hydroxy, amino, amidino,
guanidino, alkylamino, alkylthio, alkoxy, alkylsulfinyl,
alkylsulfonyl, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,
hydroxyalkyl, carboxy, carboxamido, and cyano;
[0485] R.sup.10 and R.sup.12 are independently selected from the
group consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkyl, alkoxy, alkoxyamino, hydroxy, amino, alkylamino,
alkylsulfonamido, amidosulfonyl, hydroxyalkyl, aminoalkyl, halo,
haloalkyl, carboalkoxy, carboxy, carboxamido, carboxyalkyl, and
cyano;
[0486] Y.sup.0 is phenyl or a heteroaryl of 5 or 6 ring members,
wherein one carbon of said phenyl or said heteroaryl is substituted
by Q.sup.s, a carbon two or three atoms from the point of
attachment of Q.sup.s to said phenyl or said heteroaryl is
substituted by Q.sup.b, a carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.17,
another carbon adjacent to the point of attachment of Q.sup.s is
optionally substituted by R.sup.18, a carbon adjacent to Q.sup.b is
optionally substituted by R.sup.16, and another carbon adjacent to
Q.sup.b is optionally substituted by R.sup.19;
[0487] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, amidino, guanidino,
carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino,
alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl,
alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and
cyano;
[0488] R.sup.16 or R.sup.19 is optionally selected from the group
consisting of NR.sup.20R.sup.21,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup- .24) and
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido;
[0489] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, hydrido,
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24), and
C(NR.sup.25)NR.sup.23R.sup.24;
[0490] R.sup.20, R.sup.21, R.sup.23, R.sup.24, R.sup.25, and
R.sup.26 are independently hydrido or alkyl;
[0491] Q.sup.s is CH.sub.2.
[0492] In a still further most preferred embodiment of compounds of
Formula I, said compound is the formula: 37
[0493] or a pharmaceutically acceptable salt thereof, wherein;
[0494] B is a C3-C7 cycloalkyl or a C4C6 saturated heterocyclyl,
wherein each ring carbon is optionally substituted with R.sup.33, a
ring carbon other than the ring carbon at the point of attachment
of B to A is optionally substituted with oxo provided that no more
than one ring carbon is substituted by oxo at the same time, ring
carbons and a nitrogen adjacent to the carbon atom at the point of
attachment are optionally substituted with R.sup.9 or R.sup.13, a
ring carbon or nitrogen adjacent to the R.sup.9 position and two
atoms from the point of attachment is optionally substituted with
R.sup.10, a ring carbon or nitrogen adjacent to the R.sup.13
position and two atoms from the point of attachment is optionally
substituted with R.sup.12, a ring carbon or nitrogen three atoms
from the point of attachment and adjacent to the R.sup.10 position
is optionally substituted with R.sup.11, a ring carbon or nitrogen
three atoms from the point of attachment and adjacent to the
R.sup.12 position is optionally substituted with R.sup.33, and a
ring carbon or nitrogen four atoms from the point of attachment and
adjacent to the R.sup.11 and R.sup.33 positions is optionally
substituted with R.sup.34;
[0495] R.sup.9, R.sup.11, and R.sup.13 are independently selected
from the group consisting of hydrido, hydroxy, amino, amidino,
guanidino, alkylamino, alkylthio, alkoxy, alkylsulfinyl,
alkylsulfonyl, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,
hydroxyalkyl, carboxy, carboxamido, and cyano;
[0496] R.sup.10 and R.sup.12 are independently selected from the
group consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkyl, alkoxy, alkoxyamino, hydroxy, amino, alkylamino,
alkylsulfonamido, amidosulfonyl, hydroxyalkyl, aminoalkyl, halo,
haloalkyl, carboalkoxy, carboxy, carboxamido, carboxyalkyl, and
cyano;
[0497] R.sup.33 and R.sup.34 are independently selected from the
group consisting of hydrido, acetamido, haloacetamido, amidino,
guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino,
alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,
hydroxyalkyl, carboalkoxy, carboxy, carboxamido, and cyano;
[0498] R.sup.33 is optionally Q.sup.b;
[0499] A is a bond or (CH(R.sup.15)).sub.pa--(W.sup.7).sub.rr
wherein rr is 0 or 1, pa is an integer selected from 0 through 3,
and W.sup.7 is N(R.sup.7);
[0500] R.sup.7 is hydrido or alkyl;
[0501] R.sup.15 is selected from the group consisting of hydrido,
halo, alkyl, and haloalkyl;
[0502] X.sup.O is selected from the group consisting of hydrido,
hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy,
alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl,
haloalkoxy, and halo;
[0503] R.sup.2 is Z.sup.0-Q;
[0504] Z.sup.0 is a bond;
[0505] Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein
a carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to Z.sup.0 is optionally substituted by
R.sup.9, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.13, a carbon adjacent
to R.sup.9 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.10, a carbon adjacent to
R.sup.13 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.12, and any carbon adjacent to
both R.sup.10 and R.sup.12 is optionally substituted by
R.sup.11;
[0506] Y.sup.0 is phenyl or a heteroaryl of 5 or 6 ring members,
wherein one carbon of said phenyl or said heteroaryl is substituted
by Q.sup.s, a carbon two or three atoms from the point of
attachment of Q.sup.s to said phenyl or said heteroaryl is
substituted by Q.sup.b, a carbon adjacent to the point of
attachment of Q.sup.s is optionally substituted by R.sup.17,
another carbon adjacent to the point of attachment of Q.sup.s is
optionally substituted by R.sup.18, a carbon adjacent to Q.sup.b is
optionally substituted by R.sup.16, and another carbon adjacent to
Q.sup.b is optionally substituted by R.sup.19;
[0507] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, amidino, guanidino,
carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino,
alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl,
alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and
cyano;
[0508] R.sup.16 or R.sup.19 is optionally NR.sup.20R.sup.21 or
C(NR.sup.25)NR.sup.23R.sup.24, with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido;
[0509] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, hydrido, and C(NR.sup.25)NR.sup.23R.sup.24;
[0510] R.sup.20, R.sup.21, R.sup.23, R.sup.24, and R.sup.25 are
independently hydrido or alkyl; Q.sup.s is CH.sub.2.
[0511] In a preferred specific embodiment of Formula 1, compounds
have the formula: 38
[0512] or a pharmaceutically acceptable salt thereof, wherein;
[0513] B is selected from the group consisting of phenyl,
2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,
2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl,
1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,2,4-oxadiazol-3-yl,
1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl,
3-isothiazolyl, 5-isothiazolyl, 2-oxazolyl, 2-thiazolyl,
3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,
2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl,
3-pyridazinyl, 4-pyridazinyl, 1,3,5-triazin-2-yl,
1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazinyl,
1,2,3-triazinyl, and 1,2,3-triazin-5-yl, wherein a carbon adjacent
to the carbon at the point of attachment is optionally substituted
by R.sup.32, the other carbon adjacent to the carbon at the point
of attachment is optionally substituted by R.sup.36, a carbon
adjacent to R.sup.32 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.33, a carbon adjacent
to R.sup.36 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.35, and any carbon
adjacent to both R.sup.33 and R.sup.35 is optionally substituted by
R.sup.34;
[0514] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, methyl, ethyl, isopropyl, propyl,
methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino,
ethoxyamino, acetamido, trifluoroacetamido, nitro, aminomethyl,
1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,
N-ethylamino, methylthio, ethylthio, isopropylthio,
trifluoromethylthio, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,
acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
2,2,2-trifluoro-1-hydroxyethyl,
2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl,
methoxycarbonyl,ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and
Q.sup.b;
[0515] B is selected from the group consisting of hydrido,
trimethylsilyl, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl,
butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, tert-butyl,
isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl,
4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 1-methyl-2-butenyl,
1-methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl,
1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl,
2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl,
3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl,
3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl,
2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl,
1-methyl-4-pentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl,
3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl,
1-ethyl-2-butynyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl,
5-heptenyl, 6-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl,
5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl,
1-methyl-4-hexenyl, 1-methyl-5-hexenyl, 1-methyl-2-hexynyl,
1-methyl-3-hexynyl, 1-methyl-4-hexynyl, 3-heptyl,
1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl,
1-butyl-2-propenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl,
1-octyl, 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl,
7-octenyl, 2-octynyl, 3-octynyl, 4-octynyl, 5-octynyl, 6-octynyl,
2-octyl, 1-methyl-2-heptenyl, 1-methyl-3-heptenyl,
1-methyl-4-heptenyl, 1-methyl-5-heptenyl, 1-methyl-6-heptenyl,
1-methyl-2-heptynyl, 1-methyl-3-heptynyl, 1-methyl-4-heptenyl,
1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-2-heptenyl,
1-methyl-3-heptynyl, 1-methyl-4-heptynyl, 1-methyl-5-heptynyl,
3-octyl, 1-ethyl-2-hexenyl, 1-ethyl-3-hexenyl, 1-ethyl-4-hexenyl,
1-ethyl-2-hexynyl, 1-ethyl-3-hexynyl, 1-ethyl-4-hexynyl,
1-ethyl-5-hexenyl, 1-pentyl-2-propenyl, 4-octyl,
1-propyl-2-pentenyl, 1-propyl-3-pentenyl, 1-propyl-4-pentenyl,
1-butyl-2-butenyl, 1-propyl-2-pentynyl, 1-propyl-3-pentynyl,
1-butyl-2-butynyl, 1-butyl-3-butenyl, 2,2,2-trifluoroethyl,
2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluo- ropentyl,
4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and
3,3,3-trifluoropropyl, wherein each member of group B is optionally
substituted at any carbon up to and including 5 atoms from the
point of attachment of B to A with one or more of the group
consisting of R.sup.32, R.sup.33, R.sup.34, R.sup.35, and
R.sup.36;
[0516] B is optionally selected from the group consisting of
cyclopropyl, cyclobutyl, oxetan-2-yl, oxetan-3-yl, azetidin-1-yl,
azetidin-2-yl, azetidin-3-yl, thiaetan-2-yl, thiaetan-3-yl,
cyclopentyl, cyclohexyl, adamantyl, norbornyl,
3-trifluoromethylnorbornyl, 7-oxabicyclo[2.2.1]hept- an-2-yl,
bicyclo[3.1.0]hexan-6-yl, cycloheptyl, cyclooctyl, 2-morpholinyl,
3-morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piperazinyl,
1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl,
1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl,
4H-2-pyranyl, 4H-3-pyranyl, 4H-4-pyranyl, 4H-pyran-4-one-2-yl,
4H-pyranone-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl,
2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl,
2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring
carbon is optionally substituted with R.sup.33, a ring carbon and
nitrogen atoms adjacent to the carbon atom at the point of
attachment is optionally substituted with R.sup.9 or R.sup.13, a
ring carbon or nitrogen atom adjacent to the R.sup.9 position and
two atoms from the point of attachment is optionally substituted
with R.sup.10, and a ring carbon or nitrogen atom adjacent to the
R.sup.13 position and two atoms from the point of attachment is
optionally substituted with R.sup.12;
[0517] R.sup.9, R.sup.10, R.sup.11, R.sup.12, and R.sup.13 are
independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl, propyl,
isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,
methoxyamino, ethoxyamino, acetamido, trifluoroacetamnido,
aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,
dimethylamino, N-ethylamino, methanesulfonamido, amidosulfonyl,
N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,
methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl,
N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl,
N-(3-fluorobenzyl)amidocarbonyl,
N-(2-trifluoromethylbenzyl)amidocarbonyl- ,
N-(1-phenylethyl)amidocarbonyl,
N-(1-methyl-1-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl,
N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl,
N-isopropylamidocarbonyl, N-propylamidocarbonyl,
N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,
N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl,
N-cyclohexylamidocarbonyl, fluoro, chloro, bromo, cyano,
cyclobutoxy, cyclohexoxy, cyclohexylmethoxy,
4-trifluoromethycyclohexylmethoxy, cyclopentoxy, benzyl, benzyloxy,
4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy,
4-bromobenzylamino, 5-bromopyrid-2-ylmethylamino,
4-butoxyphenamino, 3-chlorobenzyl, 4-chlorophenoxy,
4-chloro-3-ethylphenoxy, 4-chloro-3-ethylbenzylamino,
4-chloro-3-ethylphenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy,
4-chlorobenzylsulfonyl, 4-chlorophenylamino,
4-chlorophenylsulfonyl, 5-chloropyrid-3-yloxy,
2-cyanopyrid-3-yloxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy,
3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorophenoxy,
3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy,
2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy,
3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyloxy,
3,5-dimethylbenzyloxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy,
3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy,
4-fluorobenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy,
3-fluoro-5-trifluoromethylbenzyloxy,
4-fluoro-2-trifluoromethylbenzyloxy,
4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy,
4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy,
2-fluorobenzyloxy, 4-fluorophenylamino,
2-fluorotrifluoromethylphenoxy, 4-isopropylbenzyloxy,
3-isopropylphenoxy, 4-isopropylphenoxy,
4-isopropyl-3-methylphenoxy, 4-isopropylbenzyloxy,
3-isopropylphenoxy, 4-isopropylphenoxy,
4-isopropyl-3-methylphenoxy, phenylamino, 1-phenylethoxy,
2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino, phenylsulfonyl,
3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy,
3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy,
3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy,
2,4-bis-trifluoromethylbenzyloxy, 3-trifluoromethylbenzyl,
3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy,
3-trifluoromethylphenoxy, 3-trifluoromethylthiobenzyloxy,
4-trifluoromethylthiobenzyloxy, 2,3,4-trifluorophenoxy,
2,3,5-trifluorophenoxy, 3-pentafluoroethylphenoxy,
3-(1,1,2,2-tetrafluoroethoxy)phenoxy, and
3-trifluoromethylthiophenoxy;
[0518] A is selected from the group consisting of a bond, O, S, NH,
N(CH.sub.3), N(OH), C(O), CH.sub.2, CH.sub.3CH, CF.sub.3CH, NHC(O),
N(CH.sub.3)C(O), C(O)NH, C(O)N(CH.sub.3), CF.sub.3CC(O),
C(O)CCH.sub.3, C(O)CCF.sub.3, CH.sub.2C(O), (O)CCH.sub.2,
CH.sub.2CH.sub.2, CH.sub.2CH.sub.2CH.sub.2, CH.sub.3CHCH.sub.2,
CF3CHCH.sub.2, CH.sub.3CC(O)CH.sub.2, CF.sub.3CC(O)CH.sub.2,
CH.sub.2C(O)CCH.sub.3, CH.sub.2C(O)CCF.sub.3, CH.sub.2CH.sub.2C(O),
and CH.sub.2(O)CCH.sub.2;
[0519] A is optionally selected from the group consisting of
CH.sub.2N(CH.sub.3), CH.sub.2N(CH.sub.2CH.sub.3),
CH.sub.2CH.sub.2N(CH.su- b.3), and
CH.sub.2CH.sub.2N(CH.sub.2CH.sub.3) with the proviso that B is
hydrido;
[0520] X.sup.O is selected from the group consisting of hydrido,
hydroxy, amino, thiol, amidino, hydroxyamino, aminomethyl,
1-aminoethyl, 2-aminoethyl, methylamino, dimethylamino, cyano,
methyl, ethyl, isopropyl, propyl, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, methoxy, ethoxy, propoxy,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino,
ethoxyamino, methylthio, ethylthio, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo;
[0521] R.sup.2 is Z.sup.0-Q;
[0522] Z.sup.0 is selected from the group consisting of a bond,
CH.sub.2, CH.sub.2CH.sub.2, O, S, NH, N(CH.sub.3), CH(OH),
OCH.sub.2, SCH.sub.2, N(H)CH.sub.2, CH.sub.2O, CH.sub.2S,
CH.sub.2N(H), CH(NH.sub.2), CH.sub.2CH(OH), CH.sub.2CHNH.sub.2,
CH(OH)CH.sub.2, and CH(NH.sub.2)CH.sub.2;
[0523] Q is selected from the group consisting of phenyl,
2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,
2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl,
1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,2,4-oxadiazol-3-yl,
1,2,4-oxadiazol-yl, 1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl,
3-isothiazolyl, 5-isothiazolyl, 2-oxazolyl, 2-thiazolyl,
3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,
2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl,
3-pyridazinyl, 4-pyridazinyl, 1,3,5-triazin-2-yl,
1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl,
1,2,3-triazinyl, and 1,2,3-triazin-5-yl, wherein a carbon adjacent
to the carbon at the point of attachment is optionally substituted
by R.sup.9, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.13, a carbon adjacent
to R.sup.9 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.10, a carbon adjacent to
R.sup.13 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.12, and any carbon adjacent to
both R.sup.10 and R.sup.12 is optionally substituted by
R.sup.11;
[0524] K is CR.sup.4aR.sup.4b wherein R.sup.4a and R.sup.4b are
independently selected from the group consisting of methyl, ethyl,
propyl, isopropyl, fluoro, chloro, hydroxy, hydroxymethyl,
1-hydroxyethyl, methoxymethyl, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoromethyl, methylthiomethyl, and hydrido;
[0525] E.sup.0 is a bond, C(O)N(H), (H)NC(O), and
S(O).sub.2N(H);
[0526] Y.sup.0 is selected from the group of formulas consisting
of: 394041
[0527] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, methyl, ethyl,
isopropyl, propyl, amidino, guanidino, carboxy, methoxy, ethoxy,
isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,
aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N-methylamino,
dimethylamino, N-ethylamino; methylthio, ethythio, isopropylthio,
trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,
ethylsulfonyl, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,
trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,
acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl,
hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, and cyano;
[0528] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, hydrido, C(NR.sup.25)NR.sup.23R.sup.24 and
N(R.sup.26)C(NR.sup.25)N(R.sup- .23)(R.sup.24), with the proviso
that no more than one of R.sup.20 and R.sup.21 is hydroxy,
N-methylamino, and N,N-dimethylamino at the same time and that no
more than one of R.sup.23 and R.sup.24 is hydroxy, N-methylamino,
and N,N-dimethylamino at the same time;
[0529] R.sup.20, R.sup.21, R.sup.23, R.sup.24, R.sup.25, and
R.sup.26 are independently selected from the group consisting of
hydrido, methyl, ethyl, propyl, butyl, isopropyl, hydroxy,
2-aminoethyl, 2-(N-methylamino)ethyl, and
2-(N,N-dimethylamino)ethyl;
[0530] Q.sup.s is selected from the group consisting of a bond,
CH.sub.2, CH.sub.2CH.sub.2, CH.sub.3CH, CF.sub.3CH,
CH.sub.3CHCH.sub.2, CF.sub.3CHCH.sub.2, CH.sub.2(CH.sub.3)CH,
CH.dbd.CH, CF.dbd.CH, C(CH.sub.3).dbd.CH, CH.dbd.CHCH.sub.2,
CF.dbd.CHCH.sub.2, C(CH.sub.3).dbd.CHCH.sub.2, CH.sub.2CH.dbd.CH,
CH.sub.2CF.dbd.CH, CH.sub.2C(CH.sub.3).dbd.CH,
CH.sub.2CH.dbd.CHCH.sub.2, CH.sub.2CF.dbd.CHCH.sub.2,
CH.sub.2C(CH.sub.3).dbd.CHCH.sub.2,
CH.sub.2CH.dbd.CHCH.sub.2CH.sub.2,
CH.sub.2CF.dbd.CHCH.sub.2CH.sub.2, and
CH.sub.2C(CH.sub.3).dbd.CHCH.sub.2CH.sub.2.
[0531] In a more preferred specific embodiment of Formula 1,
compounds have the formula: 42
[0532] or a pharmaceutically acceptable salt thereof, wherein;
[0533] B is selected from the group consisting of phenyl,
2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,
2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl,
3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,
2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl,
3-pyridazinyl, 4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a
carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to A is optionally substituted by
R.sup.32, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.36, a carbon adjacent
to R.sup.32 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.33, a carbon adjacent
to R.sup.36 and two atoms from the carbon at the point of
attachment is optionally substituted by R.sup.35, and any carbon
adjacent to both R.sup.33 and R.sup.35 is optionally substituted by
R.sup.34;
[0534] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy,
hydroxy, amino, methoxyamino, ethoxyamino, acetamido,
trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino,
methylthio, ethylthio, isopropylthio, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,
N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,
methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and
Q.sup.b;
[0535] A is selected from the group consisting of a bond, NH,
N(CH.sub.3), N(OH), CH.sub.2, CH.sub.3CH, CF.sub.3CH, NHC(O),
N(CH.sub.3)C(O), C(O)NH, C(O)N(CH.sub.3), CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2, CH.sub.3CHCH.sub.2, and
CF.sub.3CHCH.sub.2;
[0536] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, methyl, ethyl,
isopropyl, propyl, carboxy, amidino, guanidino, methoxy, ethoxy,
isopropoxy, propoxy, hydroxy, amino, aminomethyl, 1-aminoethyl,
2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino,
methylthio, ethylthio, isopropylthio, trifluoromethylthio,
methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, and cyano;
[0537] R.sup.16 or R.sup.19 is optionally
C(NR.sup.25)NR.sup.23R.sup.24 with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido;
[0538] Q.sup.b is C(NR.sup.25)NR.sup.23R.sup.24 or hydrido, with
the proviso that no more than one of R.sup.23 and R.sup.24 is
hydroxy at the same time;
[0539] R.sup.23, R.sup.24, and R.sup.25 are independently selected
from the group consisting of hydrido, methyl, ethyl, and
hydroxy.
[0540] In another more preferred specific embodiment of Formula I,
compounds have the formula: 43
[0541] or a pharmaceutically acceptable salt thereof, wherein;
[0542] B is selected from the group consisting of hydrido, ethyl,
2-propynyl, 2-propenyl, propyl, isopropyl, butyl, 2-butenyl,
3-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl,
2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl,
2-pentynyl, 3-pentynyl, 2-pentyl, 1-methyl-2-butenyl,
1-methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl,
1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl,
2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl,
3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl,
3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl,
2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl,
1-methylpentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl,
3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 1-propyl-2-propenyl,
1-ethyl-2-butynyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl,
5-heptenyl, 6-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl,
5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl,
1-methylthexenyl, 1-methyl-5-hexenyl, 1-methyl-2-hexynyl,
1-methyl-3-hexynyl, 1-methyl-4-hexynyl, 3-heptyl,
1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethylpentenyl,
1-butyl-2-propenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl,
2,2,2-trifluoroethyl, 2,2-difluoropropyl,
4-trifluoromethyl-5,5,trifluoro- pentyl, 4-trifluoromethylpentyl,
5,5,6,6,-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein each
member of group B is optionally substituted at any carbon up to and
including 5 atoms from the point of attachment of B to A with one
or more of the group consisting of R.sup.32, R.sup.33, R.sup.34,
R.sup.35, and R.sup.36;
[0543] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy,
hydroxy, amino, methoxyamino, ethoxyamino, acetamido,
trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino,
methylthio, ethylthio, isopropylthio, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,
N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,
methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and
Q.sup.b;
[0544] A is selected from the group consisting of bond, NH,
N(CH.sub.3), N(OH), CH.sub.2, CH.sub.3CH, CF.sub.3CH, NHC(O),
N(CH.sub.3)C(O), C(O)NH, C(O)N(CH.sub.3), CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2, CH.sub.3CHCH.sub.2, and
CF.sub.3CHCH.sub.2;
[0545] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, methyl, ethyl,
isopropyl, propyl, carboxy, amidino, guanidino, methoxy, ethoxy,
isopropoxy, propoxy, hydroxy, amino, aminomethyl, 1-aminoethyl,
2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino,
methylthio, ethylthio, isopropylthio, trifluoromethylthio,
methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, and cyano;
[0546] R.sup.16 or R.sup.19 is optionally selected from the group
consisting of NR.sup.20R.sup.21, C(NR.sup.25)NR.sup.23R.sup.24, and
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.sup.24), with the proviso that
R.sup.16, R.sup.19, and Q.sup.b are not simultaneously hydrido;
[0547] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, hydrido, C(NR.sup.25)NR.sup.23R.sup.24, and
N(R.sup.26)C(NR.sup.25)N(R.su- p.23)(R.sup.24), with the proviso
that no more than one of R.sup.20 and R.sup.21 is hydroxy at the
same time and with the further proviso that no more than one of
R.sup.23 and R.sup.24 is hydroxy at the same time;
[0548] R.sup.20, R.sup.21, R.sup.23, R.sup.24, R.sup.25, and
R.sup.26 are independently selected from the group consisting of
hydrido, methyl, ethyl, propyl, butyl, isopropyl, and hydroxy.
[0549] In still another more preferred specific embodiment of
Formula 1, compounds have the formula: 44
[0550] or a pharmaceutically acceptable salt thereof, wherein;
[0551] B is selected from the group consisting of cyclopropyl,
cyclobutyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl,
azetidin-3-yl, thiaetan-3-yl, cyclopentyl, cyclohexyl, norbornyl,
7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl,
cycloheptyl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl,
1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl,
3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl,
3-pyrrolidinyl, 2-dioxanyl, 4H-2-pyranyl, 4H-3-pyranyl,
4H4-pyranyl, 4H-pyranone-2-yl, 4H-pyran-4-one-3-yl,
2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl,
3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and
3-tetrahydrothienyl, wherein each ring carbon is optionally
substituted with R.sup.33, ring carbons and a nitrogen adjacent to
the carbon atom at the point of attachment are optionally
substituted with R.sup.9 or R.sup.13, a ring carbon or nitrogen
adjacent to the R.sup.9 position and two atoms from the point of
attachment is optionally substituted with R.sup.10, and a ring
carbon or nitrogen adjacent to the R.sup.13 position and two atoms
from the point of attachment is optionally substituted with
R.sup.12;
[0552] R.sup.33 is selected from the group consisting of hydrido,
amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy,
hydroxy, amino, methoxyamino, ethoxyamino, acetamido,
trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino,
methylthio, ethylthio, isopropylthio, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,
N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,
methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and
Q.sup.b;
[0553] A is selected from the group consisting of a bond, NH,
N(CH.sub.3), N(OH), CH.sub.2, CH.sub.3CH, CF.sub.3CH, NHC(O),
N(CH.sub.3)C(O), C(O)NH, C(O)N(CH.sub.3), CH.sub.2CH.sub.2,
CH.sub.2CH.sub.2CH.sub.2, CH.sub.3CHCH.sub.2, and
CF.sub.3CHCH.sub.2;
[0554] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, methyl, ethyl,
isopropyl, propyl, carboxy, amidino, guanidino, methoxy, ethoxy,
isopropoxy, propoxy, hydroxy, amino, aminomethyl, 1-aminoethyl,
2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino,
methylthio, ethylthio, isopropylthio, trifluoromethylthio,
methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, and cyano;
[0555] R.sup.16 or R.sup.19 is optionally
C(NR.sup.25)NR.sup.23R.sup.24 with the proviso that R.sup.16,
R.sup.19, and Q.sup.b are not simultaneously hydrido;
[0556] Q.sup.b is C(NR.sup.25 )NR.sup.23R.sup.24 or hydrido, with
the proviso that no more than one of R.sup.23 and R.sup.24 is
hydroxy at the same time;
[0557] R.sup.23, R.sup.24, and R.sup.25 are independently selected
from the group consisting of hydrido, methyl, ethyl, and
hydroxy.
[0558] The more preferred specific embodiment compounds of Formula
I having the formula: 45
[0559] or a pharmaceutically acceptable salt thereof, have common
structural units, wherein;
[0560] X.sup.O is selected from the group consisting of hydrido,
hydroxy, amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl,
methylamino, dimethylamino, cyano, methyl, ethyl, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy, hydroxymethyl,
1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio,
ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro,
chloro, and bromo;
[0561] R.sup.2 is Z.sup.0-Q;
[0562] Z.sup.0 is selected from the group consisting of a bond,
CH.sub.2, CH.sub.2CH.sub.2, O, S, NH, N(CH.sub.3), OCH.sub.2,
SCH.sub.2, N(H)CH.sub.2, and N(CH.sub.3)CH.sub.2;
[0563] Q is selected from the group consisting of phenyl,
2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,
2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl,
3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,
2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl,
3-pyridazinyl, 4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a
carbon adjacent to the carbon at the point of attachment of said
phenyl or heteroaryl ring to Z.sup.0 is optionally substituted by
R.sup.9, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.13, a carbon adjacent
to R.sup.9 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.10, a carbon adjacent to
R.sup.13 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.12, and any carbon adjacent to
both R.sup.10 and R.sup.12 is optionally substituted by
R.sup.11;
[0564] R.sup.9, R.sup.11, and R.sup.13 are independently selected
from the group consisting of hydrido, amidino, guanidino, carboxy,
methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy,
propoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino,
N-ethylamino, methylthio, ethylthio, isopropylthio,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,
2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,
1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,
methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl,
N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,
2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl,
N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;
[0565] R.sup.10 and R.sup.12 are independently selected from the
group consisting of hydrido, amidino, guanidino, carboxy,
carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy,
isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,
acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl,
2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino,
methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl,
N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,
2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl,
ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,
N,N-dimethylamidocarbonyl, N-benzylamidocarbonyl,
N-(2-chlorobenzyl)amidocarbonyl, N-(3-fluorobenzyl)amidocarbonyl,
N-(2-trifluoromethylbenzyl)amidocarbonyl- ,
N-(1-phenylethyl)amidocarbonyl,
N-(1-methyl-1-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl,
N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl,
N-isopropylamidocarbonyl, N-propylamidocarbonyl,
N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,
N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl,
N-cyclohexylamidocarbonyl, fluoro, chloro, bromo, cyano,
cyclobutoxy, cyclohexoxy, cyclohexylmethoxy,
4-trifluoromethycyclohexylmethoxy, cyclopentoxy, benzyl, benzyloxy,
4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy,
4-bromobenzylamino, 5-bromopyrid-2-ylmethylamino,
4-butoxyphenamino, 3-chlorobenzyl, 4-chlorophenoxy,
4-chloro-3-ethylphenoxy, 4-chloro-3-ethylbenzylamino,
4-chloro-3-ethylphenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy,
4-chlorobenzylsulfonyl, 4-chlorophenylamino,
4-chlorophenylsulfonyl, 5-chloropyrid-3-yloxy,
2-cyanopyrid-3-yloxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy,
3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorophenoxy,
3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy,
2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy,
5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyloxy,
3,5-dimethylbenzyloxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy,
3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy,
4-fluorobenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy,
3-fluoro-5-trifluoromethylbenzyloxy,
4-fluoro-2-trifluoromethylbenzyloxy,
4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy,
4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy,
2-fluorobenzyloxy, 4-fluorophenylamino,
2-fluorotrifluoromethylphenoxy, 4-isopropylbenzyloxy,
3-isopropylphenoxy, 4-isopropylphenoxy,
4-isopropyl-3-methylphenoxy, 4-isopropylbenzyloxy,
3-isopropylphenoxy, 4-isopropylphenoxy,
4-isopropyl-3-methylphenoxy, phenylamino, 1-phenylethoxy,
2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino, phenylsulfonyl,
3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy,
3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy,
3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy,
2,4-bis-trifluoromethylbenzyloxy, 3-trifluoromethylbenzyl,
3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy,
3-trifluoromethylphenoxy, 3-trifluoromethylthiobenzyloxy,
4-trifluoromethylthiobenzyloxy, 2,3,4-trifluorophenoxy,
2,3,5-trifluorophenoxy, 3-pentafluoroethylphenoxy,
3-(1,1,2,2-tetrafluoroethoxy)phenoxy, and
3-trifluoromethylthiophenoxy;
[0566] Y.sup.0 is selected from the group of formulas consisting
of: 464748
[0567] Q.sup.s is selected from the group consisting of a bond,
CH.sub.2 and CH.sub.2CH.sub.2.
[0568] In a most preferred specific embodiment of Formula I,
compounds have the formula: 49
[0569] or a pharmaceutically acceptable salt thereof, wherein;
[0570] B is selected from the group consisting of phenyl,
2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,
2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl,
3-isoxazolyl, and 5-isoxazolyl, wherein a carbon adjacent to the
carbon at the point of attachment of said phenyl or heteroaryl ring
to A is optionally substituted by R.sup.32, the other carbon
adjacent to the carbon at the point of attachment is optionally
substituted by R.sup.36, a carbon adjacent to R.sup.32 and two
atoms from the carbon at the point of attachment is optionally
substituted by R.sup.33, a carbon adjacent to R.sup.36 and two
atoms from the carbon at the point of attachment is optionally
substituted by R.sup.35, and any carbon adjacent to both R.sup.33
and R.sup.35 is optionally substituted by R.sup.34;
[0571] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino,
N-methylamino, dimethylamino, methoxyamino, methylthio, ethylthio,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro,
chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl,
amidocarbonyl, carboxy, cyano, and Q.sup.b;
[0572] A is selected from the group consisting of a bond, NH,
N(CH.sub.3), CH.sub.2, CH.sub.3CH, and CH.sub.2CH.sub.2;
[0573] Q.sup.b is NR.sup.20R.sup.21 or
C(NR.sup.25)NR.sup.23R.sup.24;
[0574] R.sup.20, R.sup.21, R.sup.23, R.sup.24, and R.sup.25 are
independently selected from the group consisting of hydrido,
methyl, and ethyl.
[0575] In another most preferred specific embodiment of Formula I,
compounds have the formula: 50
[0576] or a pharmaceutically acceptable salt thereof, wherein;
[0577] B is selected from the group consisting of hydrido, ethyl,
2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl,
2-butynyl, sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl,
1-pentyl, 2-pentenyl, 3-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl,
3-pentyl, 2-methylbutyl, 2-methyl-2-butenyl, 3-methylbutyl,
3-methyl-2-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl,
2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl,
1-methyl-3-pentenyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl,
3-hexyl, 1-ethyl-2-butenyl, 1-heptyl, 2-heptenyl, 3-heptenyl,
4-heptenyl, 5-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl,
5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl,
1-methylhexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl,
1-methylhexynyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl,
1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 2,2,2-trifluoroethyl,
2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl,
4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and
3,3,3-trifluoropropyl, wherein each member of group B is optionally
substituted at any carbon up to and including 5 atoms from the
point of attachment of B to A with one or more of the group
consisting of R.sup.32 , R.sup.33 , R.sup.34, R.sup.35, and
R.sup.36;
[0578] R.sup.32, R.sup.33, R.sup.34, R.sup.35, and R.sup.36 are
independently selected from the group consisting of hydrido,
amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino,
N-methylamino, dimethylamino, methoxyamino, methylthio, ethylthio,
trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro,
chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl,
amidocarbonyl, carboxy, cyano, and Q.sup.b;
[0579] A is selected from the group consisting of a bond, NH,
N(CH.sub.3), CH.sub.2, CH.sub.3CH, and CH.sub.2CH.sub.2;
[0580] A is optionally selected from the group consisting of
CH.sub.2N(CH.sub.3), CH.sub.2N(CH.sub.2CH.sub.3),
CH.sub.2CH.sub.2N(CH.su- b.3), and
CH.sub.2CH.sub.2N(CH.sub.2CH.sub.3) with the proviso that B is
hydrido;
[0581] Q.sup.b is selected from the group consisting of
NR.sup.20R.sup.21, C(NR.sup.25)NR.sup.23R.sup.24, and
N(R.sup.26)C(NR.sup.25)N(R.sup.23)(R.s- up.24);
[0582] R.sup.20, R.sup.21, R.sup.23, R.sup.24, R.sup.25, and
R.sup.26 are independently selected from the group consisting of
hydrido, methyl, and ethyl.
[0583] In still another most preferred specific embodiment of
Formula I, compounds have the formula: 51
[0584] or a pharmaceutically acceptable salt thereof, wherein;
[0585] B is selected from the group consisting of cyclopropyl,
cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxalan-2-yl,
2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl, azetidin-1-yl,
azetidin-2-yl, azetidin-3-yl, bicyclo[3.1.0]hexan-6-yl,
2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl,
2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl,
4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl,
2-dioxanyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl,
2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl,
2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring
carbon is optionally substituted with R.sup.33, ring carbons and a
nitrogen adjacent to the carbon atom at the point of attachment are
optionally substituted with R.sup.9 or R.sup.13, a ring carbon or
nitrogen adjacent to the R.sup.9 position and two atoms from the
point of attachment are optionally substituted with R.sup.10, and a
ring carbon or nitrogen atom adjacent to the R.sup.13 position and
two atoms from the point of attachment is optionally substituted
with R.sup.12;
[0586] R.sup.33 is selected from the group consisting of hydrido,
amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy,
carboxy, amino, N-methylamino, dimethylamino, methoxyamino,
methylthio, ethylthio, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,
N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, cyano, and
Q.sup.b;
[0587] A is selected from the group consisting of a bond, NH,
N(CH.sub.3), CH.sub.2, CH.sub.3CH, CH.sub.2CH.sub.2, and
CH.sub.2CH.sub.2CH.sub.2;
[0588] Q.sup.b is NR.sup.20 R.sup.21 or
C(NR.sup.25)NR.sup.23R.sup.24;
[0589] R.sup.20, R.sup.21, R.sup.23, R.sup.24, and R.sup.25 are
independently selected from the group consisting of hydrido,
methyl, and ethyl.
[0590] The most preferred specific embodiment compounds of Formula
I said compounds having the formula: 52
[0591] or a pharmaceutically acceptable salt thereof, have common
structural units, wherein;
[0592] X.sup.O is selected from the group consisting of hydrido,
hydroxy, amino, amidino, aminomethyl, cyano, methyl,
trifluoromethyl, hydroxymethyl, chloro, and fluoro;
[0593] R.sup.2 is selected from the group consisting of phenyl,
2-thienyl, 2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl,
3-isoxazolyl, 2-pyridyl, and 3-pyridyl, wherein a carbon adjacent
to the carbon at the point of attachment of said phenyl or
heteroaryl ring to the 1,4-quinone ring is optionally substituted
by R.sup.9, the other carbon adjacent to the carbon at the point of
attachment is optionally substituted by R.sup.13, a carbon adjacent
to R.sup.9 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.10, a carbon adjacent to
R.sup.13 and two atoms from the carbon at the point of attachment
is optionally substituted by R.sup.12, and any carbon adjacent to
both R.sup.10 and R.sup.12 is optionally substituted by
R.sup.11;
[0594] R.sup.9, R.sup.11, and R.sup.13 are independently selected
from the group consisting of hydrido, methyl, ethyl, methoxy,
ethoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino,
methylthio, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,
N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,
1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy, and
cyano;
[0595] R.sup.10 and R.sup.12 are independently selected from the
group consisting of hydrido, amidino, amidocarbonyl,
N-methylamidocarbonyl, N-benzylamidocarbonyl,
N-(2-chlorobenzyl)amidocarbonyl, N-(3-fluorobenzyl)amidocarbonyl,
N-(2-trifluoromethylbenzyl)amidocarbonyl- ,
N-(1-phenylethyl)amidocarbonyl,
N-(1-methyl-1-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl,
N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl,
N-isopropylamidocarbonyl, N-propylamidocarbonyl,
N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,
N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl,
N-cyclohexylamidocarbonyl, guanidino, methyl, ethyl, methoxy,
ethoxy, hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
carboxy, carboxymethyl, amino, acetamido, trifluoromethyl,
pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido,
aminomethyl, N-methylamino, dimethylamino, methoxyamino,
amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,
methanesulfonamido, methoxycarbonyl, fluoro, chloro, bromo, and
cyano;
[0596] Y.sup.0 is selected from the group of formulas consisting
of: 5354
[0597] R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are independently
selected from the group consisting of hydrido, methyl, ethyl,
amidino, guanidino, methoxy, hydroxy, amino, aminomethyl,
1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,
methylthio, ethylthio, trifluoromethylthio, methylsulfinyl,
methylsulfonyl, trifluoromethyl, pentafluoroethyl,
2,2,2-trifluoroethyl, trifluoromethoxy, fluoro, chloro,
hydroxymethyl, carboxy, and cyano;
[0598] Q.sup.s is CH.sub.2.
[0599] The compounds of this invention can be used in anticoagulant
therapy for the treatment and prevention of a variety of thrombotic
conditions including coronary artery and cerebrovascular disease.
The compounds of this invention can be used to inhibit serine
protease associated with the coagulation cascade and factors II,
VII, VIII, IX, X, XI, or XII. The compounds of the invention can
inhibit the formation of blood platelet aggregates, inhibit the
formation of fibrin, inhibit thrombus formation, and inhibiting
embolus formation in a mammal, in blood, in blood products, and in
mammalian organs. The compounds also can be used for treating or
preventing unstable angina, refractory angina, myocardial
infarction, transient ischemic attacks, atrial fibrillation,
thrombotic stroke, embolic stroke, deep vein thrombosis,
disseminated intravascular coagulation, ocular build up of fibrin,
and reocclusion or restenosis of recanalized vessels in a mammal.
The compounds can also be used in prophylactic treatment of
subjects who are at risk of developing such disorders. The
compounds can be used to lower the risk of atherosclerosis. The
compounds of Formula (I) would also be useful in prevention of
cerebral vascular accident (CVA) or stroke.
[0600] Besides being useful for human treatment, these compounds
are also useful for veterinary treatment of companion animals,
exotic animals and farm animals, including mammals, rodents, and
the like. More preferred animals include horses, dogs, and
cats.
[0601] In yet another embodiment of the present invention, the
novel compounds are selected from the compounds set forth in Table
1.
[0602] The use of generic terms in the description of the compounds
are herein defined for clarity.
[0603] Standard single letter elemental symbols are used to
represent specific types of atoms unless otherwise defined. The
symbol "C" represents a carbon atom. The symbol "O" represents an
oxygen atom. The symbol "N" represents a nitrogen atom. The symbol
"P" represents a phosphorus atom. The symbol "S" represents a
sulfur atom. The symbol "H" represents a hydrogen atom. Double
letter elemental symbols are used as defined for the elements of
the periodical table (i.e., Cl represents chlorine, Se represents
selenium, etc.).
[0604] As utilized herein, the term "alkyl", either alone or within
other terms such as "haloalkyl" and "alkylthio", means an acyclic
alkyl radical containing from 1 to about 10, preferably from 3 to
about 8 carbon atoms and more preferably 3 to about 6 carbon atoms.
Said alkyl radicals may be optionally substituted with groups as
defined below. Examples of such radicals include methyl, ethyl,
chloroethyl, hydroxyethyl, n-propyl, oxopropyl, isopropyl, n-butyl,
cyanobutyl, isobutyl, sec-butyl, tert-butyl, pentyl, aminopentyl,
iso-amyl, hexyl, octyl and the like.
[0605] The term "alkenyl" refers to an unsaturated, acyclic
hydrocarbon radical in so much as it contains at least one double
bond. Such alkenyl radicals contain from about 2 to about 10 carbon
atoms, preferably from about 3 to about 8 carbon atoms and more
preferably 3 to about 6 carbon atoms. Said alkenyl radicals may be
optionally substituted with groups as defined below. Examples of
suitable alkenyl radicals include propenyl, 2-chloropropenyl,
buten-1-yl, isobutenyl, penten-1-yl, 2-2-methylbuten-1-yl,
3-methylbuten-1-yl, hexen-1-yl, 3-hydroxyhexen-1-yl,hepten-1-yl,
and octen-1-yl, and the like.
[0606] The term "alkynyl" refers to an unsaturated, acyclic
hydrocarbon radical in so much as it contains one or more triple
bonds, such radicals containing about 2 to about 10 carbon atoms,
preferably having from about 3 to about 8 carbon atoms and more
preferably having 3 to about 6 carbon atoms. Said alkynyl radicals
may be optionally substituted with groups as defined below.
Examples of suitable alkynyl radicals include ethynyl, propynyl,
hydroxypropynyl, butyn-1-yl, butyn-2-yl, pentyn-1-yl, pentyn-2-yl,
4-methoxypentyn-2-yl, 3-methylbutyn-1-yl, hexyn-1-yl, hexyn-2-yl,
hexyn-3-yl, 3,3-dimethylbutyn-1-yl radicals and the like.
[0607] The term "hydrido" denotes a single hydrogen atom (H). This
hydrido radical may be attached, for example, to an oxygen atom to
form a "hydroxyl" radical, one hydrido radical may be attached to a
carbon atom to form a "methine" radical --CH.dbd., or two hydrido
radicals may be attached to a carbon atom to form a "methylene"
(--CH.sub.2--) radical.
[0608] The term "carbon" radical denotes a carbon atom without any
covalent bonds and capable of forming four covalent bonds.
[0609] The term "cyano" radical denotes a carbon radical having
three of four covalent bonds shared by a nitrogen atom.
[0610] The term "hydroxyalkyl" embraces radicals wherein any one or
more of the alkyl carbon atoms is substituted with a hydroxyl as
defined above. Specifically embraced are monohydroxyalkyl,
dihydroxyalkyl and polyhydroxyalkyl radicals.
[0611] The term "alkanoyl" embraces radicals wherein one or more of
the terminal alkyl carbon atoms are substituted with one or more
carbonyl radicals as defined below. Specifically embraced are
monocarbonylalkyl and dicarbonylalkyl radicals. Examples of
monocarbonylalkyl radicals include formyl, acetyl, and pentanoyl.
Examples of dicarbonylalkyl radicals include oxalyl, malonyl, and
succinyl.
[0612] The term "alkylene" radical denotes linear or branched
radicals having from 1 to about 10 carbon atoms and having
attachment points for two or more covalent bonds. Examples of such
radicals are methylene, ethylene, methylethylene, and
isopropylidene.
[0613] The term "alkenylene" radical denotes linear or branched
radicals having from 2 to about 10 carbon-atoms, at least one
double bond, and having attachment points for two or more covalent
bonds. Examples of such radicals are 1,1-vinylidene
(CH.sub.2.dbd.C), 1,2-vinylidene (--CH.dbd.CH--), and
1,4-butadienyl (--CH.dbd.CH--CH.dbd.CH--).
[0614] The term "halo" means halogens such as fluorine, chlorine,
bromine or iodine atoms.
[0615] The term "haloalkyl" embraces radicals wherein any one or
more of the alkyl carbon atoms is substituted with halo as defined
above. Specifically embraced are monohaloalkyl, dihaloalkyl and
polyhaloalkyl radicals. A monohaloalkyl radical, for one example,
may have either a bromo, chloro or a fluoro atom within the
radical. Dihalo radicals may have two or more of the same halo
atoms or a combination of different halo radicals and polyhaloalkyl
radicals may have more than two of the same halo atoms or a
combination of different halo radicals. More preferred haloalkyl
radicals are "haloalkyl" radicals having one to about six carbon
atoms. Examples of such haloalkyl radicals include fluoromethyl,
difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl,
trichloromethyl, trifluoroethyl, pentafluoroethyl,
heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl,
difluoroethyl, difluoropropyl, dichloroethyl and
dichloropropyl.
[0616] The term "hydroxyhaloalkyl" embraces radicals wherein any
one or more of the haloalkyl carbon atoms is substituted with
hydroxy as defined above. Examples of "hydroxyhaloalkyl" radicals
include hexafluorohydroxypropyl.
[0617] The term "haloalkylene radical" denotes alkylene radicals
wherein any one or more of the alkylene carbon atoms is substituted
with halo as defined above. Dihalo alkylene radicals may have two
or more of the same halo atoms or a combination of different halo
radicals and polyhaloalkylene radicals may have more than two of
the same halo atoms or a combination of different halo radicals.
More preferred haloalkylene radicals are "haloalkylene" radicals
having one to about six carbon atoms. Examples of "haloalkylene"
radicals include difluoromethylene, tetrafluoroethylene,
tetrachloroethylene, alkyl substituted monofluoromethylene, and
aryl substituted trifluoromethylene.
[0618] The term "haloalkenyl" denotes linear or branched radicals
having from 1 to about 10 carbon atoms and having one or more
double bonds wherein any one or more of the alkenyl carbon atoms is
substituted with halo as defined above. Dihaloalkenyl radicals may
have two or more of the same halo atoms or a combination of
different halo radicals and polyhaloalkenyl radicals may have more
than two of the same halo atoms or a combination of different halo
radicals.
[0619] The terms "alkoxy" and "alkoxyalkyl" embrace linear or
branched oxy-containing radicals each having alkyl portions of one
to about ten carbon atoms, such as methoxy radical. The term
"alkoxyalkyl" also embraces alkyl radicals having one or more
alkoxy radicals attached to the alkyl radical, that is, to form
monoalkoxyalkyl and dialkoxyalkyl radicals. More preferred alkoxy
radicals are "alkoxy" radicals having one to six carbon atoms.
Examples of such radicals include methoxy, ethoxy, propoxy, butoxy,
isopropoxy and tert-butoxy alkyls. The "alkoxy" radicals may be
further substituted with one or more halo atoms, such as fluoro,
chloro or bromo, to provide "haloalkoxy" and "haloalkoxyalkyl"
radicals. Examples of such haloalkoxy radicals include
fluoromethoxy, chloromethoxy, trifluoromethoxy, difluoromethoxy,
trifluoroethoxy, fluoroethoxy, tetrafluoroethoxy,
pentafluoroethoxy, and fluoropropoxy. Examples of such
haloalkoxyalkyl radicals include fluoromethoxymethyl,
chloromethoxyethyl, trifluoromethoxymethyl, difluoromethoxyethyl,
and trifluoroethoxymethyl.
[0620] The terms "alkenyloxy" and "alkenyloxyalkyl" embrace linear
or branched oxy-containing radicals each having alkenyl portions of
two to about ten carbon atoms, such as ethenyloxy or propenyloxy
radical. The term "alkenyloxyalkyl" also embraces alkenyl radicals
having one or more alkenyloxy radicals attached to the alkyl
radical, that is, to form monoalkenyloxyalkyl and dialkenyloxyalkyl
radicals. More preferred alkenyloxy radicals are "alkenyloxy"
radicals having two to six carbon atoms. Examples of such radicals
include ethenyloxy, propenyloxy, butenyloxy, and isopropenyloxy
alkyls. The "alkenyloxy" radicals may be further substituted with
one or more halo atoms, such as fluoro, chloro or bromo, to provide
"haloalkenyloxy" radicals. Examples of such radicals include
trifluoroethenyloxy, fluoroethenyloxy, difluoroethenyhloxy, and
fluoropropenyloxy.
[0621] The term "haloalkoxyalkyl" also embraces alkyl radicals
having one or more haloalkoxy radicals attached to the alkyl
radical, that is, to form monohaloalkoxyalkyl and dihaloalkoxyalkyl
radicals. The term "haloalkenyloxy" also embraces oxygen radicals
having one or more haloalkenyloxy radicals attached to the oxygen
radical, that is, to form monohaloalkenyloxy and dihaloalkenyloxy
radicals. The term "haloalkenyloxyalkyl" also embraces alkyl
radicals having one or more haloalkenyloxy radicals attached to the
alkyl radical, that is, to form monohaloalkenyloxyalkyl and
dihaloalkenyloxyalkyl radicals.
[0622] The term "alkylenedioxy" radicals denotes alkylene radicals
having at least two oxygens bonded to a single alkylene group.
Examples of "alkylenedioxy" radicals include methylenedioxy,
ethylenedioxy, alkylsubstituted methylenedioxy, and arylsubstituted
methylenedioxy. The term "haloalkylenedioxy" radicals denotes
haloalkylene radicals having at least two oxy groups bonded to a
single haloalkyl group. Examples of "haloalkylenedioxy" radicals
include difluoromethylenedioxy, tetrafluoroethylenedioxy,
tetrachloroethylenedioxy, alkylsubstituted
monofluoromethylenedioxy, and arylsubstituted
monofluoromethylenedioxy.
[0623] The term "aryl", alone or in combination, means a
carbocyclic aromatic system containing one, two or three rings
wherein such rings may be attached together in a pendant manner or
may be fused. The term "fused" means that a second ring is present
(ie, attached or formed) by having two adjacent atoms in common
(ie, shared) with the first ring. The term "fused" is equivalent to
the term "condensed". The term "aryl" embraces aromatic radicals
such as phenyl, naphthyl, tetrahydronaphthyl, indane and
biphenyl.
[0624] The term "perhaloaryl" embraces aromatic radicals such as
phenyl, naphthyl, tetrahydronaphthyl, indane and biphenyl wherein
the aryl radical is substituted with 3 or more halo radicals as
defined below.
[0625] The term "heterocyclyl" embraces saturated and partially
saturated heteroatom-containing ring-shaped radicals having from 4
through 15 ring members, herein referred to as "C4-C15
heterocyclyl", selected from carbon, nitrogen, sulfur and oxygen,
wherein at least one ring atom is a heteroatom. Heterocyclyl
radicals may contain one, two or three rings wherein,such rings may
be attached in a pendant manner or may be fused. Examples of
saturated heterocyclic radicals include saturated 3 to 6-membered
heteromonocylic group containing 1 to 4 nitrogen atoms[e.g.
pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl, etc.];
saturated 3 to 6-membered heteromonocyclic group containing 1 to 2
oxygen atoms and 1 to 3 nitrogen atoms [e.g. morpholinyl, etc.];
saturated 3 to 6-membered heteromonocyclic group containing 1 to 2
sulfur atoms and 1 to 3 nitrogen atoms [e.g., thiazolidinyl, etc.].
Examples of partially saturated heterocyclyl radicals include
dihydrothiophene, dihydropyran, dihydrofuran and dihydrothiazole.
Non-limiting examples of heterocyclic radicals include
2-pyrrolinyl, 3-pyrrolinyl, pyrrolindinyl, 1,3-dioxolanyl,
2H-pyranyl, 4H-pyranyl, piperidinyl, 1,4-dioxanyl, morpholinyl,
1,4-dithianyl, thiomorpholinyl, and the like. Said "heterocyclyl"
group may be substituted as defined herein. Preferred heterocyclic
radicals include five to twelve membered fused or unfused
radicals.
[0626] The term "heteroaryl" embraces fully unsaturated
heteroatom-containing ring-shaped aromatic radicals having from 4
through 15 ring members selected from carbon, nitrogen, sulfur and
oxygen, wherein at least one ring atom is a heteroatom. Heteroaryl
radicals may contain one, two or three rings wherein such rings may
be attached in a pendant manner or may be fused. Examples of
"heteroaryl" radicals, include the unsaturated heteromonocyclyl
group of 5 to 6 contiguous members containing 1 to 4 nitrogen
atoms, for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl,
2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidyl, pyrazinyl, pyridazinyl,
triazolyl [e.g., 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl,
2H-1,2,3-triazolyl, etc.] tetrazolyl [e.g. 1H-tetrazolyl,
2H-tetrazolyl, etc.], etc.; unsaturated condensed heterocyclic
group containing 1 to 5 nitrogen atoms, for example, indolyl,
isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl,
indazolyl, benzotriazolyl, tetrazolopyridazinyl [e.g., tetrazolo
[1,5b]pyridazinyl, etc.], etc.; unsaturated 3 to 6-membered
heteromonocyclic group containing an oxygen atom, for example,
pyranyl, 2-furyl, 3-furyl, etc.; unsaturated 5 to 6-membered
heteromonocyclic group containing a sulfur atom, for example,
2-thienyl, 3-thienyl, etc.; unsaturated 5- to 6-membered
heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3
nitrogen atoms, for example, oxazolyl, isoxazolyl, oxadiazolyl
[e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl,
etc.] etc.; unsaturated condensed heterocyclic group containing 1
to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g. benzoxazolyl,
benzoxadiazolyl, etc.]; unsaturated 5 to 6-membered
heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3
nitrogen atoms, for example, thiazolyl, thiadiazolyl [e.g.,
1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc.]
etc.; unsaturated condensed heterocyclic group containing 1 to 2
sulfur atoms and 1 to 3 nitrogen atoms [e.g., benzothiazolyl,
benzothiadiazolyl, etc.] and the like. The term also embraces
radicals where heterocyclic radicals are fused with aryl radicals.
Examples of such fused bicyclic radicals include benzofuran,
benzothiophene, and the like. Said "heteroaryl" group may be
substituted as defined herein. Preferred heteroaryl radicals
include five and six membered unfused radicals. Non-limiting
examples of heteroaryl radicals include 2-thienyl, 3-thienyl,
2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,
4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 1,2,4-triazol-3-yl,
1,2,4-triazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl,
1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl, 3-isothiazolyl,
5-isothiazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl,
5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl,
2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,
4-pyridazinyl, 1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl,
1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl, 1,2,3-triazin-4-yl, and
1,2,3-triazin-5-yl, and the like.
[0627] The term "sulfonyl", whether used alone or linked to other
terms such as alkylsulfonyl, denotes respectively divalent radicals
--SO.sub.2--. "Alkylsulfonyl", embraces alkyl radicals attached to
a sulfonyl radical, where alkyl is defined as above.
"Alkylsulfonylalkyl", embraces alkylsulfonyl radicals attached to
an alkyl radical, where alkyl is defined as above.
"Haloalkylsulfonyl", embraces haloalkyl radicals attached to a
sulfonyl radical, where haloalkyl is defined as above.
"Haloalkylsulfonylalkyl", embraces haloalkylsulfonyl radicals
attached to an alkyl radical, where alkyl is defined as above.
[0628] The term "amidosulfonyl" embraces amino, monoalkylamino,
dialkylamino, monocycloalkylamino, alkyl cycloalkylamino,
dicycloalkylamino, N-alkyl-N-arylamino, arylamino, aralkylamino,
nitrogen containing heterocyclyl, heterocyclylamino,
N-alkyl-N-heterocyclylamino, heteroarylamino, and
heteroaralkylamino radicals, attached to one of two unshared bonds
in a sulfonyl radical.
[0629] The term "sulfinyl", whether used alone or linked to other
terms such as alkylsulfinyl, denotes respectively divalent radicals
--S(O)--. "Alkylsulfinyl", embraces alkyl radicals attached to a
sulfinyl radical, where alkyl is defined as above.
"Alkylsulfinylalkyl", embraces alkylsulfinyl radicals attached to
an alkyl radical, where alkyl is -defined as above.
"Haloalkylsulfinyl", embraces haloalkyl radicals attached to a
sulfinyl radical, where haloalkyl is defined as above.
"Haloalkylsulfinylalkyl", embraces haloalkylsulfinyl radicals
attached to an alkyl radical, where alkyl is defined as above.
[0630] The term "aralkyl" embraces aryl-substituted alkyl radicals.
Preferable aralkyl radicals are "aralkyl" radicals having aryl
radicals attached to alkyl radicals having one to six carbon atoms.
Examples of such radicals include benzyl, diphenylmethyl,
triphenylmethyl, phenylethyl and diphenylethyl. The terms benzyl
and phenylmethyl are interchangeable.
[0631] The term "heteroaralkyl" embraces heteroaryl-substituted
alkyl radicals wherein the heteroaralkyl radical may be
additionally substituted with three or more substituents as defined
above for aralkyl radicals. The term "perhaloaralkyl" embraces
aryl-substituted alkyl radicals wherein the aralkyl radical is
substituted with three or more halo radicals as defined above.
[0632] The term "aralkylsulfinyl", embraces aralkyl radicals
attached to a sulfinyl radical, where aralkyl is defined as above.
"Aralkylsulfinylalkyl", embraces aralkylsulfinyl radicals attached
to an alkyl radical, where alkyl is defined as above.
[0633] The term "aralkylsulfonyl", embraces aralkyl radicals
attached to a sulfonyl radical, where aralkyl is defined as above.
"Aralkylsulfonylalkyl", embraces aralkylsulfonyl radicals attached
to an alkyl radical, where alkyl is defined as above.
[0634] The term "cycloalkyl" embraces radicals having three to 15
carbon atoms. More preferred cycloalkyl radicals are "cycloalkyl"
radicals having three to seven carbon atoms. Examples include
radicals such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl
and cycloheptyl. The term cycloalkyl embraces radicals having seven
to 15 carbon atoms and having two to four rings. Exmaples incude
radicals such as norbornyl (i.e., bicyclo[2.2.1]heptyl) and
adamantyl. The term "cycloalkylalkyl" embraces
cycloalkyl-substituted alkyl radicals. Preferable cycloalkylalkyl
radicals are "cycloalkylalkyl" radicals having cycloalkyl radicals
attached to alkyl radicals having one to six carbon atoms. Examples
of such radicals include cyclohexylhexyl. The term "cycloalkenyl"
embraces radicals having three to ten carbon atoms and one or more
carbon-carbon double bonds. Preferred cycloalkenyl radicals are
"cycloalkenyl" radicals having three to seven carbon atoms.
Examples include radicals such as cyclobutenyl, cyclopentenyl,
cyclohexenyl and cycloheptenyl. The term "halocycloalkyl" embraces
radicals wherein any one or more of the cycloalkyl carbon atoms is
substituted with halo as defined above. Specifically embraced are
monohalocycloalkyl, dihalocycloalkyl and polyhalocycloalkyl
radicals. A monohalocycloalkyl radical, for one example, may have
either a bromo, chloro or a fluoro atom within the radical. Dihalo
radicals may have two or more of the same halo atoms or a
combination of different halo radicals and polyhalocycloalkyl
radicals may have more than two of the same halo atoms or a
combination of different halo radicals. More preferred
halocycloalkyl radicals are "halocycloalkyl" radicals having three
to about eight carbon atoms. Examples of such halocycloalkyl
radicals include fluorocyclopropyl, difluorocyclobutyl,
trifluorocyclopentyl, tetrafluorocyclohexyl, and
dichlorocyclopropyl. The term "halocycloalkenyl" embraces radicals
wherein any one or more of the cycloalkenyl carbon atoms is
substituted with halo as defined above. Specifically embraced are
monohalocycloalkenyl, dihalocycloalkenyl and polyhalocycloalkenyl
radicals.
[0635] The term "cycloalkoxy" embraces cycloalkyl radicals attached
to an oxy radical. Examples of such radicals includes cyclohexoxy
and cyclopentoxy. The term "cycloalkoxyalkyl" also embraces alkyl
radicals having one or more cycloalkoxy radicals attached to the
alkyl radical, that is, to form monocycloalkoxyalkyl and
dicycloalkoxyalkyl radicals. Examples of such radicals include
cyclohexoxyethyl. The "cycloalkoxy" radicals may be further
substituted with one or more halo atoms, such as fluoro, chloro or
bromo, to provide "halocycloalkoxy" and "halocycloalkoxyalkyl"
radicals.
[0636] The term "cycloalkylalkoxy" embraces cycloalkyl radicals
attached to an alkoxy radical. Examples of such radicals includes
cyclohexylmethoxy and cyclopentylmethoxy.
[0637] The term "cycloalkenyloxy" embraces cycloalkenyl radicals
attached to an oxy radical. Examples of such radicals includes
cyclohexenyloxy and cyclopentenyloxy. The term
"cycloalkenyloxyalkyl" also embraces alkyl radicals having one or
more cycloalkenyloxy radicals attached to the alkyl radical, that
is, to form monocycloalkenyloxyalkyl and dicycloalkenyloxyalkyl
radicals. Examples of such radicals include cyclohexenyloxyethyl.
The "cycloalkenyloxy" radicals may be further substituted with one
or more halo atoms, such as fluoro, chloro or bromo, to provide
"halocycloalkenyloxy" and "halocycloalkenyloxyalkyl" radicals.
[0638] The term "cycloalkylenedioxy" radicals denotes cycloalkylene
radicals having at least two oxygens bonded to a single
cycloalkylene group. Examples of "alkylenedioxy" radicals include
1,2-dioxycyclohexylene.
[0639] The term "cycloalkylsulfinyl", embraces cycloalkyl radicals
attached to a sulfinyl radical, where cycloalkyl is defined as
above. "Cycloalkylsulfinylalkyl", embraces cycloalkylsulfinyl
radicals attached to an alkyl radical, where alkyl is defined as
above. The term "Cycloalkylsulfonyl", embraces cycloalkyl radicals
attached to a sulfonyl radical, where cycloalkyl is defined as
above. "Cycloalkylsulfonylalkyl", embraces cycloalkylsulfonyl
radicals attached to an alkyl radical, where alkyl is defined as
above.
[0640] The term "cycloalkylalkanoyl" embraces radicals wherein one
or more of the cycloalkyl carbon atoms are substituted with one or
more carbonyl radicals as defined below. Specifically embraced are
monocarbonylcycloalkyl and dicarbonylcycloalkyl radicals. Examples
of monocarbonylcycloalkyl radicals include cyclohexylcarbonyl,
cyclohexylacetyl, and cyclopentylcarbonyl. Examples of
dicarbonylcycloalkyl radicals include
1,2-dicarbonylcyclohexane.
[0641] The term "alkylthio" embraces radicals containing a linear
or branched alkyl radical, of one to ten carbon atoms, attached to
a divalent sulfur atom. More preferred alkylthio radicals are
"alkylthio" radicals having one to six carbon atoms. An example of
"alkylthio" is methylthio (CH.sub.3--S--). The "alkylthio" radicals
may be further substituted with one or more halo atoms, such as
fluoro, chloro or bromo, to provide "haloalkylthio" radicals.
Examples of such radicals include fluoromethylthio,
chloromethylthio, trifluoromethylthio, difluoromethylthio,
trifluoroethylthio, fluoroethylthio, tetrafluoroethylthio,
pentafluoroethylthio, and fluoropropylthio.
[0642] The term "alkyl aryl amino" embraces radicals containing a
linear or branched alkyl radical, of one to ten carbon atoms, and
one aryl radical both attached to an amino radical. Examples
include N-methyl-4-methoxyaniline, N-ethyl-4-methoxyaniline, and
N-methyl-4-trifluoromethoxyaniline.
[0643] The term alkylamino denotes "monoalkylamino" and
"dialkylamino" containing one or two alkyl radicals, respectively,
attached to an amino radical. One or two alkyl radicals of the
alkylamino may be optionally substituted with hydrogen bonding
substitutents selected from the group consisting of hydroxy, amino,
monoalkylamino, dialkylamino, amidino, guanidino, thiol, and alkoxy
provided the alkyl radicals comprises two or more carbons.
[0644] The terms arylamino denotes "monoarylamino" and
"diarylamino" containing one or two aryl radicals, respectively,
attached to an amino radical. Examples of such radicals include
N-phenylamino and N-naphthylamino.
[0645] The term "aralkylamino", embraces aralkyl radicals attached
to an amino radical, where aralkyl is defined as above. The term
aralkylamino denotes "monoaralkylamino" and "diaralkylamino"
containing one or two aralkyl radicals, respectively, attached to
an amino radical. The term aralkylamino further denotes
"monoaralkyl monoalkylamino" containing one aralkyl radical and one
alkyl radical attached to an amino radical.
[0646] The term "arylsulfinyl" embraces radicals-containing an aryl
radical, as defined above, attached to a divalent S(O) atom. The
term "arylsulfinylalkyl" denotes arylsulfinyl radicals attached to
a linear or branched alkyl radical, of one to ten carbon atoms.
[0647] The term "arylsulfonyl", embraces aryl radicals attached to
a sulfonyl radical, where aryl is defined as above.
"arylsulfonylalkyl", embraces arylsulfonyl radicals attached to an
alkyl radical, where alkyl is defined as above. The term
"heteroarylsulfinyl" embraces radicals containing an heteroaryl
radical, as defined above, attached to a divalent S(O) atom. The
term "heteroarylsulfinylalkyl" denotes heteroarylsulfinyl radicals
attached to a linear or branched alkyl radical, of one to ten
carbon atoms. The term "Heteroarylsulfonyl", embraces heteroaryl
radicals attached to a sulfonyl radical, where heteroaryl is
defined as above. "Heteroarylsulfonylalkyl", embraces
heteroarylsulfonyl radicals attached to an alkyl radical, where
alkyl is defined as above.
[0648] The term "aryloxy" embraces aryl radicals, as defined above,
attached to an oxygen atom. Examples of such radicals include
phenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-methylphenoxy,
3-chloro-4-ethylphenoxy, 3,4-dichlorophenoxy, 4-methylphenoxy,
3-trifluoromethoxyphenoxy, 3-trifluoromethylphenoxy,
4-fluorophenoxy, 3,4-dimethylphenoxy, 5-bromo-2-fluorophenoxy,
4-bromo-3-fluorophenoxy, 4-fluoro-3-methylphenoxy,
5,6,7,8-tetrahydronaphthyloxy, 3-isopropylphenoxy,
3-cyclopropylphenoxy, 3-ethylphenoxy, 3-pentafluoroethylphenoxy,
3-(1,1,2,2-tetrafluoroethoxy)-phenoxy, and 4-tert-butylphenoxy.
[0649] The term "aroyl" embraces aryl radicals, as defined above,
attached to an carbonyl radical as defined above. Examples of such
radicals include benzoyl and toluoyl.
[0650] The term "aralkanoyl" embraces aralkyl radicals, as defined
herein, attached to an carbonyl radical as defined above. Examples
of such radicals include, for example, phenylacetyl.
[0651] The term "aralkoxy" embraces oxy-containing aralkyl radicals
attached through an oxygen atom to other radicals. More preferred
aralkoxy radicals are "aralkoxy" radicals having phenyl radicals
attached to alkoxy radical as described above. Examples of such
radicals include benzyloxy, 1-phenylethoxy,
3-trifluoromethoxybenzyloxy, 3-trifluoromethylbenzyloxy,
3,5-difluorobenyloxy, 3-bromobenzyloxy, 4-propylbenzyloxy,
2-fluoro-3-trifluoromethylbenzyloxy, and 2-phenylethoxy.
[0652] The term "aryloxyalkyl" embraces aryloxy radicals, as
defined above, attached to an alkyl group. Examples of such
radicals include phenoxymethyl.
[0653] The term "haloaryloxyalkyl" embraces aryloxyalkyl radicals,
as defined above, wherein one to five halo radicals are attached to
an aryloxy group.
[0654] The term "heteroaroyl" embraces heteroaryl radicals, as
defined above, attached to an carbonyl radical as defined above.
Examples of such radicals include furoyl and nicotinyl.
[0655] The term "heteroaralkanoyl" embraces heteroaralkyl radicals,
as defined herein, attached to an carbonyl radical as defined
above. Examples of such radicals include, for example,
pyridylacetyl and furylbutyryl.
[0656] The term "heteroaralkoxy" embraces oxy-containing
heteroaralkyl radicals attached through an oxygen atom to other
radicals. More preferred heteroaralkoxy radicals are
"heteroaralkoxy" radicals having heteroaryl radicals attached to
alkoxy radical as described above. The term "heterocyclylalkoxy"
embraces oxy-containing heterocyclylalkyl radicals attached through
an oxygen atom to other radicals.
[0657] The term "haloheteroaryloxyalkyl" embraces
heteroaryloxyalkyl radicals, as defined above, wherein one to four
halo radicals are attached to an heteroaryloxy group.
[0658] The term "heteroarylamino" embraces heteroaryl radicals, as
defined above, attached to an amino group. Examples of such
radicals include pyridylamino. The term "heterocyclylamino"
embraces heterocyclyl radicals, as defined above, attached to an
amino group.
[0659] The term "heteroaralkylamino" embraces heteroaralkyl
radicals, as defined above, attached to an amino group. Examples of
such radicals include pyridylmethylamino. The term
"heterocyclylalkylamino" embraces heterocyclylalkyl radicals, as
defined above, attached to an amino group.
[0660] The term "heteroaryloxy" embraces heteroaryl radicals, as
defined above, attached to an oxy group. Examples of such radicals
include 2-thiophenyloxy, 2-pyrimidyloxy, 2-pyridyloxy,
3-pyridyloxy, and 4-pyridyloxy. The term "heterocyclyloxy" embraces
heterocyclyl radicals, as defined above, attached to an oxy
group.
[0661] The term "heteroaryloxyalkyl" embraces heteroaryloxy
radicals, as defined above, attached to an alkyl group. Examples of
such radicals include 2-pyridyloxymethyl, 3-pyridyloxyethyl, and
4-pyridyloxymethyl. The term "heterocyclyloxyalkyl" embraces
heterocyclyloxy radicals, as defined above, attached to an alkyl
group.
[0662] The term "arylthio" embraces aryl radicals, as defined
above, attached to an sulfur atom. Examples of such radicals
include phenylthio.
[0663] The term "arylthioalkyl" embraces arylthio radicals, as
defined above, attached to an alkyl group. Examples of such
radicals include phenylthiomethyl.
[0664] The term "alkylthioalkyl" embraces alkylthio radicals, as
defined above, attached to an alkyl group. Examples of such
radicals include methylthiomethyl. The term "alkoxyalkyl" embraces
alkoxy radicals, as defined above, attached to an alkyl group.
Examples of such radicals include methoxymethyl.
[0665] The term "carbonyl" denotes a carbon radical having two of
the four covalent bonds shared with an oxygen atom. The term
"carboxy" embraces a hydroxyl radical, as defined above, attached
to one of two unshared bonds in a carbonyl group. The term
"carboxamido" embraces amino, monoalkylamino, dialkylamino,
monocycloalkylamino, alkylcycloalkylamino, dicycloalkylamino,
N-alkyl-N-arylamino, arylamino, aralkylamino, nitrogen containing
heterocyclyl, heterocyclylamino, N-alkyl-N-heterocyclylamino,
heteroarylamino, and heteroaralkylamino radicals, attached to one
of two unshared bonds in a carbonyl group. The term
"carboxamidoalkyl" embraces carboxamido radicals, as defined above,
attached to an alkyl group. The term "carboxyalkyl" embraces a
carboxy radical, as defined above, attached to an alkyl group. The
term "carboalkoxy" embraces alkoxy radicals, as defined above,
attached to one of two unshared bonds in a carbonyl group. The term
"carboaralkoxy" embraces aralkoxy radicals, as defined above,
attached to one of two unshared bonds in a carbonyl group. The term
"monocarboalkoxyalkyl" embraces one carboalkoxy radical, as defined
above, attached to an alkyl group. The term "dicarboalkoxyalkyl"
embraces two carboalkoxy radicals, as defined above, attached to an
alkylene group. The term "monocyanoalkyl" embraces one cyano
radical, as defined above, attached to an alkyl group. The term
"dicyanoalkylene" embraces two cyano radicals, as defined above,
attached to an alkyl group. The term "carboalkoxycyanoalkyl"
embraces one cyano radical, as defined above, attached to an
carboalkoxyalkyl group.
[0666] The term "acyl", alone or in combination, means a carbonyl
or thionocarbonyl group bonded to a radical selected from, for
example, hydrido, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy,
alkoxyalkyl; haloalkoxy, aryl,-heterocyclyl, heteroaryl,
alkylsulfinylalkyl, alkylsulfonylalkyl, aralkyl, cycloalkyl,
cycloalkylalkyl, cycloalkenyl, alkylthio, arylthio, amino,
alkylamino, dialkylamino, aralkoxy, arylthio, and alkylthioalkyl.
Examples of "acyl" are formyl, acetyl, benzoyl, trifluoroacetyl,
phthaloyl, malonyl, nicotinyl, and the like. The term
"haloalkanoyl" embraces one or more halo radicals, as defined
herein, attached to an alkanoyl radical as defined above. Examples
of such radicals include, for example, chloroacetyl,
trifluoroacetyl, bromopropanoyl, and heptafluorobutanoyl.
[0667] The term "phosphono" embraces a pentavalent phosphorus
attached with two covalent bonds to an oxygen radical. The term
"dialkoxyphosphono" denotes two alkoxy radicals, as defined above,
attached to a phosphono radical with two covalent bonds. The term
"diaralkoxyphosphono" denotes two aralkoxy radicals, as defined
above, attached to a phosphono radical with two covalent bonds. The
term "dialkoxyphosphonoalkyl" denotes dialkoxyphosphono radicals,
as defined above, attached to an alkyl radical. The term
"diaralkoxyphosphonoalkyl" denotes diaralkoxyphosphono radicals, as
defined above, attached to an alkyl radical.
[0668] The term "amino" denotes a nitrogen atom containing two
substituents such as hydrido, hydroxy or alkyl and having one
covalent bond available for bonding to a single atom such as
carbon. Examples of such amino radicals include, for example,
--NH.sub.2, --NHCH.sub.3, --NHOH, and --NHOCH.sub.3. The term
"imino" denotes a nitrogen atom containing one substituent such as
hydrido, hydroxy or alkyl and having two covalent bonds available
for bonding to a single atom such as carbon. Examples of such imino
radicals include, for example, .dbd.NH, .dbd.NCH.sub.3, .dbd.NOH,
and .dbd.NOCH.sub.3. The term "imino carbonyl" denotes a carbon
radical having two of the four covalent bond sites shared with an
imino group. Examples of such imino carbonyl radicals include, for
example, C.dbd.NH, C.dbd.NCH.sub.3, C.dbd.NOH, and
C.dbd.NOCH.sub.3. The term "amidino" embraces a substituted or
unsubstituted amino group bonded to one of two available bonds of
an iminocarbonyl radical. Examples of such amidino radicals
include, for example, NH.sub.2--C.dbd.NH,
NH.sub.2--C.dbd.NCH.sub.3, NH.sub.2--C.dbd.NOCH.sub.3 and
CH.sub.3NH--C.dbd.NOH. The term "guanidino" denotes an amidino
group bonded to an amino group as defined above where said amino
group can be bonded to a third group. Examples of such guanidino
radicals include, for example, NH.sub.2--C(NH)--NH--,
NH.sub.2--C(NCH.sub.3)--NH--, NH.sub.2--C(NOCH.sub.3)--NH--, and
CH.sub.3NH--C(NOH)--NH--.
[0669] The term "sulfonium" denotes a positively charged trivalent
sulfur atom where said sulfur is substituted with three carbon
based groups such as alkyl, alkenyl, aralkyl, or aryl. The term
"dialkyl sulfonium" denotes a sulfonium group where said sulfur is
substituted with two alkyl groups. Examples of such
dialkylsulfonium radicals include, for example,
(CH.sub.3).sub.2S.sup.+--. The term "dialkyl sulfonium alkyl"
denotes a dialkyl sulfonium group where said group is bonded to one
bond of an alkylene group as defined above. Examples of such
dialkylsulfoniumalkyl radicals include (CH.sub.3
).sub.2S.sup.+--CH.sub.2CH.sub.2--.
[0670] The term "phosphonium" denotes a positively charged
tetravalent phosphorus atom where said phosphorus is substituted
with four carbon based groups such as alkyl, alkenyl, aralkyl, or
aryl. The term "trialkyl phosphonium" denotes a phosphonium group
where said phosphorus is substituted with three alkyl groups.
Examples of such trialkylphosphonium radicals include, for example,
(CH.sub.3).sub.3P.sup.+--.
[0671] Said "alkyl", "alkenyl", "alkynyl", "alkanoyl", "alkylene",
"alkenylene", "hydroxyalkyl", "haloalkyl", "haloalkylene",
"haloalkenyl", "alkoxy", "alkenyloxy", "alkenyloxyalkyl",
"alkoxyalkyl", "aryl", "perhaloaryl", "haloalkoxy",
"haloalkoxyalkyl", "haloalkenyloxy", "haloalkenyloxyalkyl",
"alkylenedioxy", "haloalkylenedioxy", "heterocyclyl", "heteroaryl",
"hydroxyhaloalkyl", "alkylsulfonyl", "haloalkylsulfonyl",
"alkylsulfonylalkyl", "haloalkylsulfonylalkyl", "alkylsulfinyl",
"alkylsulfinylalkyl", "haloalkylsulfinylalkyl", "aralkyl",
"heteroaralkyl", "perhaloaralkyl", "aralkylsulfonyl",
"aralkylsulfonylalkyl", "aralkylsulfinyl", "aralkylsulfinylalkyl",
"cycloalkyl", "cycloalkylalkanoyl", "cycloalkylalkyl",
"cycloalkenyl", "halocycloalkyl ", "halocycloalkenyl",
"cycloalkylsulfinyl", "cycloalkylsulfinylalkyl",
"cycloalkylsulfonyl", "cycloalkylsulfonylalkyl- ", "cycloalkoxy",
"cycloalkoxyalkyl", "cycloalkylalkoxy", "cycloalkenyloxy",
"cycloalkenyloxyalkyl ", "cycloalkylenedioxy", "halocycloalkoxy",
"halocycloalkoxyalkyl", "halocycloalkenyloxy",
"halocycloalkenyloxyalkyl", "alkylthio", "haloalkylthio",
"alkylsulfinyl", "amino", "oxy", "thio", "alkylamino", "arylamino",
"aralkylamino", "arylsulfinyl", "arylsulfinylalkyl",
"arylsulfonyl", "arylsulfonylalkyl", "heteroarylsulfinyl",
"heteroarylsulfinylalkyl", "heteroaryl sulfonyl",
"heteroarylsulfonylalkyl", "heteroarylamino", "heteroaralkylamino",
"heteroaryloxy", "heteroaryloxylalkyl", "aryloxy", "aroyl",
"aralkanoyl", "aralkoxy", "aryloxyalkyl", "haloaryloxyalkyl",
"heteroaroyl", "heteroaralkanoyl", "heteroaralkoxy",
"heteroaralkoxyalkyl", "arylthio", "aryl thioalkyl", "alkoxyalkyl",
"acyl", "amidino", "guanidino", "dialkylsulfonium",
"trialkylphosphonium", and "dialkylsulfoniumalkyl" groups defined
above may optionally have 1 or more non-hydrido substituents such
as amidino, guanidino, dialkylsulfonium, trialkylphosphonium,
dialkylsulfoniumalkyl, perhaloaralkyl, aralkylsulfonyl,
aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl,
halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl,
cycloalkylsulfinylalkyl, cycloalkylsulfonyl,
cycloalkylsulfonylalkyl, heteroarylamino,
N-heteroarylamino-N-alkylamino, heteroaralkylamino, heteroaryloxy,
heteroaryloxylalkyl, haloalkylthio, alkanoyloxy, alkoxy,
alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy,
cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy,
cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy,
halocycloalkoxyalkyl, halocycloalkenyloxy,
halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, alkylamino,
alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio,
arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl,
alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl,
heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl,
alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl,
alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl
amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl,
arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl
amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio,
heteroarylsulfinyl, heteroarylsulfonyl, alkanoyl, alkenoyl, aroyl,
heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl,
alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy,
haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl,
cycloalkylalkyl, cycloalkenylalkyl, halo, haloalkyl, haloalkenyl,
haloalkoxy, hydroxyhaloalkyl. hydroxyaralkyl, hydroxyalkyl,
aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl,
aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially
saturated heterocyclyl, heteroaryl, heteroaryloxy,
heteroaryloxyalkyl, arylalkyl, heteroaralkyl, arylalkenyl,
heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarbonyl,
carboaralkoxy, carboxamido, carboxamidoalkyl, cyano,
carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono,
and diaralkoxyphosphonoalkyl.
[0672] The term "spacer" can include a covalent bond and a linear
moiety having a backbone of 1 to 7 contiguous atoms. The spacer may
have 1 to 7 atoms of a univalentor multi-valent chain. Univalent
chains may be constituted by a radical selected from .dbd.C(H)--,
.dbd.C(R.sup.2a)--, --O--, --S--, --S(O)--, --S(O).sub.2--, --NH--,
--N(R.sup.2a)--, --N.dbd., --CH(OH)--, .dbd.C(OH)--,
--CH(OR.sup.2a)--, .dbd.C(OR.sup.2a)--, and --C(O)-- wherein
R.sup.2a is selected from alkyl, alkenyl, alkynyl, aryl,
heteroaryl, aralkyl, aryloxyalkyl, alkoxyalkyl, alkylthioalkyl,
arylthioalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkenyl,
haloalkoxyalkyl, perhaloaralkyl, heteroarylalkyl,
heteroaryloxyalkyl, heteroarylthioalkyl, and heteroarylalkenyl.
Multi-valent chains may consist of a straight chain of 1 or 2 or 3
or 4 or 5 or 6 or 7 atoms or a straight chain of 1 or 2 or 3 or 4
or 5 or 6 atoms with a side chain. The chain may be constituted of
one or more radicals selected from:
[0673] alkylene, alkenyl, --O--, --O--CH.sub.2--, --S--CH.sub.2--,
--CH.sub.2CH.sub.2--, ethenyl, --CH.dbd.CH(OH)--, --OCH.sub.2O--,
--O(CH.sub.2).sub.2O--, --NHCH.sub.2--, --OCH(R.sup.2a)O--,
--O(CH.sub.2CHR.sup.2a)O--, --OCF.sub.2O--, --O(CF.sub.2).sub.2O--,
--S--, --S(O)--, --S(O).sub.2--, --N(H)--, --N(H)O--,
--N(R.sup.2a)O--, --N(R.sup.2a)--, --C(O)--, --C(O)NH--,
--C(O)NR.sup.2a--, --N.dbd., --OCH.sub.2--, --SCH.sub.2--,
S(O)CH.sub.2--, --CH.sub.2C(O)--, --CH(OH)--, .dbd.C(OH)--,
--CH(OR.sup.2a)--, .dbd.C(OR.sup.2a)--, S(O).sub.2CH.sub.2--, and
--NR CH.sub.2-- and many other radicals defined above or generally
known or ascertained by one of skill-in-the art. Side chains may
include substituents such as 1 or more non-hydrido substituents
such as amidino, guanidino, dialkylsulfonium, trialkylphosphonium,
dialkylsulfoniumalkyl, perhaloaralkyl, aralkylsulfonyl,
aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl,
halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl,
cycloalkylsulfinylalkyl, cycloalkylsulfonyl,
cycloalkylsulfonylalkyl, heteroarylamino,
N-heteroarylamino-N-alkylamino, heteroaralkylamino, heteroaryloxy,
heteroaryloxylalkyl, haloalkylthio, alkanoyloxy, alkoxy,
alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy,
cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy,
cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy,
halocycloalkoxyalkyl, halocycloalkenyloxy,
halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, alkylamino,
alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio,
arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl,
alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl,
heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl,
alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl,
alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl
amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl,
arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl
amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio,
heteroarylsulfinyl, heteroarylsulfonyl, alkanoyl, alkenoyl, aroyl,
heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl,
alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy,
haloalkylenedioxy, cycloalkyl, cycloalkenyl, cycloalkylalkyl,
cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,
hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl,
hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy,
aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated
heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl,
arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl,
carboxyalkyl, carboalkoxy, carboaralkoxy, carboxamido,
carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono,
phosphonoalkyl, diaralkoxyphosphono, and
diaralkoxyphosphonoalkyl.
[0674] Compounds of the present invention can exist in tautomeric,
geometric or stereoisomeric forms. The present invention
contemplates all such compounds, including cis- and trans-geometric
isomers, E- and Z-geometric isomers, R- and S-enantiomers,
diastereomers, d-isomers, I-isomers, the racemic mixtures thereof
and other mixtures thereof, as falling within the scope of the
invention. Pharmaceutically acceptable sales of such tautomeric,
geometric or stereoisomeric forms are also included within the
invention.
[0675] The terms "cis" and "trans" denote a form of geometric
isomerism in which two carbon atoms connected by a double bond will
each have a hydrogen atom on the same side of the double bond
("cis") or on opposite sides of the double bond ("trans").
[0676] Some of the compounds described contain alkenyl groups, and
are meant to include both cis and trans or "E" and "Z" geometric
forms.
[0677] Some of the compounds described contain one or more
stereocenters and are meant to include R, S, and mixtures of R and
S forms for each stereocenter present.
[0678] Some of the compounds described herein may contain one or
more ketonic or aldehydic carbonyl groups or combinations thereof
alone or as part of a heterocyclic ring system. Such carbonyl
groups may exist in part or principally in the "keto" form and in
part or principally as one or more "enol" forms of-each aldehyde
and ketone group present. Compounds of the present invention having
aldehydic or ketonic carbonyl groups are meant to include both
"keto" and "enol" tautomeric forms.
[0679] Some of the compounds described herein may contain one or
more amide carbonyl groups or combinations thereof alone or as part
of a heterocyclic ring system. Such carbonyl groups may exist in
part or principally in the "keto" form and in part or principally
as one or more "enol" forms of each amide group present. Compounds
of the present invention having amidic carbonyl groups are meant to
include both "keto" and "enol" tautomeric forms. Said amide
carbonyl groups may be both oxo (C.dbd.O) and thiono (C.dbd.S) in
type.
[0680] Some of the compounds described herein may contain one or
more imine or enamine groups or combinations thereof. Such groups
may exist in part or principally in the "imine" form and in part or
principally as one or more "enamine" forms of each group present.
Compounds of the present invention having said imine or enamine
groups are meant to include both "imine" and "enamine" tautomeric
forms.
[0681] Compounds of the present invention described herein are
1,4-quinones. 1,4-Quinone compounds, which can be considered to be
diketones of an arene compound and are well-known (for example, in
the simplest specific case where the parent aromatic compound is
benzene, the 1,4-quinone is 1,4-benzoquinone). 1,4-Quinones are
known to commonly undergo facile reduction to 1,4-hydroquinones via
both chemical and biochemical processes. A 1,4-hydroquinone is in
reality a 1,4-dihydroxyarene; in a specific case, the
1,4-hydroquinone of benzene is called 1,4-dihydoxybenzene or
1,4-benzoquinone. 1,4-Hydroquinones are also known to undergo
facile chemical or biochemical oxidation to the 1,4-quinones.
Interconversions of quinones to hydroquinones and vice versa
through oxidations and reductions are also well-known in the
chemical literature and in biological processes. 1,4-Quinone
compounds of the present invention having two carbonyls groups are
considered to encompass the corresponding 1,4-hydroquinone
compounds or forms.
[0682] The present invention also comprises a treatment and
prophylaxis in anticoagulant therapy for the treatment and
prevention of a variety of thrombotic conditions including coronary
artery and cerebrovascular disease in a subject, comprising
administering to the subject having such disorder a
therapeutically-effective amount of a compound of Formula (I):
55
[0683] or a pharmaceutically-acceptable salt thereof.
[0684] As a further embodiment, compounds of the present invention
of Formula (I) or a pharmaceutically-acceptable salt thereof as
defined above, comprise a treatment and prophylaxis of coronary
artery disease, cerebrovascular disease and other coagulation
cascade related disorders in a subject, comprising administering to
the subject having such disorder a therapeutically-effective amount
of compounds of formula (I) of the present invention or a
pharmaceutically-acceptable salt thereof.
[0685] Compounds of the present invention of Formula (I) or a
pharmaceutically-acceptable salt thereof can also be used whenever
inhibition of blood coagulation is required such as to prevent
coagulation of stored whole blood and to prevent coagulation in
other biological samples for testing or storage. Thus coagulation
inhibitors of the present inhibition can be added to or contacted
with stored whole blood and any medium containing or suspected of
containing plasma coagulation factors and in which it is desired
that blood coagulation be inhibited, e.g. when contacting the
mammal's blood with material selected from the group consisting of
vascular grafts, stents, orthopedic prothesis, cardiac prosthesis,
and extracorporeal circulation systems.
[0686] Compounds of Formula (I) are capable of inhibiting activity
of serine proteases related to the coagulation cascade, and thus
could be used in the manufacture of a medicament, a method for the
prophylactic or therapeutic treatment of diseases mediated by
coagulation cascade serine proteases, such as inhibiting the
formation of blood platelet aggregates, inhibiting the formation of
fibrin, inhibiting thrombus formation, and inhibiting embolus
formation in a mammal, in blood, in blood products, and in
mammalian organs. The compounds also can be used for treating or
preventing unstable angina, refractory angina, myocardial
infarction, transient ischemic attacks, atrial fibrillation,
thrombotic stroke, embolic stroke, deep vein thrombosis,
disseminated intravascular coagulation, ocular build up of fibrin,
and reocclusion or restenosis of recanalized vessels in a mammal.
The compounds also can be used to study the mechanism of action of
coagulation cascade serine proteases to enable the design of better
inhibitors and development of better assay methods. The compounds
of Formula (I) would be also useful in prevention of cerebral
vascular accident (CVA) or stroke.
[0687] Also included in the family of compounds of Formula (I) are
the pharmaceutically-acceptable salts thereof. The term
"pharmaceutically-acceptable salt" embraces salts commonly used to
form alkali metal salts and to form addition salts of free acids or
free bases. The nature of the salt is not critical, provided that
it is pharmaceutically acceptable. Suitable
pharmaceutically-acceptable acid addition salts of compounds of
Formula (I) may be prepared from inorganic acid or from an organic
acid. Examples of such inorganic acids are hydrochloric,
hydrobrornic, hydroiodic, nitric, carbonic, sulfuric and phosphoric
acid. Appropriate organic acids may be selected from aliphatic,
cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and
sulfonic classes of organic acids, examples of which are formic,
acetic, propionic, succinic, glycolic, gluconic, lactic, malic,
tartaric, citric, ascorbic, glucoronic, maleic, fumaric, pyruvic,
aspartic, glutamic, benzoic, anthranilic, mesylic, salicylic,
p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic),
methanesulfonic, ethylsulfonic, benzenesulfonic, sulfanilic,
stearic, cyclohexylaminosulfonic, algenic, galacturonic acid.
Suitable pharmaceutically-acceptable base addition salts of
compounds of Formula (I) include metallic salts made from aluminum,
calcium, lithium, magnesium, potassium, sodium and zinc or organic
salts made from N,N'-dibenzylethyleneldiamine, choline,
chloroprocaine, diethanolamine, ethylenediamine, meglumine
(N-methylglucamine) and procain. All of these salts may be prepared
by conventional means from the corresponding compound of Formula
(I) by reacting, for example, the appropriate acid or base with the
compound of Formula (I).
[0688] The present invention also comprises a pharmaceutical
composition comprising a therapeutically-effective amount of a
compound of Formulas (I) in association with at least one
pharmaceutically-acceptable carrier, adjuvant or diluent.
Pharmaceutical compositions of the present invention can comprise
the active compounds of Formula (I) in association with one or more
non-toxic, pharmaceutically-acceptable carriers and/or diluents
and/or adjuvants (collectively referred to herein as "carrier"
materials) and, if desired, other active ingredients. The active
compounds of the present invention may be administered by any
suitable route, preferably in the form of a pharmaceutical
composition adapted to such a route, and in a dose effective for
the treatment intended.
[0689] The active compounds and composition may, for example, be
administered orally, intravascularly, intraperitoneally,
subcutaneously, intramuscularly, oculary, or topically. For
treating ocular build up of fibrin, the compounds may be
administered intraocularly or topically as well as orally or
parenterally.
[0690] The compounds can be administered in the form of a depot
injection or implant preparation which may be formulated in such a
manner as to permit a sustained release of the active ingredient.
The active ingredient can be compressed into pellets or small
cylinders and implanted subcutaneously or intramusculary as depot
injections or implants. Implants may employ inert materials such as
biodegradable polymers or synthetic silicones, for example,
Silastic, silicone rubber or other silicon containing polymers.
[0691] The compounds can also be administered in the form of
liposome delivery systems, such as small unilamellar vesicles,
large unilamellar vesicles and multilamellar vesicles. Liposomes
can be formed from a variety of phospholipids, such as cholesterol,
stearylamine or phosphatidylcholines.
[0692] The compounds may also be delivered by the use of monoclonal
antibodies as individual carriers to which the compound molecules
are coupled. The compounds may also be coupled with soluble
polymers as targetable drug carriers. Such polymers can include
polyvinylpyrrolidone, pyran copolymer,
polyhydroxy-propyl-methacrylamide-phenol,
polyhydroxyethyl-aspartamide-phenol, or
ployethyleneoxide-polylysine substituted with palmitoyl residues.
Furthermore, the compounds may be coupled to a class of
biodegradable polymers useful in achieving controlled release of a
drug, for example, polylactic acid, polyglycolic acid, copolymers
of polylactic and polyglycolic acid, polyepsilon caprolactone,
polyhydroxy butyric acid, polyorthoesters, polyacetals,
polydihydropyrans, polycyanoacrylates and cross linked or
amphitpathic block copolymers of hydrogels.
[0693] For oral administration, the pharmaceutical composition may
be in the form of, for example, tablets, capsules (each of which
includes sustained release or timed release formulations), pills,
powders, granules, elixers, tinctures, suspensions, liquids
including syrups, and emulsions. The pharmaceutical composition is
preferably made in the form of a dosage unit containing a
particular amount of the active ingredient. Examples of such dosage
units are tablets or capsules. The active ingredient may also be
administered by injection as a composition wherein, for example,
saline, dextrose or water may be used as a suitable carrier.
[0694] The amount of therapeutically active compounds which are
administered and the dosage regimen for treating a disease
condition with the compounds and/or compositions of this invention
depends on a variety of factors, including the age, weight, sex and
medical condition of the subject, the severity of the disease, the
route and frequency of administration, and the particular compound
employed, and thus may vary widely.
[0695] The pharmaceutical compositions may contain active
ingredients in the range of about 0.1 to 2000 mg, and preferably in
the range of about 0.5 to 500 mg. A daily dose of about 0.01 to 100
mg/kg body weight, and preferably between about 0.5 and about 20
mg/kg body weight, may be appropriate. The daily dose can be
administered in one to four doses per day.
[0696] The compounds may be formulated in topical ointment or
cream, or as a suppository, containing the active ingredients in a
total amount of, for example, 0.075 to 30% w/w, preferably 0.2 to
20% w/w and most preferably 0.4 to 15% w/w. When formulated in an
ointment, the active ingredients may be employed with either
paraffinic or a water-miscible ointment base.
[0697] Alternatively, the active ingredients may be formulated in a
cream with an oil-in-water cream base. If desired, the aqueous
phase of the cream base may include, for example at least 30% w/w
of a polyhydric alcohol such as propylene glycol, butane-1,3-diol,
mannitol, sorbitol, glycerol, polyethylene glycol and mixtures
thereof. The topical formulation may desirably include a compound
which enhances absorption or penetration of the active ingredient
through the skin or other affected areas. Examples of such dermal
penetration enhancers include dimethylsulfoxide and related
analogs. The compounds of this invention can also be administered
by a transdermal device. Preferably topical administration will be
accomplished using a patch either of the reservoir and porous
membrane type or of a solid matrix variety. In either case, the
active agent is delivered continuously from the reservoir or
microcapsules through a membrane into the active agent permeable
adhesive, which is in contact with the skin or mucosa of the
recipient. If the active agent is absorbed through the skin, a
controlled and predetermined flow of the active agent is
administered to the recipient. In the case of microcapsules, the
encapsulating agent may also function as the membrane.
[0698] The oily phase of the emulsions of this invention may be
constituted from known ingredients in a known manner. While the
phase may comprise merely an emulsifier, it may comprise a mixture
of at least one emulsifier with a fat or an oil or with both a fat
and an oil. Preferably, a hydrophilic emulsifier is included
together with a lipophilic emulsifier which acts as a stabilizer.
It is also preferred to include both an oil and a fat. Together,
the emulsifier(s) with or without stabilizer(s) make-up the
so-called emulsifying wax, and the wax together with the oil and
fat make up the so-called emulsifying ointment base which forms the
oily dispersed phase of the cream formulations. Emulsifiers and
emulsion stabilizers suitable for use in the formulation of the
present invention include Tween 60, Span 80, cetostearyl alcohol,
myristyl alcohol, glyceryl monostearate, and sodium lauryl sulfate,
among others.
[0699] The choice of suitable oils or fats for the formulation is
based on achieving the desired cosmetic properties, since the
solubility of the active compound in most oils likely to be used in
pharmaceutical emulsion formulations is very low. Thus, the cream
should preferably be a non-greasy, non-staining and washable
product with suitable consistency to avoid leakage from tubes or
other containers. Straight or branched chain, mono- or dibasic
alkyl esters such as diisoadipate, isocetyl stearate, propylene
glycol diester of coconut fatty acids, isopropyl myristate, decyl
oleate, isopropyl palmitate, butyl stearate, 2-ethylhexyl
palmintate or a blend of branched chain esters may be used. These
may be used alone or in combination depending on the properties
required. Alternatively, high melting point lipids such as white
soft paraffin and/or liquid paraffin or other mineral oils can
be-used.
[0700] For therapeutic purposes, the active compounds of the
present invention are ordinarily combined with one or more
adjuvants appropriate to the indicated route of administration. If
administered per os, the compounds may be admixed with lactose,
sucrose, starch powder, cellulose esters of alkanoic acids,
cellulose alkyl esters, talc, stearic acid, magnesium stearate,
magnesium oxide, sodium and calcium salts of phosphoric and
sulfuric acids, gelatin, acacia gum, sodium alginate,
polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted
or encapsulated for convenient administration. Such capsules or
tablets may contain a controlled-release formulation as may be
provided in a dispersion of active compound in hydroxypropylmethyl
cellulose. Formulations for parenteral administration may be in the
form of aqueous or non-aqueous isotonic sterile injection solutions
or suspensions. These solutions and suspensions may be prepared
from sterile powders or granules having one or more of the carriers
or diluents mentioned for use in the formulations for oral
administration. The compounds may be dissolved in water,
polyethylene glycol, propylene glycol, ethanol, corn oil,
cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium
chloride, and/or various buffers. Other adjuvants and modes of
administration are well and widely known in the pharmaceutical
art
[0701] In practicing the methods of the present invention for the
treatment and prevention of a variety of thrombotic conditions
including coronary artery and cerebrovascular disease, the
compounds and pharmaceutical compositions of the present invention
are administered alone or in combination with one another, or in
combination with other therapeutics or in vivo diagnostic agents.
The coagulation cascade inhibitors of the present invention can
also be co-administered with suitable anti-platelet agreggation
agents, including, but not limited to ticlopidine or clopidrogel,
fibrinogen receptor antagonists (e.g. to treat or prevent unstable
angina or to prevent reocculsion after angioplasty and restenosis),
anti-coagulants such as aspirin, warfarin or heparins, thrombolytic
agents such as plasminogen activators or streptokinase to achieve
synergistic effects in the treatment of various pathologies, lipid
lowering agents including antihypercholesterolemics (e.g. HMG CoA
reductase inhibitors such as mevastatin, lovastatin, simvastatin,
pravastatin, and fluvastatin, HMG CoA synthatase inhibitors, etc.),
anti-diabetic drugs, or other cardiovascular agents (loop
diuretics, thiazide type diuretics, nitrates, aldosterone
antagonistics (i.e., spironolactone and epoxymexlerenone),
angiotensin converting enzyme (e.g. ACE) inhibitors, angiotensin II
receptor antagonists, beta-blockers, antiarrhythmics,
anti-hypertension agents, and calcium channel blockers) to treat or
prevent atherioscierosis. For example, patients suffering from
coronary artery disease, and patients subjected to angioplasty
procedures, would benefit from coadministration of fibrinogen
receptor antagonists and coagulation cascade inhibitors of the
present invention. Also, coagulation cascade inhibitors could
enhance the efficiency of tissue plasminogen activator-mediated
thrombolytic reperfusion.
[0702] Typical doses of coagulation cascade inhibitors of the
present invention with other suitable anti-platelet agents,
anticoagulation agents, cardiovascular therapeutic agents, or
thrombolytic agents may be the same as those doses of coagulation
cascade inhibitors administered without coadministration of
additional anti-platelet agents, anticoagulation agents,
cardiovascular therapeutic agents, or thrombolytic agents, or may
be substantially less than those doses of coagulation cascade
inhibitors administered without coadministration of additional
anti-platelet agents, anticoagulation agents, cardiovascular
therapeutic agents, or thrombolytic agents, depending on a
patient's therapeutic needs.
[0703] The present novel methods preferably employ compounds which
selectively inhibit human TF-VIIA over the inhibition of both human
Thrombin II and human factor Xa. Preferably, the compounds have a
human TF-VIIA IC.sub.50 of less than 0.5 .mu.M and also have a
selectivity ratio of TF-VIIA inhibition over both human Thrombin II
and human factor Xa inhibition of at least 10, and more preferably
at least 100. Even more preferably, the compounds have a human
TF-VIIA IC.sub.50 of less than 0.1 .mu.M and also have a
selectivity ratio of TF-VIIA inhibition over both human Thrombin II
and human factor Xa inhibition of at least 1000, and most
preferably at least 10,000.
[0704] All mentioned references are incorporated by reference as if
here written.
[0705] Although this invention has been described with respect to
specific embodiments, the details of these embodiments are not to
be construed as limitations. The following examples are provided to
illustrate the present invention and are not intended to limit the
scope thereof. Without further elaboration, it is believed that one
skilled in the art can, using the preceding descriptions, utilize
the present invention to its fullest extent. Therefore the
following preferred specific embodiments are to be construed as
merely illustrative and not limitative of the remainder of the
disclosure in any way whatsoever. Compounds containing multiple
variations of the structural modifications illustrated in the
schemes or the following Examples are also contemplated. Those
skilled in the art will readily understand that known variations of
the conditions and processes of the following preparative
procedures can be used to prepare these compounds.
[0706] One skilled in the art may use these generic methods to
prepare the following specific examples, which have been or may be
properly characterized by .sup.1H NMR, mass spectrometry, elemental
composition, and similar procedures. These compounds also may be
formed in vivo. The following examples contain detailed
descriptions of the methods of preparation of compounds of Formula
(I). These detailed descriptions fall within the scope and are
presented for illustrative purposes only and are not intended as a
restriction on the scope of the invention. All parts are by weight
and temperatures are Degrees centigrade unless otherwise
indicated.
[0707] The following general synthetic sequences are useful in
making the present invention. Abbreviations used in the schemes and
tables include: "AA" represents amino acids, "AcCN" represents
acetonitrile, "AcOH" represents acetic acid, "BINAP" represents
2,2'-bis(diphenylphosphino)-1,- 1'-binaphthyl, "BnOH" represents
benzyl alcohol, "BnCHO" represents 2-phenylethanal," BnSO.sub.2Cl"
represents benzylsulfonyl chloride, "Boc" represents
tert-butyloxycarbonyl, "BOP" represents
benzotriazol-1-yl-oxy-tris-(dimethylamino), "bu" represents butyl,
"dba" represents dibenzylidene-acetone, "DCC" represents
1,3-dicyclohexylcarbodiimide, "DCM" represents dichloromethane or
methylene chloride, "DIBAH" or "DIBAL" represents
diisobutylaluminum hydride, "DMF" represents dimethylformamide,
"DMSO" represents dimethylsulfoxide, "DPPA" represents
diphenylphosphoryl azide", "EDC" represents
1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride, "Ex.
No." represents Example Number, "Fmoc" represents
9-fluorenylmethoxycarbonyl, "HOBt" represents
hydroxybenzoltriazole", "LDA" represents lithium diisopropylamide,
"MCPBA" represents meta-chloroperbenzoic acid, "MW" represents
molecular weight, "NMM" represents N-methylmorpholine, "Ph"
represents phenyl or aryl, "PHTH" represents a phthaloyl group,
"pnZ" represents 4-nitrobenzyloxy-carbonyl, "FITC" represents a
phase transfer catalyst, "py" represents pyridine, "RNH.sub.2"
represents a primary organic amine, "p-TsOH" represents
paratoluenesulfonic acid, "TBAF" represents tetrabutylammonium
fluoride, "TBTU" represents
2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyl uronium
tetrafluoroborate, "TEA" represents triethylamine, "TFA" represents
trifluoroacetic acid, "THF" represents tetrahydrofuran, "TMS"
represents trimethylsilyl, "TMSCN" represents trimethylsilyl
cyanide, and "Cbz" or "Z" represents benzyloxycarbonyl.
GENERAL SYNTHETIC PROCEDURES AND SPECIFIC EXAMPLES
[0708] The 1,4-quinone compounds of the present invention can be
synthesized, for example, according to the following procedures and
Schemes given below. 56 57 58 59 60 61
[0709] Schemes 1, 2, 3, 4, 5, and 6 above summarize generic
procedures that permit the preparation of a wide variety of the
compounds of the present invention through the ability to introduce
numerous R.sup.2 substituents represented by Z.degree.-Q wherein
Z.degree. is a single bond, a wide variety of amino substituting
groups represented by B--, B--CH.sub.2, B--CO, and B--SO.sub.2, and
a large number of amide forming Y groups at the carboxylic acid
group in which E.degree. is C(O)NH. Examples 1, 2, and 3 below
shows the preparation of a compound wherein X.degree. is hydrido
although other substituents can be present at this position. 62
[0710] Triethylamine (3.46 mL, 24.8 mmol) was added to a solution
of the appropriate phenol (5.0 g, 20.7 mmol) and triflic anhydride
(4.18 mL, 24.8 mmol) in dichloromethane at -10.degree. C. After
stirring at room temperature for 3 hours, the solution was
acidified with 2N hydrochloric acid and extracted with
dichloromethane. The organic layer was washed with brine, dried
over magnesium sulfate, and filtered. The solvent was removed by
evaporation to afford the crude product. The product was purified
by column chromatography (15% ethyl acetate-hexane) to afford 5.53
g (72%) of a clear oil of product EX-1A; .sup.1H NMR ppm: 3.78 (s,
3H), 3.87 (d, 2H), 3.96 (s, 3H), 7.27 (d, 1H, J =9.2 Hz), 7.95 (d,
1H, J=9.2 Hz); .sup.19F NMR ppm: -73.89 (s, 3F); HPLC purity
(retention time): >99% (3.62 min); HRMS calcd for
C.sub.11H.sub.10O.sub.8N.sub.1F- .sub.3 (M.sup.++NH.sub.4)
391.0423, found 391.0396. 63
[0711] The triflate compound EX-1A (5.53 g, 14.8 mmol) was added to
a solution of tri-n-butylphenylstannane (5.8 mL, 17.7 mmol),
lithium chloride (1.9 g, 44.8 mmol), and
tetrakis(triphenylphosphine)palladium(0) (34.0 mg, 0.29 mmol) in 74
mL of anhydrous dioxane. The solution was heated to 85.degree. C.
for 18 hours. The organic layer was washed with brine, dried over
magnesium sulfate, and filtered. The solvent was removed by
evaporation to afford the crude product. The product was purified
by column chromatography (15% ethyl acetate-hexane) to afford 3.32
g (74%) of a white solid of product EX-1B; .sup.1H NMR ppm: 3.69
(s, SH), 3.94 (s, 3H), 7.17 (d, 1H, J=8.3 Hz), 7.29 (m, 2H), 7.45
(m, 3H), 7.89 (d, 1H, J=8.3 Hz); HPLC purity (retention time):
>99% (3.60 min); HRMS calcd for C.sub.16H.sub.15O.sub.5N.sub.1
(M.sup.++NH.sub.4) 319.1294, found 319.1312. 64
[0712] A catalytic amount of palladium on carbon (5%) in dioxane
was added to the nitro compound EX-1B (3.3 g, 11.0 mmol) in a 1:1
mixture of methanol and dioxane. The mixture was hydrogenated on a
Parr Hydrogenator (50 psi, room temperature) until hydrogen uptake
stopped (4 hrs). The mixture was filtered through celite and the
solvent was removed to afford the product. The product EX-1C was
not purified and carried on to the next step. HPLC purity
(retention time): 96.5% (2.03 min). 65
[0713] Sodium triacetoxyborohydride (9.3 g, 43.0 mmol) was added to
a solution of the aniline EX-1C (2.99 g, 11.0 mmol), acetone (1.0
mL, 13.6 mmol), and a drop of acetic acid in a
tetrahydrofuran-dichloromethane (1:1) solution. After stirring at
room temperature for 14 hours, additional acetone (1.0 mL, 13.6
mmol) and acetic acid (excess) was added, and the solution stirred
at room temperature for 18 hours. The solution was diluted with
ether and water. The organic layer was washed with brine, dried
over magnesium sulfate, and filtered. The solvent was removed by
evaporation to afford the crude product. The product was purified
by column chromatography (15% ethyl acetate-hexane) to afford 3.55
g (100%) of a yellow oil of product EX-1D; .sup.1H NMR ppm: 1.24
(d, 6H), 3.59 (s, 3H), 3.62 (m, 2H), 3.72 (s, 3H), 4.09 (m, 1H),
6.62 (d, 1H, J=8.3 Hz), 6.92 (d, 1H, J=8.3 Hz), 7.28 (m, 5H); HPLC
purity (retention time): 97.5% (2.57 min). 66
[0714] Aqueous sodium hydroxide (10%) (7.6 mL, 19.0 mmol) was added
to a solution of the methyl ester EX-1D (1.51 g, 4.81 mmol) in
methanol and the resulting solution stirred at 60.degree. C. for 3
hours. The solution was acidified with 2 N hydrochloric acid and
extracted with diethyl ether. The solution was washed with brine,
dried over magnesium sulfate, and filtered. The solvent was removed
by evaporation to afford the crude product. The product was
purified by column chromatography (40% ethyl acetate-hexane) to
afford 0.44 g (31%) of a white solid of product EX-1E; .sup.1H NMR
ppm: 1.25 (d, 6H), 3.62 (m, 3H), 3.75 (s, 3H), 6.50 (d, 1H, J=8.3
Hz), 6.94 (d, 1H, J=8.3 Hz), 7.27 (m, 5H); HPLC purity (retention
time): >99% (2.11 min). 67
[0715] PS-carbodiimide (1.00 mmol/g) (2.8 g, 2.8 mmol) was added to
a slurry of the acid EX-1E (0.42 g, 1.4 mmole),
1-hydroxybenzotriazole (0.19 mg, 1.4 mmol), the Cbz-amine (0.54 g,
1.6 mmol), and N-methylmorpholine (620 uL, 5.6 mmol) in a
dichloromethane-dimethylformam- ide (3:1) solution, and the
suspension was agitated for 18 hours. Upon completion of the
reaction, the polyamine resin (2.81 mmol/g) (1.0 g, 2.8 mmol) and
polymer-bound aldehyde (2.3 mmol/g) (1.0 g, 2.30 mmol) were added,
and the suspension was agitated for 1 hour. The solution was
filtered, and the polymer was rinsed with dimethylformamide and
dichloromethane until no more UV activity was seen in the
dichloromethane washing. The combined filtrate and washings were
evaporated to afford the crude product. The product was purified by
column chromatography (60% ethyl acetate-hexane), stuck to the
column, and was washed off with 100% ethyl acetate to afford 0.73 g
(92%) of a white solid of product EX-1F; .sup.1H NMR ppm: 1.25 (d,
6H), 3.62 (m, 3H), 3.71 (s, 3H), 4.33 (d, 2H), 5.19 (s, 2H), 6.05
(bt, 1H), 6.63 (d, 2H, J =8.3 Hz), 6.93 (d, 2H, J=8.3 Hz), 7.29 (m,
13H), 7.77 (d, 2H); HPLC purity (retention time): >99% (2.55
min). 68
[0716] Boron tribromide 1M (2.7 mL, 2.7 mmol) was added to a
solution of the ether EX-1F (0.50 g, 0.88 mmol) in dichloromethane
at -10.degree. C. The solution stirred at -10.degree. C for 1.5
hours. The solution was quenched with water and evaporated to a
minimal amount of solvent. The crude product mixture was purified
directly by reverse-phase chromatography to afford a mixture of two
products. Fraction one of reverse-phase chromatography afforded
0.22 g (60%) of a purple-white solid of product EX-1G; .sup.1H NMR
ppm: 1.41 (d, 6H), 3.68 (s, 2H), 3.89 (m, 1H), 4.28 (s, 2H), 6.97
(m, 1H), 7.25-7.92 (m, 11H); HPLC purity (retention time): >99%
(1.42 min).
[0717] A solution of potassium nitrosodisulfonate (Fremy's salt)
(0.15 g, 0.56 mmol) in 5 mL of water was added to a solution of the
phenol EX-1G (76.9 mg, 0.18 mmol) in 5 mL of dioxane. The solution
stirred at room temperature for 2 hours (turning deep red-brown).
The solvent was removed by evaporation to afford the crude product.
The product was purified by reverse phase chromatography to afford
4.2 mg (54%) of a purple solid of product; HPLC purity (retention
time): 85% (1.75 min). 69
[0718] Sodium triacetoxyborohydride (2.8 g, 13.2 mmol) was added to
a solution of the aniline prepared in Example 1 (EX-1C) (0.89 g,
3.3 mmol), phenylacetaldehyde (540 uL, 39.2 mmol), and a drop of
acetic acid in a tetrahydrofuran-dichloromethane-(1:1) solution.
After stirring at room temperature for 2 hours, the solution was
diluted with dichloromethane and water. The organic layer was
washed with brine, dried over magnesium sulfate, and filtered. The
solvent was removed by evaporation to afford the crude product. The
product was purified by column chromatography (25% ethyl
acetate-hexane) to afford 0.69 g (56%) of a yellow oil of product
EX-2A; .sup.1H NMR ppm: 3.04 (t, 2H), 3.50 (t, 2H), 3.69 (s, 3H),
3.67 (s, 2H), 3.69 (s, 3H), 6.75 (d, 1H, J=8.3 Hz), 7.02 (d, 1H,
J=8.3 Hz), 7.35 (m, 10H); HPLC purity (retention time): >99%
(4.37 min); HRMS calcd for C.sub.24H.sub.25O.sub.3N.sub.1
(M.sup.++H) 376.1913, found 376.1872. 70
[0719] Aqueous sodium hydroxide (10%) (2.9 mL, 7.2 mmol) was added
to a solution of the methyl ester EX-2A (0.69 g, 1.8 mmol) in
methanol and the resulting solution stirred at 60.degree. C. for 5
hours. The solution was acidified with 2 N hydrochloric acid and
extracted with diethyl ether. The solution was washed with brine,
dried over magnesium sulfate, and filtered. The solvent was removed
by evaporation to afford 0.66 g (100%) of an orange foam of product
EX-2B; HPLC purity (retention time): 80% (3.83 min). 71
[0720] 1-Hydroxybenzotriazole (247 mg, 1.8 mmol) was added to a
slurry of the acid EX-2B (0.66 g, 1.83 mmole) and PS-carbodiimide
(1.00 mmol/g) (3.6 g, 3.6 mmol) in a
dichloromethane-dimethylformamide (3:1) solution. The suspension
was agitated for 15 minutes. The Cbz-amine (0.70 g, 2.2 mmol) and
N-methylmorpholine (1.0 mL, 9.0 mmol) was added and the suspension
was agitated for 18 hours. Upon completion of the reaction, the
polyamine resin (2.81 mmol/g) (1.0 g, 2.81 mmol) and polymer-bound
aldehyde (2.3 mmol/g) (1.0 g, 2.30 mmol) were added and the
suspension was agitated for 1 hour. The solution was filtered, and
the polymer was rinsed with dimethylformamide and dichloromethane
until no more UV activity was seen in the dichloromethane washing.
The combined filtrate and washings were evaporated to afford the
product. The product was purified by column chromatography (60%
ethyl acetate-hexane) to afford 0.52 g (45%) of a white solid of
product EX-2C; .sup.1H NMR ppm: 3.17 (m, 2H), 3.65 (m, 2H), 3.77
(s, 2H), 3.86 (s, 3H), 4.64 (d, 2H), 5.27 (bt, 1H), 4.40 (s, 2H),
6.96 (d, 1H), 7.11 (d, 1H), 7.56 (m, 16H), 8.23 (m, 3H), 8.41 (bt,
1H), 9.40 (bs, 1H), 9.75 (bs, 1H); HPLC purity (retention time):
>99% (3.80 min); HRMS calcd for C.sub.39H.sub.38O.sub.4N.sub.4
(M.sup.++H) 627.2971, found 627.2918. 72
[0721] Boron tribromide 1M (1.1 mL, 1.0 mmol) was added to a
solution of the ether EX-2C (0.22 g, 0.36 mmol) in dichloromethane
at -10.degree. C. The solution stirred at -10.degree. C. for 35
hours. The solution was quenched with water and evaporated to a
minimal amount of solvent. The crude product mixture was purified
directly by reverse-phase chromatography to afford 0.10 g (60%) of
a white solid of product EX-2D; .sup.1H NMR ppm: 3.12 (t, 2H), 3.66
(m, 4H), 4.51 (s, 2H), 6.96 (d, 1H), 7.36 (m, 12H), 7.55 (d, 2H),
7.80 (d, 2H); HPLC purity (retention time): 92% (2.53 min); HRMS
calcd for C.sub.30H.sub.30O.sub.2N.sub.4 (M.sup.++H) 479.2447,
found 479.2446.
[0722] A solution of potassium nitrosodisulfonate (Fremy's salt)
(0.15 g, 0.56 mmol) in 5 mL of water was added to a solution of the
phenol EX-2D (100 mg, 0.23 mmol) in 5 mL of THF. The solution
stirred at room temperature for 2 hours (turning deep red-brown).
The solvent was removed by evaporation to afford the crude product.
The product was purified by reverse phase chromatography to afford
3.0 mg (2%) of a purple solid of product; HPLC purity (retention
time): 89% (1.52 min). 73
[0723] Using the process of Example 1 and tributyl
3-(2-trimethylsilyletho- xy-carbonylamido)phenylstannane in place
of tributylphenylstannane, the compound of Example 3 is
prepared.
[0724] Using the examples and methods described herein previously,
the following examples having a amidinoaralkyl or
amidinoheteroaralkyl type Y.sup.0 group could be prepared:
[0725]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-aminophenyl]-6-[N,N-
-dimethylhydrazino]-1,4-benzoquinonyl]]acetamide;
[0726]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-aminophenyl]-6-[N-e-
thyl-N-methylhydrazino]-1,4-benzoquinonyl]]acetamide;
[0727]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-aminophenyl]-5-chlo-
ro-6-[N,N-dimethylhydrazino]-1,4-benzoquinonyl]]acetamide;
[0728]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-aminophenyl]-5-chlo-
ro-6-[N-ethyl-N-methylhydrazino]-1,4-benzoquinonyl]]acetamide;
[0729]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3,5-diaminophenyl]-6--
[N,N-dimethylhydrazino]-1,4-benzoquinonyl]]acetamide;
[0730]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3,5-diaminophenyl]-6--
[N-ethyl-N-methylhydrazino]-1,4-benzoquinonyl]]acetamide;
[0731]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3,5-diaminophenyl]-5--
chloro-6-[N,N-dimethylhydrazino]-1,4-benzoquinonyl]]acetamide;
[0732]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3,5-diaminophenyl]-5--
chloro-6-[N-ethyl-N-methylhydrazino]-1,4-benzoquinonyl]]acetamide;
[0733]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-carboxyphen-
yl]-6-[N,N-dimethylhydrazino]-1,4-benzoquinonyl]]acetamide;
[0734]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-carboxyphen-
yl]-6-[N-ethyl-N-methylhydrazino]-1,4-benzoquinonyl]]acetamide;
[0735]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-carboxyphen-
yl]-5-chloro-6-[N,N-dimethylhydrazino]-1,4-benzoquinonyl]]acetamide;
[0736]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-carboxyphen-
yl]-5-chloro-6-[N-ethyl-N-methylhydrazino]-1,4
-benzoquinonyl]]acetamide;
[0737]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-(N-benzylam-
idocarbonyl)phenyl]-6-[N,N-dimethylhydrazino1,4-benzoquinonyl]]acetamide;
[0738]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-(N-benzylam-
idocarbonyl)phenyl]-6-[N-ethyl-N-methylhydrazino]-1,4-benzoquinonyl]]aceta-
mide;
[0739]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-(N-benzylam-
idocarbonyl)phenyl]-5-chloro-6-[N,N-dimethylhydrazino]-1,4-benzoquinonyl]]-
acetamide;
[0740]
2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-33-amino-5-(N-benzylamid-
ocarbonyl)phenyl]-5-chloro-6-[N-ethyl-N-methylhydrazino]-1,4
-benzoquinonyl]]acetamide.
[0741] Using the examples and methods described herein previously,
the following further examples having a amidinoaralkyl or
amidinoheteroaralkyl type Y.sup.0 group could be prepared of the
formula: 74
[0742] wherein B, A, R.sup.2, X.sup.o, and Y.sup.0 are selected to
form the following compounds:
[0743] R.sup.2 is 3-aminophenyl, B is phenyl, A is CH.sub.2,Y.sup.0
is 4-amidinobenzyl, and X.sup.0 is chloro;
[0744] R.sup.2 is 3-aminophenyl, B is 3-chlorophenyl, A is
CH.sub.2CH.sub.2,Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro;
[0745] R.sup.2 is 3-aminophenyl, B is phenyl, A is CH.sub.2,Y.sup.0
is 4-amidinobenzyl, and X.sup.0 is hydrido;
[0746] R.sup.2 is 3-aminophenyl, B is 2-imidazoyl, A is
CH.sub.2CH.sub.2CH.sub.2,Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro;
[0747] R.sup.2 is 3-amidocarbonyl-5-aminophenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is chloro;
[0748] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2,Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is chloro;
[0749] R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2,Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is chloro;
[0750] R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2,Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is chloro;
[0751] R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phe- nyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2,Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is chloro;
[0752] R.sup.2 is 3,5-diaminophenyl, B is 3-chlorophenyl, A is
CH.sub.2CH.sub.2,Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro;
[0753] R.sup.2 is 3-amino-5-carboxyphenyl, B is 3-chlorophenyl, A
is CH.sub.2CH.sub.2,Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro;
[0754] R.sup.2 is 3-amidocarbonyl-5-aminophenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is hydrido;
[0755] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2,Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is hydrido;
[0756] R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2 Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is hydrido;
[0757] R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2,Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is hydrido;
[0758] R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phe- nyl, B is
3-chlorophenyl, A is CH.sub.2CH.sub.2,Y.sup.0 is 4-amidinobenzyl,
and X.sup.0 is hydrido;
[0759] R.sup.2 is 3,5-diaminophenyl, B is 3-chlorophenyl, A is
CH.sub.2CH.sub.2,Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
hydrido;
[0760] R.sup.2 is 3-amino-5-carboxyphenyl, B is 3-chlorophenyl, A
is CH.sub.2CH.sub.2,Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
hydrido;
[0761] R.sup.2 is 3-aminophenyl, B is 2,2,2-trifluoroethyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0762] R.sup.2 is 3-aminophenyl, B is (S)-2-butyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0763] R.sup.2 is 5-amino-2-fluorophenyl, B is isopropyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0764] R.sup.2 is 2-methyl-3-aminophenyl, B is isopropyl, A is a
bond, Y.sup.0is 4-amidinobenzyl, and X.sup.0 is chloro;
[0765] R.sup.2 is 3-aminophenyl, B is ethyl, A is a bond, Y.sup.0
is 4-amidinobenzyl, and X.sup.0 is chloro;
[0766] R.sup.2 is 3-aminophenyl, B is ethyl, A is a bond, Y.sup.0
is 4-amidino-2-fluorobenzyl, and X.sup.0 is chloro;
[0767] R.sup.2 is 3-aminophenyl, B is 2-propenyl, A is a bond,
Y.sup.0is 4-amidinobenzyl, and X.sup.0 is chloro;
[0768] R.sup.2 is 3-aminophenyl, B is isopropyl, A is a bond,
Y.sup.0 is 4-amidino-2-fluorobenzyl, and X.sup.0 is chloro;
[0769] R.sup.2 is 3-aminophenyl, B is isopropyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0770] R.sup.2 is 3-aminophenyl, B is 2-butyl, A is a bond, Y.sup.0
is 4-amidinobenzyl, and X.sup.0 is chloro;
[0771] R.sup.2 is 3-aminophenyl, B is (R)-2-butyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0772] R.sup.2 is 3-aminophenyl, B is 2-propynyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0773] R.sup.2 is 3-aminophenyl, B is 3-pentyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is hydrido;
[0774] R.sup.2 is 3-aminophenyl, B is hydrido, A is
CH.sub.2,Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0775] R.sup.2 is 3-aminophenyl, B is ethyl, A is CH.sub.2,Y.sup.0
is 4-amidinobenzyl, and X.sup.0 is chloro;
[0776] R.sup.2 is 3-aminophenyl, B is 2-methypropyl, A is a bond,
Y.sup.0is 4-amidinobenzyl, and X.sup.0 is chloro;
[0777] R.sup.2 is 3-aminophenyl, B is 2-propyl, A is CH.sub.3CH,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0778] R.sup.2 is 3-aminophenyl, B is propyl, A is a bond, Y.sup.0
is 4-amidino-2-fluorobenzyl, and X.sup.0 is chloro;
[0779] R.sup.2 is 3-aminophenyl, B is 6-amidocarbonylhexyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0780] R.sup.2 is 3-aminophenyl, B is tert-butyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is hydrido;
[0781] R.sup.2 is 3-aminophenyl, B is tert-butyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0782] R.sup.2 is 3-aminophenyl, B is 3-hydroxypropyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0783] R.sup.2 is 3-aminophenyl, B is 2-methylpropyl, A is a bond,
Y.sup.0is 4-amidino-2-fluorobenzyl, and X.sup.0 is chloro;
[0784] R.sup.2 is 3-aminophenyl, B is butyl, A is a bond, Y.sup.0
is 4-amidinobenzyl, and X.sup.0 is chloro;
[0785] R.sup.2 is 3-aminophenyl, B is 1-methoxy-2-propyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0786] R.sup.2 is 3-aminophenyl, B is 2-methoxyethyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0787] R.sup.2 is 3-aminophenyl, B is 2-propyl, A is a bond,
Y.sup.0is 5-amidino-2-thienylmethyl, and X.sup.0 is chloro;
[0788] R.sup.2 is 5-amino-2-methylthiophenyl, B is 2-propyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0789] R.sup.2 is 3-amino-5-carboxyphenyl, B is isopropyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0790] R.sup.2 is 3-amino-5-carbomethoxyphenyl, B is isopropyl, A
is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0791] R.sup.2 is 3-aminophenyl, B is isopropyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is bromo;
[0792] R.sup.2 is 3-amino-5-carboxamidophenyl, B is isopropyl, A is
a bond, Y.sup.0 is 4 amidinobenzyl, and X.sup.0 is chloro;
[0793] R.sup.2 is 3-amino-5-(N-benzyl-N-methylamidocarbonyl)phenyl,
B is isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and
X.sup.0 is chloro;
[0794] R.sup.2 is 3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,
B is isopropyl, A is a bond, Y.sup.0is 4-amidinobenzyl, and X.sup.0
is chloro;
[0795] R.sup.2 is
3-amino-5-(N-(2-phenyl-2-propyl)amidocarbonyl)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro;
[0796] R.sup.2 is
3-amino-5-(N-(2,4-dichlorobenzyl)amidocarbonyl)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro;
[0797] R.sup.2 is 3-amino-5-(N-(4bromobenzyl)amidocarbonyl)phenyl,
B is isopropyl, A is a bond, Y.sup.0is 4-amidinobenzyl, and X.sup.0
is chloro;
[0798] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro;
[0799] R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is isopropyl,
A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0800] R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phen- yl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro;
[0801] R.sup.2 is
3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl, B is isopropyl,
A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0802] R.sup.2 is
3-amino-5-(N-(3-trifluoromethylbenzyl)amidocarbonyl)phen- yl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro;
[0803] R.sup.2 is 3-amino-5-(N-isobutylamidocarbonyl)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro;
[0804] R.sup.2 is 3-amino-5-(N-cyclobutylamidocarbonyl)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro;
[0805] R.sup.2 is 3-amino-5-(N-cyclopentylamidocarbonyl)phenyl, B
is isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0
is chloro;
[0806] R.sup.2 is 3-amino-5-(N-cycloheptylamidocarbonyl)phenyl, B
is isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0
is chloro;
[0807] R.sup.2 is
3-amino-5-(N-(2-pyridylmethyl)amidocarbonyl)phenyl, B is isopropyl,
A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0808] R.sup.2 is
3-amino-5-(N-(3-pyridylmethyl)amidocarbonyl)phenyl, B is isopropyl,
A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0809] R.sup.2 is
3-amino-5-(N-(2-(4-methoxyphenyl)ethyl)amidocarbonyl)phe- nyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro;
[0810] R.sup.2 is
3-amino-5-(N-(3-phenylpropyl)amidocarbonyl)phenyl, B is isopropyl,
A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0811] R.sup.2 is
3-amino-5-(N-(2,2-diphenylethyl)amidocarbonyl)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro;
[0812] R.sup.2 is
3-amino-5-(N-(2-naphthylmethyl)amidocarbonyl)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro;
[0813] R.sup.2 is
3-amino-5-(N-(1,2,3,4tetrahydronaphth-2-ylmethyl)amidoca-
rbonyl)phenyl, B is isopropyl, A is a bond, Y.sup.0is
4-amidinobenzyl, and X.sup.0 is chloro;
[0814] R.sup.2 is 3-aminophenyl, B is 2-propyl, A is a bond,
Y.sup.0 is 4-amidino-3-fluorobenzyl, and X.sup.0 is hydrido;
[0815] R.sup.2 is 3-carboxyphenyl, B is 2-propyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is hydrido;
[0816] R.sup.2 is 3-aminophenyl, B is 2-propyl, A is a bond,
Y.sup.0 is 4-amidino-3-fluorobenzyl, and X.sup.0 is chloro;
[0817] R.sup.2 is 3,5-diaminophenyl, B is 2,2,2-trifluoroethyl, A
is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0818] R.sup.2 is 3,5-diaminophenyl, B is (S)-2-butyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0819] R.sup.2 is 3,5-diaminophenyl, B is isopropyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0820] R.sup.2 is 3,5-diaminophenyl, B is isopropyl, A is a bond,
Y.sup.0is 4-amidino-2-fluorobenzylbenzyl, and X.sup.0 is
chloro;
[0821] R.sup.2 is 3,5-diaminophenyl, B is ethyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0822] R.sup.2 is 3,5-diaminophenyl, B is ethyl, A is a bond,
Y.sup.0 is 4-amidino-2-fluorobenzyl, and X.sup.0 is chloro;
[0823] R.sup.2 is 3-amino-5-carboxyphenyl, B is
2,2,2-trifluoroethyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and
X.sup.0 is chloro;
[0824] R.sup.2 is 3-amino-5-carboxyphenyl, B is (S)-2-butyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is chloro;
[0825] R.sup.2 is 3-amino-5-carboxyphenyl, B is isopropyl, A is a
bond, Y.sup.0 is 4-amidino-2-fluorobenzylbenzyl, and X.sup.0 is
chloro;
[0826] R.sup.2 is 3-amino-5-carboxyphenyl, B is ethyl, A is a bond,
Y.sup.0is 4-amidinobenzyl, and X.sup.0 is chloro;
[0827] R.sup.2 is 3-amino-5-carboxyphenyl, B is ethyl, A is a bond,
Y.sup.0 is 4-amidino-2-fluorobenzyl, and X.sup.0 is chloro;
[0828] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
2,2,2-trifluoroethyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and
X.sup.0 is chloro;
[0829] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
(S)-2-butyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0
is chloro;
[0830] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
isopropyl, A is a bond, Y.sup.0 is 4-amidino-2-fluorobenzylbenzyl,
and X.sup.0 is chloro;
[0831] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
ethyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.0 is
chloro;
[0832] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
ethyl, A is a bond, Y.sup.0 is 4-amidino-2-fluorobenzyl, and
X.sup.0 is chloro;
[0833] R.sup.2 is 3,5-diaminophenyl, B is isopropyl, A is a bond,
Y.sup.0 is 4-amidinobenzylbenzyl, and X.sup.0 is hydrido;
[0834] R.sup.2 is 3-aminophenyl, B is cyclopropyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.O is chloro;
[0835] R.sup.2 is 3-aminophenyl, B is cyclobutyl, A is a bond,
Y.sup.0 is 4-amidino-2-fluorobenzyl, and X.sup.O is chloro;
[0836] R.sup.2 is 3-aminophenyl, B is cyclobutyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.O is chloro;
[0837] R.sup.2 is 3-aminophenyl, B is cyclopropyl, A is a bond,
Y.sup.0 is 4-amidino-2-fluorobenzyl, and X.sup.O is chloro;
[0838] R.sup.2 is 3-aminophenyl, B is cyclobutyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.O is hydrido;
[0839] R.sup.2 is 3-aminophenyl, B is cyclobutyl, A is a bond,
Y.sup.0 is 4-amidino-3-fluorobenzyl, and X.sup.O is chloro;
[0840] R.sup.2 is 3-aminophenyl, B is cyclopentyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.O is chloro;
[0841] R.sup.2 is 5-amino-2-thienyl, B is cyclobutyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.O is chloro;
[0842] R.sup.2 is 3-aminophenyl, B is cyclopropyl, A is CH.sub.2,
Y.sup.0 is 4-amidinobenzyl, and X.sup.O is chloro;
[0843] R.sup.2 is 3-aminophenyl, B is 2-(2R)-bicyclo[2.2.1]-heptyl,
A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O is chloro;
[0844] R.sup.2 is 3-aminophenyl, B is cyclopentyl, A is a bond,
Y.sup.0 is 4-amidino-2-fluorobenzyl, and X.sup.O is chloro;
[0845] R.sup.2 is 3-aminophenyl, B is cyclohexyl, A is
CH.sub.2CH.sub.2,Y.sup.0 is 4-amidinobenzyl, and X.sup.O is
hydrido;
[0846] R.sup.2 is 3-aminophenyl, B is oxalan-2-yl, A is CH.sub.2,
Y.sup.0 is 4-amidinobenzyl, and X.sup.O is chloro;
[0847] R.sup.2 is 3-aminophenyl, B is 1-piperidinyl, A is
CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl, and X.sup.O is
chloro;
[0848] R.sup.2 is 3-aminophenyl, B is 1-pyrrolidinyl, A is
CH.sub.2CH.sub.2CH.sub.2, Y.sup.0 is 4-amidinobenzyl, and X.sup.O
is chloro;
[0849] R.sup.2 is 3-amino-5-carbomethoxyphenyl, B is cyclobutyl, A
is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O is hydrido;
[0850] R.sup.2 is 3-amino-5-carboxyphenyl, B is cyclobutyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O is hydrido;
[0851] R.sup.2 is 3,5-diaminophenyl, B is cyclobutyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.O is hydrido;
[0852] R.sup.2 is 2-amino-6-carboxypyridyl, B is cyclobutyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O is hydrido;
[0853] R.sup.2 is 3-amino-5-carbomethoxyphenyl, B is cyclobutyl, A
is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O is chloro;
[0854] R.sup.2 is 3-amino-5carboxyphenyl, B is cyclobutyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O is chloro;
[0855] R.sup.2 is 3,5-diaminophenyl, B is cyclopropyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.O is chloro;
[0856] R.sup.2 is 3,5-diaminophenyl, B is cyclobutyl, A is a bond,
Y.sup.0 is 4-amidino-2-fluorobenzyl, and X.sup.O is chloro;
[0857] R.sup.2 is 3,5-diaminophenyl, B is cyclopropyl, A is a bond,
Y.sup.0 is 4-amidino-2-fluorobenzyl, and X.sup.O is chloro;
[0858] R.sup.2 is 3,5-diaminophenyl, B is cyclobutyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.O is hydrido;
[0859] R.sup.2 is 3,5-diaminophenyl, B is cyclobutyl, A is a bond,
Y.sup.0 is 4-amidino-3-fluorobenzyl, and X.sup.O is chloro;
[0860] R.sup.2 is 3,5-diaminophenyl, B is cyclopentyl, A is a bond,
Y.sup.0 is 4-amidinobenzyl, and X.sup.O is chloro;
[0861] R.sup.2 is 3-carboxy-5-aminophenyl, B is cyclopropyl, A is a
bond, Y.sup.0is 4-amidinobenzyl, and X.sup.O is chloro;
[0862] R.sup.2 is 3-carboxy-aminophenyl, B is cyclobutyl, A is a
bond, Y.sup.0 is 4-amidino-2-fluorobenzyl, and X.sup.O is
chloro;
[0863] R.sup.2 is 3-carboxy-5-aminophenyl, B is cyclopropyl, A is a
bond, Y.sup.0 is 4-amidino-2-fluorobenzyl, and X.sup.O is
chloro;
[0864] R.sup.2 is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O is hydrido;
[0865] R.sup.2 is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is a
bond, Y.sup.0 is 4-amidino-3-fluorobenzyl, and X.sup.O is
chloro;
[0866] R.sup.2 is 3-carboxy-5-aminophenyl, B is cyclopentyl, A is a
bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O is chloro;
[0867] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
cyclopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O
is chloro;
[0868] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
cyclobutyl, A is a bond, Y.sup.0 is 4-amidino-2-fluorobenzyl, and
X.sup.O is chloro;
[0869] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
cyclobutyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O is
chloro;
[0870] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
cyclopropyl, A is a bond, Y.sup.0 is 4-amidino-2-fluorobenzyl, and
X.sup.O is chloro;
[0871] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
cyclobutyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O is
hydrido;
[0872] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
cyclobutyl, A is a bond, Y.sup.0 is 4-amidino-3-fluorobenzyl, and
X.sup.O is chloro;
[0873] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
cyclopentyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O
is chloro;
[0874] R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is
cyclopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O
is chloro;
[0875] R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclobutyl,
A is a bond, Y.sup.0is 4-amidino-2-fluorobenzyl, and X.sup.O is
chloro;
[0876] R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclobutyl,
A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O is chloro;
[0877] R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is
cyclopropyl, A is a bond, Y.sup.0 is 4-amidino-2-fluorobenzyl, and
X.sup.O is chloro;
[0878] R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclobutyl,
A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O is
hydrido;
[0879] R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclobutyl,
A is a bond, Y.sup.0 is 4-amidino-3-fluorobenzyl, and X.sup.O is
chloro;
[0880] R.sup.2 is
3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is
cyclopentyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O
is chloro;
[0881] R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phe- nyl, B is
cyclopropyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O
is chloro;
[0882] R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phe- nyl, B is
cyclobutyl, A is a bond, Y.sup.0is 4-amidino-2-fluorobenzyl, and
X.sup.O is chloro;
[0883] R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phe- nyl, B is
cyclobutyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O is
chloro;
[0884] R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phe- nyl, B is
cyclopropyl, A is a bond, Y.sup.0 is 4-amidino-2-fluorobenzyl, and
X.sup.O is chloro;
[0885] R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phe- nyl, B is
cyclobutyl, A is a bond, Y.sup.0 is 4-amidinobenzyl, and X.sup.O is
hydrido;
[0886] R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phe- nyl, B is
cyclobutyl, A is a bond, Y.sup.0 is 4-amidino-3-fluorobenzyl, and
X.sup.O is chloro; and
[0887] R.sup.2 is
3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phe- nyl, B is
cyclopentyl, A is a bond, Y.sup.0is 4-amidinobenzyl, and X.sup.O is
chloro.
[0888] Using the examples and methods described herein previously,
the following further additional examples having a guanidinoalkyl
type Y.sup.AT group could be prepared of the formula: 75
[0889] wherein B, A, R.sup.2, X.sup.O, and Y.sup.AT are selected to
form the following compounds:
[0890] R.sup.2 is 3-aminophenyl, B is phenyl, A is
CH.sub.2CH.sub.2,Y.sup.- AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.O is
chloro;
[0891] R.sup.2 is 3,5-diaminophenyl, B is phenyl, A is
CH.sub.2CH.sub.2, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.O is
chloro;
[0892] R.sup.2 is 3-carboxy-5-aminophenyl, B is phenyl, A is
CH.sub.2CH.sub.2, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.O is
chloro;
[0893] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
phenyl, A is CH.sub.2CH.sub.2, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pent- yl, and X.sup.O is
chloro;
[0894] R.sup.2 is 3,5-diaminophenyl, B is isopropyl, A is single
bond, Y.sup.AT is 5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and
X.sup.O is chloro;
[0895] R.sup.2 is 3-carboxy-5-aminophenyl, B is isopropyl, A is
single bond, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.O is
chloro;
[0896] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
isopropyl, A is single bond, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.O is
chloro;
[0897] R.sup.2 is 3,5-diaminophenyl, B is cyclobutyl, A is single
bond, Y.sup.AT is 5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and
X.sup.O is chloro;
[0898] R.sup.2 is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is
single bond, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.O is
chloro;
[0899] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
cyclobutyl, A is single bond, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazoly- l)-2-pentyl, and X.sup.O is
chloro;
[0900] R.sup.2 is 3-aminophenyl, B is phenyl, A is
CH.sub.2CH.sub.2, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.O is
hydrido;
[0901] R.sup.2 is 3,5-diaminophenyl, B is phenyl, A is
CH.sub.2CH.sub.2, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.O is
hydrido;
[0902] R.sup.2 is 3-carboxy-5-aminophenyl, B is phenyl, A is
CH.sub.2CH.sub.2, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.O is
hydrido;
[0903] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
phenyl, A is CH.sub.2CH.sub.2, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pent- yl, and X.sup.O is
hydrido;
[0904] R.sup.2 is 3,5-diaminophenyl, B is isopropyl, A is single
bond, Y.sup.AT is 5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and
X.sup.O is hydrido;
[0905] R.sup.2 is 3-carboxy-5-aminophenyl, B is isopropyl, A is
single bond, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.O is
hydrido;
[0906] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
isopropyl, A is single bond, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.O is
hydrido;
[0907] R.sup.2 is 3,5-diaminophenyl, B is cyclobutyl, A is single
bond, Y.sup.AT is 5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and
X.sup.O is hydrido;
[0908] R.sup.2 is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is
single bond, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and X.sup.O is hydrido;
and
[0909] R.sup.2 is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is
cyclobutyl, A is single bond, Y.sup.AT is
5-guanidino-1-oxo-1-(2-thiazoly- l)-2-pentyl, and X.sup.O is
hydrido.
[0910] Formula (1) compounds of this invention possessing hydroxyl,
thiol, and amine functional groups can be converted to a wide
variety derivatives. A hydroxyl group in the form of an alcohol or
phenol can be readily converted to esters of carboxylic, sulfonic,
carbamic, phosphonic, and phosphoric acids. Acylation to form a
carboxylic acid ester is readily effected using a suitable
acylating reagent such as an aliphatic acid anhydride or acid
chloride. The corresponding aryl and heteroaryl acid anhydrides and
acid chlorides can also be used. Such reactions are generally
carried out using an amine catalyst such as pyridine in an inert
solvent. Similarly, carbamic acid esters (urethanes) can be
obtained by reacting a hydroxyl group with isocyanates and
carbamoyl chlorides. Sulfonate, phosphonate, and phosphate esters
can be prepared using the corresponding acid chloride and similar
reagents. Compounds of Formula (I) that have at least one thiol
group present can be converted to the corresponding thioesters
derivatives analogous to those of alcohols and phenols using the
same reagents and comparable reaction conditions. Compounds of
Formula (I) that have at least one primary or secondary amine group
present can be converted to the corresponding amide derivatives.
Amides of carboxylic acids can be prepared using the appropriate
acid chloride or anhydrides with reaction conditions analogous to
those used with alcohols and phenols. Ureas of the corresponding
primary or secondary amine can be prepared using isocyanates
directly and carbamoyl chlorides in the presence of an acid
scavenger such as triethylamine or pyridine. Sulfonamides can be
prepared from the corresponding sulfonyl chloride in the presence
of aqueous sodium hydroxide. Suitable procedures and methods for
preparing these derivatives can be found in House's Modern
Synthetic Reactions, W. A. Benjamin, Inc., Shriner, Fuson, and
Curtin in The Systematic Identification of Organic Compounds, 5th
Edition, John Wiley & Sons, and Fieser and Fieser in Reagents
for Organic Synthesis, Volume 1, John Wiley & Sons. Reagents of
a wide variety that can be used to derivatize hydroxyl, thiol, and
amines of compounds of Formula (I) are available from commercial
sources or the references cited above, which are incorporated
herein by reference.
[0911] Formula (I) compounds of this invention possessing hydroxyl,
thiol, and amine functional groups can be alkylated to a wide
variety derivatives. A hydroxyl group of compounds of Formula (I)
can be readily converted to ethers. Alkylation to form an ether is
readily effected using a suitable alkylating reagent such as an
alkyl bromide, alkyl iodide or alkyl sulfonate. The corresponding
aralkyl, heteroaralkyl, alkoxyalkyl, aralkyloxyalkyl, and
heteroaralkyloxyalkyl bromides, iodides, and sulfonates can also be
used. Such reactions are generally carried out using an alkoxide
forming reagent such as sodium hydride, potassium t-butoxide,
sodium amide, lithium amide, and n-butyl lithium using an inert
polar solvent such as DMF, DMSO, THF, and similar, comparable
solvents, amine catalyst such as pyridine in an inert solvent.
Compounds of Formula (I) that have at least one thiol group present
can be converted to the corresponding thioether derivatives
analogous to those of alcohols and phenols using the same reagents
and comparable reaction conditions. Compounds of Formula (I) that
have at least one primary, secondary or tertiary amine group
present can be converted to the corresponding quaternary ammonium
derivatives. Quaternary ammonium derivatives can be prepared using
the appropriate bromides, iodides, and sulfonates analogous to
those used with alcohols and phenols. Conditions involve reaction
of the amine by warming it with the alkylating reagent with a
stoichiometric amount of the amine (i.e., one equivalent with a
tertiary amine, two with a secondary, and three with a primary).
With primary and secondary amines, two and one equivalents,
respectively, of an acid scavenger are used concurrently. Tertiary
amines can be prepared from the corresponding primary or secondary
amine by reductive alkylation with aldehydes and ketones using
reduction methods. Suitable procedures and methods for preparing
these derivatives can be found in House's Modern Synthetic
Reactions, W. A. Benjamin, Inc., Shriner, Fuson, and Curtin in The
Systematic Identification of Organic Compounds, 5th Edition, John
Wiley & Sons, and Fieser and Fieser in Reagents for Organic
Synthesis, Volume 1, John Wiley & Sons. Perfluoroalkyl
derivatives can be prepared as described by DesMarteau in J. Chem.
Soc. Chem. Commun. 2241 (1998). Reagents of a wide variety that can
be used to derivative hydroxyl, thiol, and amines of compounds of
Formula (I) are available from commercial sources or the references
cited above, which are incorporated herein by reference.
[0912] The biological activity of the compounds of Examples 1 and 2
and Schemes 1, 2, 3, 4, 5, and 6 can be evaluated using bioassay
procedures below.
Assays for Biological Activity
TF-VIIa Assay
[0913] In this assay 100 nM recombinant soluble tissue factor and 2
nM recombinant human factor VIIa are added to a 96-well assay plate
containing 0.4 mM of the substrate,
N-Methylsulfonyl-D-phe-gly-arg-p-nitr- oaniline and either
inhibitor or buffer (5 mM CaCl.sub.2,50 mM Tris-HCl, pH 8.0, 100 mM
NaCl, 0.1% BSA). The reaction, in a final volume of 100 ul is
measured immediately at 405 nm to determine background absorbance.
The plate is incubated at room temperature for 60 min, at which
time the rate of hydrolysis of the substrate is measured by
monitoring the reaction at 405 nm for the release of
p-nitroaniline. Percent inhibition of TF-VIIa activity is
calculated from OD.sub.405nm value from the experimental and
control sample.
Xa Assay
[0914] 0.3 nM human factor Xa and 0.15 mM
N-.alpha.-Benzyloxycarbonyl-D-ar-
ginyl-L-glycyl-L-arginine-p-nitroaniline-dihydrochloride (S-2765)
are added to a 96-well assay plate containing either inhibitor or
buffer (50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). The
reaction, in a final volume of 100 ul is measured immediately at
405 nm to determine background absorbance. The plate is incubated
at room temperature for 60 min, at which time the rate of
hydrolysis of the substrate is measured by monitoring the reaction
at 405 nm for the release of p-nitroaniline. Percent inhibition of
Xa activity is calculated from OD.sub.405nm value from the
experimental and control sample.
Thrombin Assay
[0915] 0.28 nM human thrombin and 0.06 mM
H-D-Phenylalanyl-L-pipecolyl-L-a- rginine-p-nitroaniline
dihydrochloride are added to a 96-well assay plate containing
either inhibitor or buffer (50 mM Tris-HCl, pH 8.0, 100 mM NaCl,
0.1% BSA). The reaction, in a final volume of 100 ul is measured
immediately at 405 nm to determine background absorbance. The plate
is incubated at room temperature for 60 min, at which time the rate
of hydrolysis of the substrate is measured by monitoring the
reaction at 405 nm for the release of p-nitroaniline. Percent
inhibition of thrombin activity is calculated from OD.sub.405nm
value from the experimental and control sample.
Trypsin Assay
[0916] 5 ug/ml trypsin, type IX from porcine pancreas and 0.375 mM
N-.alpha.-Benzoyl-L-arginine-p-nitroanilide (L-BAPNA) are added to
a 96-well assay plate containing either inhibitor or buffer (50 mM
Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). The reactions, in a final
volume of 100 ul are measured immediately at 405 nm to determine
background absorbance. The plate is incubated at room temperature
for 60 min, at which time the rate of hydrolysis of the substrate
is measured by monitoring the reaction at 405 nm for the release of
p-nitroaniline. Percent inhibition of trypsin activity is
calculated from OD.sub.405nm value from the experimental and
control sample.
[0917] Recombinant soluble TF, consisting of amino acids 1-219 of
the mature protein sequence was expressed in E. coli and purified
using a Mono Q Sepharose FPLC. Recombinant human VIIa was purchased
from American Diagnostica, Greenwich Conn. and chromogenic
substrate N-Methylsulfonyl-D-phe-gly-arg-p-nitroaniline was
prepared by American Peptide Company, Inc., Sunnyvale, Calif.
Factor Xa was obtained from Enzyme Research Laboratories, South
Bend Ind., thrombin from Calbiochem, La Jolla, Calif., and trypsin
and L-BAPNA from Sigma, St. Louis Mo. The chromogenic substrates
S-2765 and S-2238 were purchased from Chromogenix, Sweden.
[0918] The biological activity of the products of Examples 1 and 2
are summarized below in Table 1.
1TABLE 1 Inhibitory Activity of Substituted Quinones toward Factor
Xa, TF-VIIA, Thrombin II, and Trypsin II. Example TF-VIIA Factor Xa
Thrombin II Trpysin II Number IC50 (uM) IC50 (uM) IC50 (uM) IC50
(uM) 1 2.8 >30 >30 0.11 2 1.3 13% 0.96 0.74
* * * * *