U.S. patent application number 10/641611 was filed with the patent office on 2004-02-26 for imidazo-heterobicycles as factor xa inhibitors.
Invention is credited to Clark, Charles G., Han, Qi, Lam, Patrick Y., Richardson, Thomas E..
Application Number | 20040038980 10/641611 |
Document ID | / |
Family ID | 27381362 |
Filed Date | 2004-02-26 |
United States Patent
Application |
20040038980 |
Kind Code |
A1 |
Lam, Patrick Y. ; et
al. |
February 26, 2004 |
Imidazo-heterobicycles as factor xa inhibitors
Abstract
The present application describes imidazo-heterobicycles of
formulas I and III: 1 or pharmaceutically acceptable salt or
prodrug forms thereof. Compounds of the present invention are
useful as inhibitors of trypsin-like serine proteases, specifically
factor Xa.
Inventors: |
Lam, Patrick Y.; (US)
; Clark, Charles G.; (US) ; Han, Qi;
(US) ; Richardson, Thomas E.; (US) |
Correspondence
Address: |
STEPHEN B. DAVIS
BRISTOL-MYERS SQUIBB COMPANY
PATENT DEPARTMENT
P O BOX 4000
PRINCETON
NJ
08543-4000
US
|
Family ID: |
27381362 |
Appl. No.: |
10/641611 |
Filed: |
August 15, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10641611 |
Aug 15, 2003 |
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09898279 |
Jul 3, 2001 |
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6673810 |
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09898279 |
Jul 3, 2001 |
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09470326 |
Dec 22, 1999 |
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6413980 |
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60127633 |
Apr 2, 1999 |
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60113628 |
Dec 23, 1998 |
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Current U.S.
Class: |
514/252.04 ;
514/255.05; 514/256; 514/303; 544/238; 544/333; 544/405;
546/118 |
Current CPC
Class: |
C07D 487/04 20130101;
C07D 471/04 20130101 |
Class at
Publication: |
514/252.04 ;
514/255.05; 514/256; 514/303; 544/238; 544/333; 544/405;
546/118 |
International
Class: |
C07D 471/02; A61K
031/506; A61K 031/501; A61K 031/497 |
Claims
What is claimed is:
1. A compound of formula I: 55or a stereoisomer or pharmaceutically
acceptable salt thereof, wherein; G is a group of formula IIa or
IIb: 56ring D, including the two atoms of Ring E to which it is
attached, is a 5-6 membered non-aromatic ring consisting of carbon
atoms, 0-1 double bonds, and from 0-2 N, and D is substituted with
0-2 R, provided that when ring D is unsubstituted, it contains at
least one heteroatom; alternatively, ring D, including the two
atoms of Ring E to which it is attached, is a 5-6 membered aromatic
system consisting of carbon atoms and from 0-2 heteroatoms selected
from the group consisting of N, O, and S, and D is substituted with
0-2 R, provided that when ring D is unsubstituted, it contains at
least one heteroatom; E is selected from phenyl, pyridyl,
pyrimidyl, pyrazinyl, and pyridazinyl, and is substituted with 0-1
R; R is selected from F, Cl, Br, I, OH, OCH.sub.3,
OCH.sub.2CH.sub.3, OCH(CH.sub.3).sub.2, OCH.sub.2CH.sub.2CH.sub.3,
NH.sub.2, NH(C.sub.1-3 alkyl), N(C.sub.1-3 alkyl).sub.2,
C(.dbd.NH)NH.sub.2, CH.sub.2NH.sub.2, CH.sub.2NH(C.sub.1-3 alkyl),
CH.sub.2N(C.sub.1-3 alkyl).sub.2, CH.sub.2CH.sub.2NH.sub.2,
CH.sub.2CH.sub.2NH(C.sub.1-3 alkyl), and
CH.sub.2CH.sub.2N(C.sub.1-3 alkyl).sub.2; alternatively, the
bridging portion of ring D is absent, ring E is selected from
phenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, and ring E
is substituted with R.sup.a and R.sup.b; R.sup.a is selected from
F, Cl, Br, I, OH, OCH.sub.3, OCH.sub.2CH.sub.3,
OCH(CH.sub.3).sub.2, OCH.sub.2CH.sub.2CH.sub.3, CN,
C(.dbd.NR.sup.8)NR.sup.7R.sup.9, NHC(.dbd.NR.sup.8)NR.sup.7R.sup.9,
NR.sup.8CH(.dbd.NR.sup.7), C(O)NR.sup.7R.sup.8,
(CR.sup.8R.sup.9).sub.tNR- .sup.7R.sup.8, SH, SCH.sub.3,
SCH.sub.2CH.sub.3, SCH(CH.sub.3).sub.2, SCH.sub.2CH.sub.2CH.sub.3,
S(O)R.sup.3b, S(O).sub.2R.sup.3a, S(O).sub.2NR.sup.2R.sup.2a, and
OCF.sub.3; R.sup.b is selected from H, F, Cl, Br, I, C.sub.1-4
alkyl, SR.sup.3, CO.sub.2R.sup.3, NO.sub.2,
(CH.sub.2).sub.tOR.sup.3, OCF.sub.3, CF.sub.3, C(O)NR.sup.7R.sup.8,
and (CR.sup.8R.sup.9).sub.tNR.sup.7R.sup.8; alternatively, R.sup.a
and R.sup.b combine to form methylenedioxy or ethylenedioxy; A is
selected from: C.sub.3-10 carbocycle substituted with 0-2 R.sup.4,
and 5-10 membered heterocycle consisting of: carbon atoms and 1-4
heteroatoms selected from the group consisting of N, O, and S
substituted with 0-2 R.sup.4; B is selected from: H, Y, X-Y,
C(.dbd.NR.sup.2)NR.sup.2R.sup.2a, and
NR.sup.2C(.dbd.NR.sup.2)NR.sup.2R.sup.2a, provided that Z and B are
attached to different atoms on A; X is selected from C.sub.1-4
alkylene, --CR.sup.2(CR.sup.2R.sup.2b) (CH.sub.2).sub.t--,
--C(O)--, --C (.dbd.NR.sup.1c)--, --CR.sup.2 (NR.sup.1cR.sup.2)--,
--CR.sup.2 (OR.sup.2)--, --CR.sup.2(SR.sup.2)--,
C(O)CR.sup.2R.sup.2a--, CR.sup.2R.sup.2aC(O), --S--, --S(O)--,
--S(O).sub.2--, --SCR.sup.2R.sup.2a--, --S(O)CR.sup.2R.sup.2a--,
--S(O).sub.2CR.sup.2R.su- p.2a--, --CR.sup.2R.sup.2aS--,
--CR.sup.2R.sup.2aS(O)--, --CR.sup.2R.sup.2aS(O).sub.2--,
--S(O).sub.2NR.sup.2--, --NR.sup.2S(O).sub.2--,
--NR.sup.2S(O).sub.2CR.sup.2R.sup.2a--,
--CR.sup.2R.sup.2aS(O).sub.2NR.sup.2--,
--NR.sup.2S(O).sub.2NR.sup.2--, --C(O)NR.sup.2--, --NR.sup.2C(O)--,
--C(O)NR.sup.2CR.sup.2R.sup.2a--, --NR.sup.2C(O)CR.sup.2R.sup.2a
--, --CR.sup.2R.sup.2aC(O)NR.sup.2--,
--CR.sup.2R.sup.2aNR.sup.2C(O)--, --NR.sup.2C(O)O--,
--OC(O)NR.sup.2--, --NR.sup.2C(O)NR.sup.2--, --NR.sup.2--,
--NR.sup.2CR.sup.2R.sup.2a--, --CR.sup.2R.sup.2aNR.sup.2--, O,
--CR.sup.2R.sup.2aO--, and --OCR.sup.2R.sup.2a--; Y is selected
from: CH.sub.2NR.sup.2R.sup.2a; CH.sub.2CH.sub.2NR.sup.2R.sup.2a;
C.sub.3-10 carbocycle substituted with 0-2 R.sup.4a, and, 5-10
membered heterocycle consisting of: carbon atoms and 1-4
heteroatoms selected from the group consisting of N, O, and S
substituted with 0-2 R.sup.4a; R.sup.1a is selected from H,
--(CH.sub.2).sub.r--R.sup.1b, --CH.dbd.CH--R.sup.1b,
NCH.sub.2R.sup.1c, OCH.sub.2R.sup.1c, SCH.sub.2R.sup.1c,
NH(CH.sub.2).sub.2(CH.sub.2).sub.tR- ib,
O(CH.sub.2).sub.2(CH.sub.2).sub.tR.sup.1b,
S(CH.sub.2).sub.2(CH.sub.2)- .sub.tRib,
S(O).sub.p(CH.sub.2).sub.rR.sup.1d, O(CH.sub.2).sub.rR d, NR.sup.3
(CH.sub.2).sub.rR.sup.1d, OC(O)NR.sup.3(CH.sub.2).sub.rR.sup.1d,
NR.sup.3C(O)NR.sup.3(CH.sub.2)R.sup.1d,
NR.sup.3C(O)O(CH.sub.2).sub.rR.su- p.1d, and NR.sup.3C(O)
(CH.sub.2).sub.rR.sup.1d, provided that R.sup.1a forms other than
an N-halo, N--N, N--S, N--O, or N--CN bond; R.sup.1b is selected
from H, C.sub.1-3 alkyl, F, Cl, Br, I, --CN, --CHO,
(CF.sub.2).sub.rCF.sub.3, (CH.sub.2).sub.rOR.sup.2,
NR.sup.2R.sup.2a, C(O)R.sup.2c, OC(O)R.sup.2,
(CF.sub.2).sub.rCO.sub.2R.sup.2a, S(O).sub.pR.sup.2b,
NR.sup.2(CH.sub.2).sub.rOR.sup.2,
C(.dbd.NR.sup.2c)NR.sup.2R.sup.2a, NR.sup.2C(O)R.sup.2b,
NR.sup.2C(O)NHR.sup.2b, NR.sup.2C(O).sub.2R.sup.2a,
OC(O)NR.sup.2aR.sup.2b, C(O)NR.sup.2R.sup.2a, C(O)NR.sup.2
(CH.sub.2).sub.rOR.sup.2, SO.sub.2NR.sup.2R.sup.2a,
NR.sup.2SO.sub.2R.sup.2b, C.sub.3-6 carbocycle substituted with 0-2
R.sup.4a, and 5-10 membered heterocycle consisting of carbon atoms
and from 1-4 heteroatoms selected from the group consisting of N,
O, and S substituted with 0-2 R.sup.4a, provided that Rib forms
other than an N-halo, N--N, N--S, N--O, or N--CN bond; R.sup.1c is
selected from H, CH(CH.sub.2OR.sup.2).sub.2, C(O)R.sup.2c,
C(O)NR.sup.2R.sup.2a, S(O)R.sup.2b, S(O).sub.2R.sup.2b, and
SO.sub.2NR.sup.2R.sup.2a; R.sup.1d is selected from C.sub.3-6
carbocycle substituted with 0-2 R.sup.4a, and 5-10 membered
heterocycle consisting of carbon atoms and from 1-4 heteroatoms
selected from the group consisting of N, O, and S substituted with
0-2 R.sup.4a, provided that R.sup.1d forms other than an N--N,
N--S, or N--O bond; R.sup.2, at each occurrence, is selected from
H, CF.sub.3, C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocycle
substituted with 0-2 R.sup.4b, a C.sub.3-6
carbocyclic-CH.sub.2-residue substituted with 0-2 R.sup.4b, and 5-6
membered heterocycle consisting of: carbon atoms and 1-4
heteroatoms selected from the group consisting of N, O, and S
substituted with 0-2 R.sup.4b; R.sup.2a, at each occurrence, is
selected from H, CF.sub.3, C.sub.1-6 alkyl, benzyl, C.sub.3-6
carbocycle substituted with 0-2 R.sup.4b, and 5-6 membered
heterocycle consisting of: carbon atoms and 1-4 heteroatoms
selected from the group consisting of N, O, and S substituted with
0-2 R.sup.4b; R.sup.2b, at each occurrence, is selected from
CF.sub.3, C.sub.1-4 alkoxy, C.sub.1-6 alkyl, benzyl, C.sub.3-6
carbocycle substituted with 0-2 R.sup.4b, and 5-6 membered
heterocycle consisting of: carbon atoms and 1-4 heteroatoms
selected from the group consisting of N, O, and S substituted with
0-2 R.sup.4b; R.sup.2c, at each occurrence, is selected from
CF.sub.3, OH, C.sub.1-4 alkoxy, C.sub.1-6 alkyl, benzyl, C.sub.3-6
carbocyclic residue substituted with 0-2 R.sup.4b, and 5-6 membered
heterocyclic system containing from 1-4 heteroatoms selected from
the group consisting of N, O, and S substituted with 0-2 R.sup.4b;
alternatively, R.sup.2 and R.sup.2a, together with the atom to
which they are attached, combine to form a 5 or 6 membered
saturated, partially saturated or unsaturated ring substituted with
0-2 R.sup.4b and consisting of: 0-1 additional heteroatoms selected
from the group consisting of N, O, and S; R.sup.3, at each
occurrence, is selected from H, C.sub.1-4 alkyl, and phenyl;
R.sup.3a, at each occurrence, is selected from H, C.sub.1-4 alkyl,
benzyl, and phenyl; R.sup.3b, at each occurrence, is selected from
H, C.sub.1-4 alkyl, and phenyl; R.sup.3c, at each occurrence, is
selected from C.sub.1-4 alkyl, benzyl, and phenyl; R.sup.3d, at
each occurrence, is selected from H, C.sub.1-4 alkyl, C.sub.1-4
alkyl-phenyl, and C(.dbd.O)R.sup.3c; R.sup.4, at each occurrence,
is selected from H, .dbd.O, (CH.sub.2).sub.rOR.sup.2, F, Cl, Br, I,
C.sub.1-4 alkyl, --CN, NO.sub.2, (CH.sub.2).sub.rNR.sup.2R.sup.2a,
(CH.sub.2).sub.rC(O)R.sup.2c, NR.sup.2C(O)R.sup.2b,
C(O)NR.sup.2R.sup.2a, NR.sup.2C(O)NR.sup.2R.sup.2a,
C(.dbd.NR.sup.2)NR.sup.2R.sup.2a,
C(.dbd.NS(O).sub.2R.sup.5)NR.sup.2R.sup- .2a,
NHC(.dbd.NR.sup.2)NR.sup.2R.sup.2a,
C(O)NHC(.dbd.NR.sup.2)NR.sup.2R.s- up.2a, SO.sub.2NR.sup.2R.sup.2a,
NR.sup.2SO.sub.2NR.sup.2R.sup.2a, NR.sup.2SO.sub.2--C.sub.1-4
alkyl, NR.sup.2SO.sub.2R.sup.5, S(O).sub.pR.sup.5,
(CF.sub.2).sub.rCF.sub.3, NCH.sub.2R.sup.1c, OCH.sub.2R.sup.1c,
SCH.sub.2R.sup.1c, N(CH.sub.2).sub.2(CH.sub.2).sub.tR.- sup.1b,
O(CH.sub.2).sub.2(CH.sub.2).sub.tR.sup.1b, and S(CH.sub.2) 2
(CH.sub.2).sub.tR.sup.1b; alternatively, one R.sup.4 is a 5-6
membered aromatic heterocycle consisting of: carbon atoms and 1-4
heteroatoms selected from the group consisting of N, O, and S;
R.sup.4a, at each occurrence, is selected from H, .dbd.O,
(CH.sub.2).sub.rOR.sup.2, (CH.sub.2).sub.r--F,
(CH.sub.2).sub.r--Br, (CH.sub.2).sub.r--Cl, Cl, Br, F, I, C.sub.1-4
alkyl, s-CN, NO.sub.2, (CH.sub.2).sub.rNR.sup.2R.sup.2a,
(CH.sub.2).sub.rC(O)R.sup.2c, NR.sup.2C(O)R.sup.2b,
C(O)NR.sup.2R.sup.2a, (CH.sub.2).sub.rN.dbd.CHOR.sup.3,
C(O)NH(CH.sub.2).sub.2NR.sup.2R.sup.2a,
NR.sup.2C(O)NR.sup.2R.sup.2a, C(.dbd.NR.sup.2)NR.sup.2R.sup.2a,
NHC(.dbd.NR.sup.2)NR.sup.2R.sup.2a, SO.sub.2NR.sup.2R.sup.2a,
NR.sup.2SO.sub.2NR.sup.2R.sup.2a, NR.sup.2SO.sub.2--C.sub.1-4
alkyl, C(O)NHSO.sub.2--C.sub.1-4 alkyl, NR.sup.2SO.sub.2R.sup.5,
S(O).sub.pR.sup.5, and (CF.sub.2).sub.rCF.sub.3; alternatively, one
R.sup.4a is phenyl substituted with 0-1 R.sup.5 or a 5-6 membered
aromatic heterocycle consisting of: carbon atoms and 1-4
heteroatoms selected from the group consisting of N, O, and S
substituted with 0-1 R.sup.5; R.sup.4b, at each occurrence, is
selected from H, .dbd.O, (CH.sub.2).sub.rOR.sup.3, F, Cl, Br, I,
C.sub.1-4 alkyl, --CN, NO.sub.2, (CH.sub.2).sub.rNR.sup.3R.sup.3a,
(CH.sub.2).sub.rC(O)R.sup.3, (CH.sub.2).sub.rC(O)OR.sup.3c,
NR.sup.3C(O)R.sup.3a, C(O)NR.sup.3R.sup.3a,
NR.sup.3C(O)NR.sup.3R.sup.3a, C(.dbd.NR.sup.3)NR.sup.3R.sup.3a,
NR.sup.3C(.dbd.NR.sup.3)NR.sup.3R.sup.3- a,
SO.sub.2NR.sup.3R.sup.3a, NR.sup.3SO.sub.2NR.sup.3R.sup.3a,
NR.sup.3SO.sub.2--C.sub.1-4 alkyl, NR.sup.3SO.sub.2CF.sub.3,
NR.sup.3SO.sub.2-phenyl, S(O).sub.pCF.sub.3, S(O).sub.p--C.sub.1-4
alkyl, S(O).sub.p-phenyl, and (CF.sub.2).sub.rCF.sub.3; R.sup.5, at
each occurrence, is selected from H, C.sub.1-6 alkyl, .dbd.O,
(CH.sub.2).sub.rOR.sup.3, F, Cl, Br, I, C.sub.1-4 alkyl, --CN,
NO.sub.2, (CH.sub.2).sub.rNR.sup.3R.sup.3a,
(CH.sub.2).sub.rC(O)R.sup.3, (CH.sub.2).sub.rC(O)OR.sup.3c,
NR.sup.3C(O)R.sup.3a, C(O)NR.sup.3R.sup.3a,
NR.sup.3C(O)NR.sup.3R.sup.3a, CH(.dbd.NOR.sup.3d),
C(.dbd.NR.sup.3)NR.sup.3R.sup.3a, NR.sup.3c
(.dbd.NR.sup.3)NR.sup.3R.sup.- 3a, SO.sub.2NR.sup.3R.sup.3a,
NR.sup.3SO.sub.2NR.sup.3R.sup.3a, NR.sup.3SO.sub.2--C.sub.1-4
alkyl, NR.sup.3SO.sub.2CF.sub.3, NR.sup.3SO.sub.2-phenyl,
S(O).sub.pCF.sub.3, S(O).sub.p--C.sub.1-4 alkyl, S(O).sub.p-phenyl,
(CF.sub.2).sub.rCF.sub.3, phenyl substituted with 0-2 R.sup.6,
naphthyl substituted with 0-2 R.sup.6, and benzyl substituted with
0-2 R.sup.6; R.sup.6, at each occurrence, is selected from H, OH,
(CH.sub.2).sub.rOR.sup.2, halo, C.sub.1-4 alkyl, CN, NO.sub.2,
(CH.sub.2).sub.rNR.sup.2R.sup.2a, (CH.sub.2).sub.rC(O)R.sup.2b,
NR.sup.2C(O)R.sup.2b, NR.sup.2C(O)NR.sup.2R.sup.2a, C
(.dbd.NH)NH.sub.2, NHC (.dbd.NH)NH.sub.2, SO.sub.2NR.sup.2R.sup.2a,
NR.sup.2SO.sub.2NR.sup.2- R.sup.2a, and NR.sup.2SO.sub.2C.sub.1-4
alkyl; R.sup.7, at each occurrence, is selected from H, OH,
C.sub.1-6 alkyl, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkoxy,
C.sub.1-4 alkoxycarbonyl, (CH.sub.2).sub.n-phenyl, C.sub.6-10
aryloxy, C.sub.6-10 aryloxycarbonyl, C.sub.6-10 arylmethylcarbonyl,
C.sub.1-4 alkylcarbonyloxy C.sub.1-4 alkoxycarbonyl, C.sub.6-10
arylcarbonyloxy C.sub.1-4 alkoxycarbonyl, C.sub.1-6
alkylaminocarbonyl, phenylaminocarbonyl, and phenyl C.sub.1-4
alkoxycarbonyl; R.sup.8, at each occurrence, is selected from H,
C.sub.1-6 alkyl, and (CH.sub.2) n-phenyl; alternatively, R.sup.7
and R.sup.8 combine to form a 5 or 6 membered saturated, ring which
contains from 0-1 additional heteroatoms selected from the group
consisting of N, O, and S; R.sup.9, at each occurrence, is selected
from H, C.sub.1-6 alkyl, and (CH.sub.2).sub.n-phenyl; n, at each
occurrence, is selected from 0, 1, 2, and 3; p, at each occurrence,
is selected from 0, 1, and 2; r, at each occurrence, is selected
from 0, 1, 2, 3, 4, 5, and 6; s, at each occurrence, is selected
from 0, 1, and 2; and, t, at each occurrence, is selected from 0,
1, 2, and 3.
2. A compound according to claim 1, wherein: G is selected from the
group: 57585960A is selected from one of the following carbocyclic
and heterocyclic systems which are substituted with 0-2 R.sup.4;
phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl,
morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl,
isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl,
oxadiazolyl, thiadiazolyl, triazolyl, 1,2,3-oxadiazolyl,
1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl,
1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,
1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl,
1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl, benzothiofuranyl,
indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, indazolyl,
benzisoxazolyl, benzisothiazolyl, and isoindazolyl; B is Y or X-Y;
X is selected from C.sub.1-4 alkylene, --C(O)--, --C (.dbd.NR)--,
--CR.sup.2 (NR.sup.2R.sup.2a)--, --C(O)CR.sup.2R.sup.2a--,
--CR.sup.2R.sup.2aC(O), --C(O)NR.sup.2--, --NR.sup.2C(O)--,
--C(O)NR.sup.2CR.sup.2R.sup.2a--, --NR.sup.2C(O)CR.sup.2R.sup.2a--,
CR.sup.2R.sup.2aC(O)NR.sup.2, --CR.sup.2R.sup.2aNR.sup.2C(O)--,
--NR.sup.2C(O)NR.sup.2--, --NR.sup.2--, NR.sup.2CR.sup.2R.sup.2a--,
CR.sup.2R.sup.2aNR.sup.2--, O, --CR.sup.2R.sup.2aO--, and
--OCR.sup.2R.sup.2a--; Y is CH.sub.2NR.sup.2R.sup.2a or
CH.sub.2CH.sub.2NR.sup.2R.sup.2a; alternatively, Y is selected from
one of the following carbocyclic and heterocyclic systems that are
substituted with 0-2 R.sup.4a; cyclopropyl, cyclopentyl,
cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl,
furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl,
isoxazolyl, isoxazolinyl, thiazolyl, isothiazolyl, pyrazolyl,
imidazolyl, oxadiazolyl, thiadiazolyl, triazolyl,
1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,
1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,
1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl,
1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl,
benzothiofuranyl, indolyl, benzimidazolyl, benzoxazolyl,
benzthiazolyl, indazolyl, benzisoxazolyl, benzisothiazolyl, and
isoindazolyl; alternatively, Y is selected from the following
bicyclic heteroaryl ring systems: 61K is selected from O, S, NH,
and N.
3. A compound according to claim 2, wherein: G is selected from the
group: 6263
4. A compound according to claim 3, wherein: G is selected from:
64
5. A compound according to claim 4, wherein: A is selected from
phenyl, pyridyl, and pyrimidyl, and is substituted with 0-2
R.sup.4; and, B is selected from phenyl, pyrrolidino,
N-pyrrolidino-carbonyl, morpholino, N-morpholino-carbonyl,
1,2,3-triazolyl, imidazolyl, and benzimidazolyl, and is substituted
with 0-1 R.sup.4a; R.sup.2, at each occurrence, is selected from H,
CH.sub.3, CH.sub.2CH.sub.3, cyclopropylmethyl, cyclobutyl, and
cyclopentyl; R.sup.2a, at each occurrence, is H or CH.sub.3;
alternatively, R.sup.2 and R.sup.2a, together with the atom to
which they are attached, combine to form pyrrolidine substituted
with 0-2 R.sup.4b; R.sup.4, at each occurrence, is selected from
OH, (CH.sub.2).sub.rOR.sup.2, halo, C.sub.1-4 alkyl,
(CH.sub.2).sub.rNR.sup.2- R.sup.2a, and (CF.sub.2).sub.rCF.sub.3;
R.sup.4a is selected from C.sub.1-4 alkyl, CF.sub.3,
(CH.sub.2).sub.rOR.sup.2, (CH.sub.2).sub.rNR.sup.2R.sup.2a,
S(O).sub.pR.sup.5, SO.sub.2NR.sup.2R.sup.2a, and
1-CF.sub.3-tetrazol-2-yl; R.sup.4b, at each occurrence, is selected
from H, CH.sub.3, and OH; R.sup.5, at each occurrence, is selected
from CF.sub.3, C.sub.1-6 alkyl, phenyl, and benzyl; and, r, at each
occurrence, is selected from 0, 1, and 2.
6. A compound according to claim 5, wherein: A is selected from the
group: phenyl, 2-pyridyl, 3-pyridyl, 2-pyrimidyl, 2-Cl-phenyl,
3-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 2-methylphenyl, 2-aminophenyl,
and 2-methoxyphenyl; and, B is selected from the group:
2-(aminosulfonyl)phenyl, 2-(methylaminosulfonyl)phenyl,
1-pyrrolidinocarbonyl, 2-(methylsulfonyl)phenyl,
2-(N,N-dimethylaminometh- yl)phenyl,
2-(N-pyrrolidinylmethyl)phenyl, 1-methyl-2-imidazolyl,
2-methyl-1-imidazolyl, 2-(dimethylaminomethyl)-1-imidazolyl,
2-(N-(cyclopropylmethyl)aminomethyl)phenyl,
2-(N-(cyclobutyl)aminomethyl)- phenyl,
2-(N-(cyclopentyl)aminomethyl)phenyl, and 2-(N-(3-hydroxypyrrolidi-
nyl)methyl)phenyl.
7. A compound according to claim 1, wherein the compound is
selected from:
1-(4-methoxyphenyl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-7-oxo-6,7-dih-
ydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(methylamino)-
methyl]-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(dimethylamino)methyl]-1,1'-biphenyl-4-yl}-7-o-
xo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(N--
ethyl-N-methylamino)methyl]-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imida-
zolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(N-methyl-N-propylamino)me-
thyl]-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-biphenyl-4-yl}-7--
oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[1-pyrrolidinyl]methyl-
}-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4-
,5-c]pyridine;
6-(2'-([(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-
-4-yl)-1-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(4-me-
thoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(4-methoxyp-
henyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(4-methoxyphenyl)-7-oxo-6,7-
-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(4-{2-[(dimethylamino)methyl]-1H-i-
midazol-1-yl}phenyl)-1-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,-
5-c]pyridine;
1-(4-methoxyphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]--
7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl)(me-
thyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-6,7-dihyd-
ro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl)amino]methyl]-1,1'-
-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]p-
yridine;
1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-y-
l}phenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-6,7-dih-
ydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-
-1-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-biphenyl-4-yl}-7-ox-
o-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(met-
hylamino)methyl]-3-fluoro-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazo-
lo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(dimethylamino)methyl]-3-flu-
oro-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-fluoro-1,1'-b-
iphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fluoro-1,1'--
biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1'-biphenyl-
-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxyp-
henyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl]-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl}-1-(4-
-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(4-methoxyphenyl)-
-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(4-{2-[(dimethylamino)me-
thyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-1-(4-methoxyphenyl)-7-oxo-6,7-dih-
ydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-[4-(2-methyl-1H-im-
idazol-1-yl)-2-fluoro-phenyl]-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridin-
e;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4--
yl)-1-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-m-
ethoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-2-flu-
oro-phenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-ox-
o-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-methylsulfonyl-3-fluoro-1-
,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5--
c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl-
}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-
-{2'-[(methylamino)methyl]-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidaz-
olo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(dimethylamino)methyl]--
1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-1,1'-biphen-
yl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'-biphe-
nyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-biphenyl-4-yl-
}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[1-pyrrolidinyl]me-
thyl}-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imi-
dazolo[4,5-c]pyridine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'--
biphenyl-4-yl)-1-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5--
c]pyridine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4--
yl)-1-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3-aminomet-
hylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(3-aminomethylphenyl)-7-oxo-
-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(4-{2-[(dimethylamino)methyl]--
1H-imidazol-1-yl}phenyl)-1-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imid-
azolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-[4-(2-methyl-1H-imidazol-1-
-yl)phenyl]-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-am-
inomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminomethy-
lphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}ph-
enyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-7-oxo-6,7-
-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-methylsulfonyl-1,1'-biphenyl-4-
-yl)-1-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine-
;
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-biphenyl-4-yl}-
-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6--
{2'-[(methylamino)methyl]-3-fluoro-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1-
H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(dimethylamino)-
methyl]-3-fluoro-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]-
pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3--
fluoro-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fluoro-1-
,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1'-biph-
enyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomet-
hylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-[[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl}-1-(3-
-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(3-aminomethylphe-
nyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-1-(3-a-
minomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-phenyl]-
-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl)(m-
ethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-7-
-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl)amin-
o]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-7-oxo-6,7-d-
ihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-(4-{2-[(meth-
ylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-7-oxo-6,7-dihydro-1H-im-
idazolo[4,5-c]pyridine;
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-
-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-
-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'--
yl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo-
[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(methylamino)methyl]-
-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(dimethylamino)methyl]-1,1'-biphenyl-
-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-1,1'--
biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'-
-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-bipheny-
l-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-
-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-am-
inobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-am-
inobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-[(2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3-aminobe-
nzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(3-aminobenzisoxazol-5'-yl)-
-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(4-{2-[(dimethylamino)me-
thyl]-1H-imidazol-1-yl}phenyl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dih-
ydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(2-me-
thyl-1H-imidazol-1-yl)phenyl]-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridin-
e;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3--
aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminobenzi-
soxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-
-yl}phenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-o-
xo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-methylsulfonyl-1,1'-biph-
enyl-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,-
5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[aminomethyl]-3-fluoro-1-
,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-b-
iphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-
-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-flu-
oro-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fl-
uoro-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1-
'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminoben-
zisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyrid-
ine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl--
4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]p-
yridine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4--
yl}-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyr-
idine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(3-aminoben-
zisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-1-(3-a-
minobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-p-
henyl]-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyrid-
ine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1--
(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-
-yl}-2-fluoro-phenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5-
'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol--
5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
3-[6,7-dihydro-6-[2'-[aminomethyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazol-
o[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[methylamino]methyl]-
[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[dimethylamino]methyl][1,1'-biphenyl]-4-yl]-7-oxo-1-
H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[4-hydroxy-
piperidin-1-yl]methyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyrid-
in-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[N-ethyl-N-methylamino]methyl][1,-
1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[pyrrolidin-1-yl]methyl][1,1'-biphenyl]-4-yl]-7-oxo-
-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[3(R)-hy-
droxypyrrolidin-1-yl]methyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c-
]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[3(S)-hydroxypyrrolidin-1-y-
l]methyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benza-
mide;
3-[6,7-dihydro-6-[2'-[[N-propyl-N-methylamino]methyl][1,1'-biphenyl]-
-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[t-butylamino]methyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-
-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-{4-[3-(aminosulf-
onyl)-4-pyridinyl]phenyl}-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}phenyl)-7-
-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-[4-(2-met-
hyl-1H-imidazol-1-yl)phenyl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzami-
de;
3-[6,7-dihydro-6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biph-
enyl-4-yl) 7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)--
7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-(4-{2-[(-
methylamino)methyl]-1H-imidazol-1-yl}phenyl)-7-oxo-1H-imidazolo[4,5-c]pyri-
din-1-yl]benzamide;
3-[6,7-dihydro-6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-
-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-(2'-met-
hylsulfonyl-1,1'-biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benz-
amide;
3-[6,7-dihydro-6-[2'-[aminomethyl]-3-fluoro-[1,1'-biphenyl]-4-yl]-7-
-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[met-
hylamino]methyl]-3-fluoro-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]p-
yridin-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[dimethylamino]methyl]-3-fluo-
ro-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[4-hydroxypiperidin-1-yl]methyl]-3-fluoro-[1,1'-bip-
henyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[N-ethyl-N-methylamino]methyl]-3-fluoro-[1,1'-biphe-
nyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[pyrrolidin-1-yl]methyl]-3-fluoro[1,1'-biphenyl]-4--
yl]-7-oxo-1H-imidazolo[4,5-c]pyridin 1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[3(R)-hydroxypyrrolidin-1-yl]methyl]-3-fluoro-[1,1'-
-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[3(S)-hydroxypyrrolidin-1-yl]methyl]-3-fluoro-[1,1'-
-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[N-propyl-N-methylamino]methyl]-3-fluoro-[1,1'-biph-
enyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-[2'-[[t-butylamino]methyl]-3-fluoro-[1,1'-biphenyl]-4-yl-
]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-{4-[3--
(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-7-oxo-1H-imidazolo[4,5-c]pyr-
idin-1-yl]benzamide;
3-[6,7-dihydro-6-(4-{2-[(dimethylamino)methyl]-1H-imi-
dazol-1-yl}-2-fluoro-phenyl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzami-
de;
3-[6,7-dihydro-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-phenyl]-7-oxo-
-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-(2'-{[(2-hydr-
oxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-7-oxo-1H-imida-
zolo[4,5-c]pyridin-lyl]benzamide;
3-[6,7-dihydro-6-(2'-{[(2-hydroxyethyl)a-
mino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-
-1-yl]benzamide;
3-[6,7-dihydro-6-(4-{2-[(methylamino)methyl]-1H-imidazol--
1-yl}-2-fluoro-phenyl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[6,7-dihydro-6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-7-oxo-1H--
imidazolo[4,5-c]pyridin-1-yl]benzamide; and,
3-[6,7-dihydro-6-(2'-methylsu-
lfonyl-3-fluoro-1,1'-biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]-
benzamide; or a pharmaceutically acceptable salt form thereof.
8. A compound of formula III: 65or a stereoisomer or
pharmaceutically acceptable salt thereof, wherein; ring M,
including M.sub.1 and M.sub.2, is a 6 or 7 membered carbocycle or 6
or 7 membered heterocycle, consisting of: carbon atoms, and 1-3
heteroatoms selected from O, S(O).sub.p, N, and N-Z.sup.2; provided
that ring M is other than: 66ring M is substituted with 0-2 R.sup.3
and 0-2 carbonyl groups, and, comprises: 0-2 double bonds;
alternatively, M.sub.1 is C(O), M.sub.2 is N, and the remainder of
ring M is S(O).sub.2; M.sub.3 is -A-B; G is a group of formula IIa
or IIb: 67ring D, including the two atoms of Ring E to which it is
attached, is a 5-6 membered non-aromatic ring consisting of carbon
atoms, 0-1 double bonds, and from 0-2 N, and D is substituted with
0-2 R, provided that when ring D is unsubstituted, it contains at
least one heteroatom; alternatively, ring D, including the two
atoms of Ring E to which it is attached, is a 5-6 membered aromatic
system consisting of carbon atoms and from 0-2 heteroatoms selected
from the group consisting of N, O, and S, and D is substituted with
0-2 R, provided that when ring D is unsubstituted, it contains at
least one heteroatom; E is selected from phenyl, pyridyl,
pyrimidyl, pyrazinyl, and pyridazinyl, and is substituted with 0-1
R; R is selected from F, Cl, Br, I, OH, OCH.sub.3,
OCH.sub.2CH.sub.3, OCH(CH.sub.3).sub.2, OCH.sub.2CH.sub.2CH.sub.3,
NH.sub.2, NH(C.sub.1-3 alkyl), N(C.sub.1-3 alkyl).sub.2,
C(.dbd.NH)NH.sub.2, CH.sub.2NH.sub.2, CH.sub.2NH(C.sub.1-3 alkyl),
CH.sub.2N(C.sub.1-3 alkyl).sub.2, CH.sub.2CH.sub.2NH.sub.2,
CH.sub.2CH.sub.2NH(C.sub.1-3 alkyl), and
CH.sub.2CH.sub.2N(C.sub.1-3 alkyl).sub.2; alternatively, the
bridging portion of ring D is absent, ring E is selected from
phenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, and ring E
is substituted with R.sup.a and R.sup.b; R.sup.a is selected from
F, Cl, Br, I, OH, OCH.sub.3, OCH.sub.2CH.sub.3,
OCH(CH.sub.3).sub.2, OCH.sub.2CH.sub.2CH.sub.3, CN,
C(.dbd.NR.sup.8)NR.sup.7R.sup.9, NHC(.dbd.NR.sup.8)NR.sup.7R.sup.9,
NR.sup.8CH(.dbd.NR.sup.7), C(O)NR.sup.7R.sup.8,
(CR.sup.8R.sup.9).sub.tNR- .sup.7R.sup.8, SH, SCH.sub.3,
SCH.sub.2CH.sub.3, SCH(CH.sub.3).sub.2, SCH.sub.2CH.sub.2CH.sub.3,
S(O)R.sup.3b, S(O).sub.2R.sup.3a, S(O).sub.2NR.sup.2R.sup.2a, and
OCF.sub.3; R.sup.b is selected from H, F, Cl, Br, I, C.sub.1-4
alkyl, SR.sup.3, CO.sub.2R.sup.3, NO.sub.2,
(CH.sub.2).sub.tOR.sup.3, OCF.sub.3, CF.sub.3, C(O)NR.sup.7R.sup.8,
and (CR.sup.8R.sup.9).sub.tNR.sup.7R.sup.8; alternatively, R.sup.a
and R.sup.b combine to form methylenedioxy or ethylenedioxy; A is
selected from: C.sub.3-10 carbocycle substituted with 0-2 R.sup.4,
and 5-10 membered heterocycle consisting of: carbon atoms and 1-4
heteroatoms selected from the group consisting of N, O, and S
substituted with 0-2 R.sup.4; B is selected from: H, Y, X-Y,
C(.dbd.NR.sup.2)NR.sup.2R.sup.2a, and
NR.sup.2C(.dbd.NR.sup.2)NR.sup.2R.sup.2a, provided that Z and B are
attached to different atoms on A; X is selected from C.sub.1-4
alkylene, --CR.sup.2(CR.sup.2R.sup.2b) (CH.sub.2).sub.t--,
--C(O)--, --C(.dbd.NR.sup.1c)--, --CR.sup.2(NR.sup.1cR.sup.2)--,
--CR.sup.2(OR.sup.2)--, --CR.sup.2(SR.sup.2)--,
C(O)CR.sup.2R.sup.2a--, CR.sup.2R.sup.2aC(O), --S--, --S(O)--,
--S(O).sub.2--, --SCR.sup.2R.sup.2a--, --S(O)CR.sup.2R.sup.2a--,
--S(O).sub.2CR.sup.2R.su- p.2a--, --CR.sup.2R.sup.2aS-,
--CR.sup.2R.sup.2aS(O)--, --CR.sup.2R.sup.2aS(O).sub.2--,
--S(O).sub.2NR.sup.2--, --NR.sup.2S(O).sub.2--,
--NR.sup.2S(O).sub.2CR.sup.2R.sup.2a--,
--CR.sup.2R.sup.2aS(O).sub.2NR.sup.2--,
--NR.sup.2S(O).sub.2NR.sup.2--, --C(O)NR.sup.2--, --NR.sup.2C(O)--,
--C(O)NR.sup.2CR.sup.2R.sup.2a--, --NR.sup.2C(O)CR.sup.2R.sup.2a--,
--CR.sup.2R.sup.2aC(O)NR.sup.2--, --CR.sup.2R.sup.2aNR.sup.2C(O)--,
--NR.sup.2C(O)O--, --OC(O)NR.sup.2--, --NR.sup.2C(O)NR.sup.2--,
--NR.sup.2--, --NR.sup.2CR.sup.2R.sup.2a--,
--CR.sup.2R.sup.2aNR.sup.2--, O, --CR.sup.2R.sup.2aO-, and
--OCR.sup.2R.sup.2a--; Y is selected from:
CH.sub.2NR.sup.2R.sup.2a; CH.sub.2CH.sub.2NR.sup.2R.sup.2a;
C.sub.3-10 carbocycle substituted with 0-2 R.sup.4a, and, 5-10
membered heterocycle consisting of: carbon atoms and 1-4
heteroatoms selected from the group consisting of N, O, and S
substituted with 0-2 R.sup.4a; Z.sup.2 is selected from H,
C.sub.1-4 alkyl, phenyl, benzyl, C(O)R.sup.3, and
S(O).sub.pR.sup.3c; R.sup.1a is selected from H,
--(CH.sub.2).sub.r--R.sup.1b, --CH.dbd.CH--R.sup.1b,
NCH.sub.2R.sup.1c, OCH.sub.2R.sup.1c, SCH.sub.2R.sup.1c,
NH(CH.sub.2).sub.2(CH.sub.2).sub.tR.sup.1b,
O(CH.sub.2).sub.2(CH.sub.2).s- ub.tR.sup.1b, S(CH.sub.2) 2
(CH.sub.2).sub.tR.sup.1b, S(O) p (CH.sub.2).sub.rR.sup.d,
O(CH.sub.2).sub.rR.sup.1d, NR.sup.3 (CH.sub.2).sub.rR.sup.1d,
OC(O)NR.sup.3(CH.sub.2).sub.rR.sup.1d,
NR.sup.3C(O)NR.sup.3(CH.sub.2).sub.rR.sup.1d,
NR.sup.3C(O)O(CH.sub.2).sub- .rR.sup.1d, and NR.sup.3C(O)
(CH.sub.2).sub.rR.sup.1d, provided that R.sup.1a forms other than
an N-halo, N--N, N--S, N--O, or N--CN bond; R.sup.1b is selected
from H, C.sub.1-3 alkyl, F, Cl, Br, I, --CN, --CHO,
(CF.sub.2).sub.rCF.sub.3, (CH.sub.2).sub.rOR.sup.2,
NR.sup.2R.sup.2a, C(O)R.sup.2c, OC(O)R.sup.2,
(CF.sub.2).sub.rCO.sub.2R.sup.2a, S(O).sub.pR.sup.2b, NR.sup.2
(CH.sub.2).sub.rOR.sup.2, C(.dbd.NR.sup.2c)NR.sup.2R.sup.2a,
NR.sup.2C(O)R.sup.2b, NR.sup.2C(O)NHR.sup.2b,
NR.sup.2C(O).sub.2R.sup.2a, OC(O)NR.sup.2aR.sup.2b,
C(O)NR.sup.2R.sup.2a, C(O)NR.sup.2(CH.sub.2).sub.- rOR.sup.2,
SO.sub.2NR.sup.2R.sup.2a, NR.sup.2SO.sub.2R.sup.2b, C.sub.3-6
carbocycle substituted with 0-2 R.sup.4a, and 5-10 membered
heterocycle consisting of carbon atoms and from 1-4 heteroatoms
selected from the group consisting of N, O, and S substituted with
0-2 R.sup.4a, provided that R.sup.1b forms other than an N-halo,
N--N, N--S, N--O, or N--CN bond; R.sup.1c is selected from H,
CH(CH.sub.2OR.sup.2).sub.2, C(O)R.sup.2c, C(O)NR.sup.2R.sup.2a,
S(O)R.sup.2b, S(O).sub.2R.sup.2b, and SO.sub.2NR.sup.2R.sup.2a;
R.sup.1d is selected from C.sub.3-6 carbocycle substituted with 0-2
R.sup.4a, and 5-10 membered heterocycle consisting of carbon atoms
and from 1-4 heteroatoms selected from the group consisting of N,
O, and S substituted with 0-2 R.sup.4a, provided that R.sup.1d
forms other than an N--N, N--S, or N--O bond; R.sup.2, at each
occurrence, is selected from H, CF.sub.3, C.sub.1-6 alkyl, benzyl,
C.sub.3-6 carbocycle substituted with 0-2 R.sup.4b, a C.sub.3-6
carbocyclic-CH.sub.2-residue substituted with 0-2 R.sup.4b, and 5-6
membered heterocycle consisting of: carbon atoms and 1-4
heteroatoms selected from the group consisting of N, O, and S
substituted with 0-2 R.sup.4b; R.sup.2a, at each occurrence, is
selected from H, CF.sub.3, C.sub.1-6 alkyl, benzyl, C.sub.3-6
carbocycle substituted with 0-2 R.sup.4b, and 5-6 membered
heterocycle consisting of: carbon atoms and 1-4 heteroatoms
selected from the group consisting of N, O, and S substituted with
0-2 R.sup.4b; R.sup.2b, at each occurrence, is selected from
CF.sub.3, C.sub.1-4 alkoxy, C.sub.1-6 alkyl, benzyl, C.sub.3-6
carbocycle substituted with 0-2 R.sup.4b, and 5-6 membered
heterocycle consisting of: carbon atoms and 1-4 heteroatoms
selected from the group consisting of N, O, and S substituted with
0-2 R.sup.4b; R.sup.2c, at each occurrence, is selected from
CF.sub.3, OH, C.sub.1-4 alkoxy, C.sub.1-6 alkyl, benzyl, C.sub.3-6
carbocyclic residue substituted with 0-2 R.sup.4b, and 5-6 membered
heterocyclic system containing from 1-4 heteroatoms selected from
the group consisting of N, O, and S substituted with 0-2 R.sup.4b;
alternatively, R.sup.2 and R.sup.2a, together with the atom to
which they are attached, combine to form a 5 or 6 membered
saturated, partially saturated or unsaturated ring substituted with
0-2 R.sup.4b and consisting of: 0-1 additional heteroatoms selected
from the group consisting of N, O, and S; R.sup.3, at each
occurrence, is selected from H, C.sub.1-4 alkyl, and phenyl;
R.sup.3a, at each occurrence, is selected from H, C.sub.1-4 alkyl,
benzyl, and phenyl; R.sup.3b, at each occurrence, is selected from
H, C.sub.1-4 alkyl, and phenyl; R.sup.3c, at each occurrence, is
selected from C.sub.1-4 alkyl, benzyl, and phenyl; R.sup.3d, at
each occurrence, is selected from H, C.sub.1-4 alkyl, C.sub.1-4
alkyl-phenyl, and C(.dbd.O)R.sup.3c; R.sup.4, at each occurrence,
is selected from H, .dbd.O, (CH.sub.2).sub.rOR.sup.2, F, Cl, Br, I,
C.sub.1-4 alkyl, --CN, NO.sub.2, (CH.sub.2).sub.rNR.sup.2R.sup.2a,
(CH.sub.2).sub.rC(O)R.sup.2c, NR.sup.2C(O)R.sup.2b,
C(O)NR.sup.2R.sup.2a, NR.sup.2C(O)NR.sup.2R.sup.2a, C
(.dbd.NR.sup.2)NR.sup.2R.sup.2a, C
(.dbd.NS(O).sub.2R.sup.5)NR.sup.2R.sup.2a, NHC
(.dbd.NR.sup.2)NR.sup.2R.s- up.2a, C(O)NHC
(.dbd.NR.sup.2)NR.sup.2R.sup.2a, SO.sub.2NR.sup.2R.sup.2a,
NR.sup.2SO.sub.2NR.sup.2R.sup.2a, NR.sup.2SO.sub.2--C.sub.1-4
alkyl, NR.sup.2SO.sub.2R.sup.5, S(O).sub.pR.sup.5,
(CF.sub.2).sub.rCF.sub.3, NCH.sub.2R.sup.1c, OCH.sub.2R.sup.1c,
SCH.sub.2R.sup.1c, N(CH.sub.2) 2 (CH.sub.2).sub.tR.sup.1b,
O(CH.sub.2) 2 (CH.sub.2).sub.tR.sup.1b, and S(CH.sub.2) 2
(CH.sub.2).sub.tR.sup.1b; alternatively, one R.sup.4 is a 5-6
membered aromatic heterocycle consisting of: carbon atoms and 1-4
heteroatoms selected from the group consisting of N, O, and S;
R.sup.4a, at each occurrence, is selected from H, .dbd.O,
(CH.sub.2).sub.rOR.sup.2, (CH.sub.2).sub.r--F,
(CH.sub.2).sub.r--Br, (CH.sub.2).sub.r--Cl, Cl, Br, F, I, C.sub.1-4
alkyl, s-CN, NO.sub.2, (CH.sub.2).sub.rNR.sup.2R.sup.2a,
(CH.sub.2).sub.rC(O)R.sup.2c, NR.sup.2C(O)R.sup.2b,
C(O)NR.sup.2R.sup.2a, (CH.sub.2).sub.rN.dbd.CHOR.sup.3,
C(O)NH(CH.sub.2).sub.2NR.sup.2R.sup.2a,
NR.sup.2C(O)NR.sup.2R.sup.2a, C (.dbd.NR.sup.2)NR.sup.2R.sup.2a,
NHC (.dbd.NR.sup.2)NR.sup.2R.sup.2a, SO.sub.2NR.sup.2R.sup.2a,
NR.sup.2SO.sub.2NR.sup.2R.sup.2a, NR.sup.2SO.sub.2--C.sub.1-4
alkyl, C(O)NHSO.sub.2--C.sub.1-4 alkyl, NR.sup.2SO.sub.2R.sup.5,
S(O).sub.pR.sup.5, and (CF.sub.2).sub.rCF.sub.3; alternatively, one
R.sup.4a is phenyl substituted with 0-1 R.sup.5 or a 5-6 membered
aromatic heterocycle consisting of: carbon atoms and 1-4
heteroatoms selected from the group consisting of N, O, and S
substituted with 0-1 R.sup.5; R.sup.4b, at each occurrence, is
selected from H, .dbd.O, (CH.sub.2).sub.rOR.sup.3, F, Cl, Br, I,
C.sub.1-4 alkyl, --CN, NO.sub.2, (CH.sub.2).sub.rNR.sup.3R.sup.3a,
(CH.sub.2).sub.rC(O)R.sup.3, (CH.sub.2).sub.rC(O)OR.sup.3c,
NR.sup.3C(O)R.sup.3a, C(O)NR.sup.3R.sup.3a,
NR.sup.3C(O)NR.sup.3R.sup.3a, C(.dbd.NR.sup.3)NR.sup.3R.sup.3a,
NR.sup.3C(.dbd.NR.sup.3)NR.sup.3R.sup.3- a,
SO.sub.2NR.sup.3R.sup.3a, NR.sup.3SO.sub.2NR.sup.3R.sup.3a,
NR.sup.3SO.sub.2--C.sub.1-4 alkyl, NR.sup.3SO.sub.2CF.sub.3,
NR.sup.3SO.sub.2-phenyl, S(O).sub.pCF.sub.3, S(O).sub.p--C.sub.1-4
alkyl, S(O).sub.p-phenyl, and (CF.sub.2).sub.rCF.sub.3; R.sup.5, at
each occurrence, is selected from H, C.sub.1-6 alkyl, .dbd.O,
(CH.sub.2).sub.rOR.sup.3, F, Cl, Br, I, C.sub.1-4 alkyl, --CN,
NO.sub.2, (CH.sub.2).sub.rNR.sup.3R.sup.3a,
(CH.sub.2).sub.rC(O)R.sup.3, (CH.sub.2).sub.rC(O)OR.sup.3c,
NR.sup.3C(O)R.sup.3a, C(O)NR.sup.3R.sup.3a,
NR.sup.3C(O)NR.sup.3R.sup.3a, CH(.dbd.NOR.sup.3d),
C(.dbd.NR.sup.3)NR.sup.3R.sup.3a,
NR.sup.3C(.dbd.NR.sup.3)NR.sup.3R.sup.3- a,
SO.sub.2NR.sup.3R.sup.3a, NR.sup.3SO.sub.2NR.sup.3R.sup.3a,
NR.sup.3SO.sub.2--C.sub.1-4 alkyl, NR.sup.3SO.sub.2CF.sub.3,
NR.sup.3SO.sub.2-phenyl, S(O).sub.pCF.sub.3, S(O).sub.p--C.sub.1-4
alkyl, S(O).sub.p-phenyl, (CF.sub.2).sub.rCF.sub.3, phenyl
substituted with 0-2 R.sup.6, naphthyl substituted with 0-2
R.sup.6, and benzyl substituted with 0-2 R.sup.6; R.sup.6, at each
occurrence, is selected from H, OH, (CH.sub.2).sub.rOR.sup.2, halo,
C.sub.1-4 alkyl, CN, NO.sub.2,
(CH.sub.2).sub.rNR.sup.2R.sup.2a,(CH.sub.2).sub.rC(O)R.sup.2b,
NR.sup.2C(O)R.sup.2b, NR.sup.2C(O)NR.sup.2R.sup.2a,
C(.dbd.NH)NH.sub.2, NHC(.dbd.NH)NH.sub.2, SO.sub.2NR.sup.2R.sup.2a,
NR.sup.2SO.sub.2NR.sup.2R- .sup.2a, and NR.sup.2SO.sub.2C.sub.1-4
alkyl; R.sup.7, at each occurrence, is selected from H, OH,
C.sub.1-6 alkyl, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkoxy,
C.sub.1-4 alkoxycarbonyl, (CH.sub.2).sub.n-phenyl, C.sub.6-10
aryloxy, C.sub.6-10 aryloxycarbonyl, C.sub.6-10 arylmethylcarbonyl,
C.sub.1-4 alkylcarbonyloxy C.sub.1-4 alkoxycarbonyl, C.sub.6-10
arylcarbonyloxy C.sub.1-4 alkoxycarbonyl, C.sub.1-6
alkylaminocarbonyl, phenylaminocarbonyl, and phenyl C.sub.1-4
alkoxycarbonyl; R.sup.8, at each occurrence, is selected from H,
C.sub.1-6 alkyl, and (CH.sub.2).sub.n-phenyl; alternatively,
R.sup.7 and R.sup.8 combine to form a 5 or 6 membered saturated,
ring which contains from 0-1 additional heteroatoms selected from
the group consisting of N, O, and S; R.sup.9, at each occurrence,
is selected from H, C.sub.1-6 alkyl, and (CH.sub.2) n-phenyl; n, at
each occurrence, is selected from 0, 1, 2, and 3; p, at each
occurrence, is selected from 0, 1, and 2; r, at each occurrence, is
selected from 0, 1, 2, 3, 4, 5, and 6; s, at each occurrence, is
selected from 0, 1, and 2; and, t, at each occurrence, is selected
from 0, 1, 2, and 3.
9. A compound according to claim 8, wherein: ring M is substituted
with 0-2 R.sup.3 and is selected from the group: 6869Z.sup.2 is
selected from H, C.sub.1-4 alkyl, phenyl, benzyl, C(O)R.sup.3, and
S(O).sub.pR.sup.3c; G is selected from the group: 70717273A is
selected from one of the following carbocyclic and heterocyclic
systems which are substituted with 0-2 R.sup.4; phenyl,
piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl,
thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl,
thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxadiazolyl,
thiadiazolyl, triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl,
1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl,
1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl,
1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl,
benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl,
benzoxazolyl, benzthiazolyl, indazolyl, benzisoxazolyl,
benzisothiazolyl, and isoindazolyl; B is Y or X-Y; X is selected
from C.sub.1-4 alkylene, --C(O)--, --C (.dbd.NR)--,
--CR.sup.2(NR.sup.2R.sup.2a)-, --C(O)CR.sup.2R.sup.2a--,
--CR.sup.2R.sup.2aC(O), --C(O)NR.sup.2--, --NR.sup.2C(O)--,
--C(O)NR.sup.2CR.sup.2R.sup.2a--, --NR.sup.2C(O)CR.sup.2R.sup.2a--,
--CR.sup.2R.sup.2aC(O)NR.sup.2--, --CR.sup.2R.sup.2aNR.sup.2C(O)--,
--NR.sup.2C(O)NR.sup.2--, --NR.sup.2--, NR.sup.2CR.sup.2R.sup.2a--,
CR.sup.2R.sup.2aNR.sup.2--, O, --CR.sup.2R.sup.2aO--, and
--OCR.sup.2R.sup.2a; Y is CH.sub.2NR.sup.2R.sup.2a or
CH.sub.2CH.sub.2NR.sup.2R.sup.2a; alternatively, Y is selected from
one of the following carbocyclic and heterocyclic systems that are
substituted with 0-2 R.sup.4a; cyclopropyl, cyclopentyl,
cyclohexyl, phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl,
furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl,
isoxazolyl, isoxazolinyl, thiazolyl, isothiazolyl, pyrazolyl,
imidazolyl, oxadiazolyl, thiadiazolyl, triazolyl,
1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,
1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,
1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl,
1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl,
benzothiofuranyl, indolyl, benzimidazolyl, benzoxazolyl,
benzthiazolyl, indazolyl, benzisoxazolyl, benzisothiazolyl, and
isoindazolyl; alternatively, Y is selected from the following
bicyclic heteroaryl ring systems: 74K is selected from O, S, NH,
and N.
10. A compound according to claim 9, wherein: ring M is substituted
with 0-2 R.sup.3 and is selected from the group: 7576G is selected
from the group: 7778
11. A compound according to claim 10, wherein: ring M is
substituted with 0-1 R.sup.3 and is selected from the group: 79G is
selected from: 80
12. A compound according to claim 11, wherein: A is selected from
phenyl, pyridyl, and pyrimidyl, and is substituted with 0-2
R.sup.4; and, B is selected from phenyl, pyrrolidino,
N-pyrrolidino-carbonyl, morpholino, N-morpholino-carbonyl,
1,2,3-triazolyl, imidazolyl, and benzimidazolyl, and is substituted
with 0-1 R.sup.4a; R.sup.2, at each occurrence, is selected from H,
CH.sub.3, CH.sub.2CH.sub.3, cyclopropylmethyl, cyclobutyl, and
cyclopentyl; R.sup.2a, at each occurrence, is H or CH.sub.3;
alternatively, R.sup.2 and R.sup.2a, together with the atom to
which they are attached, combine to form pyrrolidine substituted
with 0-2 R.sup.4b; R.sup.4, at each occurrence, is selected from
OH, (CH.sub.2).sub.rOR.sup.2, halo, C.sub.1-4 alkyl,
(CH.sub.2).sub.rNR.sup.2- R.sup.2a, and (CF.sub.2).sub.rCF.sub.3;
R.sup.4a is selected from C.sub.1-4 alkyl, CF.sub.3,
(CH.sub.2).sub.rOR.sup.2, (CH.sub.2).sub.rNR.sup.2R.sup.2a,
S(O).sub.pR.sup.5, SO.sub.2NR.sup.2R.sup.2a, and
1-CF.sub.3-tetrazol-2-yl; R.sup.4b, at each occurrence, is selected
from H, CH.sub.3, and OH; R.sup.5, at each occurrence, is selected
from CF.sub.3, C.sub.1-6 alkyl, phenyl, and benzyl; and, r, at each
occurrence, is selected from 0, 1, and 2.
13. A compound according to claim 12, wherein: A is selected from
the group: phenyl, 2-pyridyl, 3-pyridyl, 2-pyrimidyl, 2-Cl-phenyl,
3-Cl-phenyl, 2-F-phenyl, 3-F-phenyl, 2-methylphenyl, 2-aminophenyl,
and 2-methoxyphenyl; and, B is selected from the group:
2-(aminosulfonyl)phenyl, 2-(methylaminosulfonyl)phenyl,
1-pyrrolidinocarbonyl, 2-(methylsulfonyl)phenyl,
2-(N,N-dimethylaminometh- yl)phenyl,
2-(N-pyrrolidinylmethyl)phenyl, 1-methyl-2-imidazolyl,
2-methyl-1-imidazolyl, 2-(dimethylaminomethyl)-1-imidazolyl,
2-(N-(cyclopropylmethyl)aminomethyl)phenyl,
2-(N-(cyclobutyl)aminomethyl)- phenyl,
2-(cyclopentyl)aminomethyl)phenyl, and 2-(N-(3-hydroxypyrrolidinyl-
)methyl)phenyl.
14. A compound according to claim 8, wherein the compound is
selected from:
7-(3-aminomethyl-phenyl)-1-(2'-methanesulfonyl-biphenyl-4-yl)-3-pro-
pyl-3,7-dihydro-purine-2,6 dione;
1-(4-methoxyphenyl)-6-{2'-[aminomethyl]--
1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(methylamino)methyl]-1,1'-biphenyl-4-yl}-7-oxo-
-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-
-[(dimethylamino)methyl]-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-i-
midazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(N-ethyl-N-methylamino-
)methyl]-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]p-
yridine;
1-(4-methoxyphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'-b-
iphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-biphenyl-4-yl}-7--
oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7--
oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(4-me-
thoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(4-me-
thoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(4-methoxyp-
henyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(4-methoxyphenyl)-7-oxo-4,5-
,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(4-{2-[(dimethylamino)methy-
l]-1H-imidazol-1-yl}phenyl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1-
H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-[4-(2-methyl-1H-imidazol-
-1-yl)phenyl]-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(4-me-
thoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(4-methoxyphe-
nyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}phenyl-
)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-
-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-methylsulfonyl-1,1'-bipheny-
l-4-yl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]py-
ridine;
1-(4-methoxyphenyl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-biphenyl-4-y-
l}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-biphenyl-4--
yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-biphenyl--
4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-fluoro-1,1'-b-
iphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fluoro-1,1'--
biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro
1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1'-biphenyl-
-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxyph-
enyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl]-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine-
;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-y-
l)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridin-
e;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl}-1--
(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(4-methoxyphenyl)-
-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-1-(4-m-
ethoxyphenyl)-7-oxo-4,5,6,7-tetrahydro 1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-phenyl]-7-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl-
)(methyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7--
oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-m-
ethoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-2-flu-
oro-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-ox-
o-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-methylsulfonyl-3-f-
luoro-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H--
imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-1,1'-
-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(methylamino)methyl]-1,1'-biphenyl-4-yl}-7-
-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(dimethylamino)methyl]-1,1'-biphenyl-4-yl}-
-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-2'-[(N-ethyl-N-methylamino)methyl]-1,1'-bipheny-
l-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'-biphe-
nyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-biphenyl-4-yl-
}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl-
)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-am-
inomethylphenyl)-7-oxo-4,5,6,7-tetrahydro
1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-am-
inomethylphenyl)-7-oxo-4,5,6,7-tetrahydro
1H-imidazolo[4,5-c]pyridine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3-aminomet-
hylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(3-aminomethylphenyl)-7-oxo-
-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(4-{2-[(dimethylamino)m-
ethyl]-1H-imidazol-1-yl}phenyl)-1-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetr-
ahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-[4-(2-methyl-
-1H-imidazol-1-yl)phenyl]-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyri-
dine;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1--
(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro
1H-imidazolo[4,5-c]pyridine- ;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminometh-
ylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}ph-
enyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-7-oxo-4,5-
,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-methylsulfonyl-1,1'-bip-
henyl-4-yl)-1-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[-
4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-3-fluoro-1,1'--
biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-bipheny-
l-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-biphe-
nyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-fluoro-1,-
1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fluoro-1-
,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1'-biph-
enyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomet-
hylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyri-
dine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl]-3-fluoro-1,1'-biphenyl-
-4-yl)-1-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c-
]pyridine;
6-[(2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-
-4-yl}-1-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c-
]pyridine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(3-amin-
omethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl]-2-fluoro-phenyl)-1-(3-a-
minomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminomethylphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-phenyl]-
-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyri-
dine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-
-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridin-
e;
1-(3-aminomethylphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-
-2-fluoro-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)--
7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-
-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-7-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol--
5'-yl)-6-{2'-[(methylamino)methyl]-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetra-
hydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(d-
imethylamino)methyl]-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imida-
zolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methy-
lamino)methyl]-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4-
,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamin-
o)methyl]-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]-
pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-1,1-
'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-
-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-am-
inobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridin-
e;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1;1'-biphenyl-4-yl)-1-(3--
aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyrid-
ine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3-amin-
obenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro
1H-imidazolo[4,5-c]pyridine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(3-aminobenzisoxazol-5'-yl)-
-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}phenyl)-1-(3-aminobenzis-
oxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro 1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-7-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl-
)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-
-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminobenzi-
soxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-
-yl}phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
6-(2'-methylsulfonyl-1,-
1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1-
H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[aminometh-
yl]-3-fluoro-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-
-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(methylamino)methyl]-3-f-
luoro-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyri-
dine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-
-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro
1H-imidazolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-flu-
oro-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridi-
ne;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-
-fluoro-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]py-
ridine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-3-flu-
oro-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridi-
ne;
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-amino-
benzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro
1H-imidazolo[4,5-c]pyridine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5--
c]pyridine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bi-
phenyl-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imi-
dazolo[4,5-c]pyridine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,-
1'-biphenyl-4-yl}-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1-
H-imidazolo[4,5-c]pyridine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro--
phenyl}-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazol-
o[4,5-c]pyridine;
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluo-
ro-phenyl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imida-
zolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(2-methyl-1H-imida-
zol-1-yl)-2-fluoro-phenyl]-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyr-
idine;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazol-
o[4,5-c]pyridine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biph-
enyl-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imida-
zolo[4,5-c]pyridine;
1-(3-aminobenzisoxazol-5'-yl)-6-(4-{2-[(methylamino)m-
ethyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imid-
azolo[4,5-c]pyridine;
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(-
3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyr-
idine;
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminobenziso-
xazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
3-[4,5,6,7-tetrahydro-6-[2'-[aminomethyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-i-
midazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[methy-
lamino]methyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]-
benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[dimethylamino]methyl][1,1'-biphen-
yl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[4-hydroxypiperidin-1-yl]methyl][1,1'-biphen-
yl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[N-ethyl-N-methylamino]-methyl][1,1'-bipheny-
l]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[pyrrolidin-1-yl]methyl][1,1'-biphenyl]-4-yl-
]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-
-[2'-[[3(R)-hydroxypyrrolidin-1-yl]methyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-i-
midazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[3(S)--
hydroxypyrrolidin-1-yl]methyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-
-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[N-propyl-N-methyl-
amino]-methyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]-
benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[t-butylamino]methyl][1,1'-bipheny-
l]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-7-oxo-1-
H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(4-{2-[(-
dimethylamino)methyl]-1H-imidazol-1-yl}phenyl)-7-oxo-1H-imidazolo[4,5-c]py-
ridin 1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[4-(2-methyl-1H-imidazol-1-y-
l)phenyl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'--
biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-
-4-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}phen-
yl)-7-oxo-1H-imidazolo[4,5-c]pyridin 1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-7-oxo-1H-im-
idazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(2'-methylsu-
lfonyl-1,1'-biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide-
;
3-[4,5,6,7-tetrahydro-6-[2'-[aminomethyl]-3-fluoro-[1,1'-biphenyl]-4-yl]-
-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6--
[2'-[[methylamino]methyl]-3-fluoro[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo-
[4,5-c]pyridin 1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[dimethylamino-
]methyl]-3-fluoro-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-
-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[4-hydroxypiperidin-1-yl]methy-
l]-3-fluoro-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]be-
nzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[N-ethyl-N-methylamino]methyl]-3-flu-
oro-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[pyrrolidin-1-yl]methyl]-3-fluoro-[1,1'-biph-
enyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7--tetrahydro-6-[2'-[[3(R)-hydroxypyrrolidin-1-yl]methyl]-3-fluo-
ro-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[3(S)-hydroxypyrrolidin-1-yl]methyl]-3-fluor-
o-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[N-propyl-N-methylamino]-methyl]-3-fluoro-[1-
,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[t-butylamino]methyl]-3-fluoro[1,1'-biphenyl-
]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin 1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-pheny-
l}-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-
-fluoro-phenyl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-phenyl]-7-
-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(2-
'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-7-o-
xo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(2'--
{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-7-oxo-1H-imid-
azolo[4,5-c]pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(4-{2-[(methyl-
amino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-7-oxo-1H-imidazolo[4,5-c]-
pyridin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(2'-aminosulfonyl-3-fluoro-
-1,1'-biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
and,
3-[4,5,6,7-tetrahydro-6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-7-
-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide; or a
pharmaceutically acceptable salt form thereof.
15. A compound according to claim 8, wherein the compound is
selected from:
1-(4-Methoxyphenyl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-oxo-1,6-
-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(4-Methoxyphenyl)-6-{2'-[(methyl-
amino)methyl]-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyr-
imidine;
1-(4-Methoxyphenyl)-6-{2'-[(dimethylamino)methyl]-1,1'-biphenyl-4-
-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(4-Methoxyphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-1,1'-biphenyl-4-
-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(4-Methoxyphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'-biphenyl--
4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(4-Methoxyphenyl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-biphenyl-4-yl}-7--
oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[1-pyrrolidinyl]meth-
yl}-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo-
[4,5-d]pyrimidine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biph-
enyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimi-
dine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1--
(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(4-methoxyp-
henyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(4-methoxyphenyl)-7-oxo-1,6-
-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(4-{2-[(dimethylamino)methyl]-1H-
-imidazol-1-yl}phenyl)-1-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[-
4,5-d]pyrimidine;
1-(4-methoxyphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)phen-
yl]-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(4-me-
thoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(4-methoxyphe-
nyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}phenyl-
)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-aminosulfonyl-1,1-
'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]-
pyrimidine;
6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-
-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(4-Methoxyphenyl)-6-{2'--
[aminomethyl]-3-fluoro-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[-
4,5-d]pyrimidine;
1-(4-Methoxyphenyl)-6-{2'-[(methylamino)methyl]-3-fluoro-
-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(4-Methoxyphenyl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-biphenyl--
4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(4-Methoxyphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-fluoro-1,1'-b-
iphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(4-Methoxyphenyl)-6-2'-[(N-methyl-N-propylamino)methyl]-3-fluoro-1,1'-b-
iphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(4-Methoxyphenyl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1'-biphenyl-
-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxyp-
henyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl}-1-(4-
-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(4-methoxyphenyl)-
-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(4-{2-[(dimethylamino)-
methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-1-(4-methoxyphenyl)-7-oxo-1,6-d-
ihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(4-methoxyphenyl)-6-[4-(2-methyl-1-
H-imidazol-1-yl)-2-fluoro-phenyl]-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyr-
imidine;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-biphe-
nyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimid-
ine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1--
(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-2-flu-
oro-phenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-ox-
o-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-methylsulfonyl-3-fluoro-
-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,-
5-d]pyrimidine;
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-1,1'-biphenyl--
4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminomethylphenyl)-6-{2'-[(methylamino)methyl]-1,1'-biphenyl-4-yl}-7-
-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminomethylphenyl)-6--
{2'-[(dimethylamino)methyl]-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imida-
zolo[4,5 d]pyrimidine;
1-(3-aminomethylphenyl)-6-{2'-[(N-ethyl-N-methylami-
no)methyl]-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimi-
dine;
1-(3-aminomethylphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'--
biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-biphenyl-4-yl-
}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[1-pyrrolidinyl]-
methyl}-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-i-
midazolo[4,5-d]pyrimidine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1-
,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[-
4,5-d]pyrimidine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphe-
nyl-4-yl)-1-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyr-
imidine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3--
aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(3-aminomethylphenyl)-7-oxo-
-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(4-{2-[(dimethylamino)methyl-
]-1H-imidazol-1-yl}phenyl)-1-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-im-
idazolo[4,5-d]pyrimidine;
1-(3-aminomethylphenyl)-6-[4-(2-methyl-1H-imidaz-
ol-1-yl)phenyl]-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-am-
inomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminomethy-
lphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminomethylphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}ph-
enyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-7-oxo-1,6-
-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-methylsulfonyl-1,1'-biphenyl-
-4-yl)-1-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimi-
dine;
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-biphenyl-4-
-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminomethylphenyl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-bipheny-
l-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminomethylphenyl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-biphe-
nyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminomethylphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-fluoro-1,-
1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminomethylphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fluoro-1-
,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1'-biph-
enyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomet-
hylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl}-1-(3-
-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(3-aminomethylphe-
nyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-1-(3-a-
minomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminomethylphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-phenyl]-
-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[(2-hydroxyethyl)-
(methyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-
-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[(2-hydroxyethyl)-
amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-7-oxo-1-
,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminomethylphenyl)-6-(4-{2--
[(methylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-7-oxo-1,6-dihydro-
-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-
-4-yl)-1-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimi-
dine;
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylph-
enyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-7-o-
xo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminobenzisoxazol-5'-yl-
)-6-{2'-[(methylamino)methyl]-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imi-
dazolo[4,5-d]pyrimidine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(dimethylami-
no)methyl]-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimi-
dine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methylamino)methyl]--
1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'-
-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-bipheny-
l-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-
-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-am-
inobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-am-
inobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-[2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3-aminoben-
zisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(3-aminobenzisoxazol-5'-yl)-
-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(4-{2-[(dimethylamino)-
methyl]-1H-imidazol-1-yl}phenyl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-d-
ihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(-
2-methyl-1H-imidazol-1-yl)phenyl]-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyr-
imidine;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-
-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimi-
dine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-amino-
benzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminobenzisoxazol-5'-yl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-
-yl}phenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-o-
xo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-methylsulfonyl-1,1'-bi-
phenyl-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[-
4,5-d]pyrimidine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[aminomethyl]-3-fluo-
ro-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-b-
iphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-
-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-flu-
oro-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fl-
uoro-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1-
'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminoben-
zisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrim-
idine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d-
]pyrimidine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-bipheny-
l-4-yl}-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d-
]pyrimidine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(3-am-
inobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-1-(3-a-
minobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-p-
henyl]-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrim-
idine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)--
1-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimid-
ine;
1-(3-aminobenzisoxazol-5'-yl)-6-(4-{2-[(methylamino)methyl]-1H-imidaz-
ol-1-yl}-2-fluoro-phenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5-
'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol--
5'-yl)-7-oxo-1,6-dihydro-1H imidazolo[4,5-d]pyrimidine;
3-[1,6-dihydro-6-[2'-[aminomethyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazol-
o[4,5-d]pyrimidin-1-yl]benzamide;
3-[(1,6-dihydro-6-[2'-[[methylamino]meth-
yl][1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide-
;
3-[(1,6-dihydro-6-(2'-[[dimethylamino]methyl][1,1'-biphenyl]-4-yl]-7-oxo-
-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[2'-[[4-hyd-
roxypiperidin-1-yl]methyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]p-
yrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[2'-[[N-ethyl-N-methylamino]meth-
yl][1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide-
;
3-[1,6-dihydro-6-[2'-[[pyrrolidin-1-yl]methyl][1,1'-biphenyl]-4-yl]-7-ox-
o-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[2'-[[3(R)-
-hydroxypyrrolidin-1-yl]methyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,-
5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[2'-[[3(S)-hydroxypyrrolidi-
n-1-yl]methyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-y-
l]benzamide;
3-[1,6-dihydro-6-[2'-[[N-propyl-N-methylamino]methyl][1,1'-bi-
phenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[2'-[[t-butylamino]methyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-
-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-{4-[3-(aminosu-
lfonyl)-4-pyridinyl]phenyl}-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzam-
ide;
3-[1,6-dihydro-6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}pheny-
l)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-7-oxo-1H-imidazolo-
[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-(2'-{[(2-hydroxyethyl)(m-
ethyl)amino]methyl}-1,1'-biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-
-1-yl]benzamide;
3-[1,6-dihydro-6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-
-biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}phenyl)-7-o-
xo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-(2'-amino-
sulfonyl-1,1'-biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benza-
mide;
3-[1,6-dihydro-6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-7-oxo-1H-imi-
dazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[2'-[aminomethyl]--
3-fluoro-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]ben-
zamide;
3-[1,6-dihydro-6-[2'-[[methylamino]methyl]-3-fluoro-[1,1'-biphenyl-
]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[2'-[[dimethylamino]methyl]-3-fluoro-[1,1'-biphenyl]-4-y-
l]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[2'-[[4-hydroxypiperidin-1-yl]methyl]-3-fluoro-[1,1'-bip-
henyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[2'-[[N-ethyl-N-methylamino]methyl]-3-fluoro-[1,1'-biphe-
nyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[2'-[[pyrrolidin-1-yl]methyl]-3-fluoro[1,1'-biphenyl]-4--
yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[2'-[[3(R)-hydroxypyrrolidin-1-yl]methyl]-3-fluoro-[1,1'-
-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[2'-[[3(S)-hydroxypyrrolidin-1-yl]methyl]-3-fluoro-[1,1'-
-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[2'-[[N-propyl-N-methylamino]methyl]-3-fluoro-[1,1'-biph-
enyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[2'-[[t-butylamino]methyl]-3-fluoro-[1,1'-biphenyl]-4-yl-
]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-7-ox-
o-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-(4-{2-[(di-
methylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-7-oxo-1H-imidazolo[-
4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-[4-(2-methyl-1H-imidazol--
1-yl)-2-fluoro-phenyl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1-
'-biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-lyl]benzamide;
3-[1,6-dihydro-6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphen-
yl-4-yl)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-p-
henyl)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-7-oxo-1H--
imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
3-[1,6-dihydro-6-(2'-methylsulfo-
nyl-3-fluoro-1,1'-biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]b-
enzamide; or a pharmaceutically acceptable salt form thereof.
16. A compound according to claim 8, wherein the compound is
selected from:
1-(4-methoxyphenyl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-8-oxo-4-
,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(4-methoxyphenyl)-6-{2'-[(-
methylamino)methyl]-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidaz-
olo[4,5-c]azepine;
1-(4-methoxyphenyl)-6-{2'-[(dimethylamino)methyl]-1,1'--
biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(4-methoxyphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-1,1'-biphenyl-4-
-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(4-methoxyphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'-biphenyl--
4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(4-methoxyphenyl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-biphenyl-4-yl}-8--
oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[1-pyrrolidinyl]-
methyl}-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1-
H-imidazolo[4,5-c]azepine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1-
,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazo-
lo[4,5-c]azepine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphe-
nyl-4-yl)-1-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]-
azepine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(4--
methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(4-methoxyphenyl)-8-oxo-4,5-
,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(4-{2-[(dimethylamino)methyl-
]-1H-imidazol-1-yl}phenyl)-1-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-
-imidazolo[4,5-c]azepine;
1-(4-methoxyphenyl)-6-[4-(2-methyl-1H-imidazol-1-
-yl)phenyl]-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(4-me-
thoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(4-methoxyphe-
nyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}phenyl-
)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-8-oxo-4,5,6,7-
-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-methylsulfonyl-1,1'-biphenyl-
-4-yl)-1-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]aze-
pine;
1-(4-methoxyphenyl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-biphenyl-4-yl}-
-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(4-methoxyphenyl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-biphenyl-4--
yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(4-methoxyphenyl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-biphenyl--
4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(4-methoxyphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-fluoro-1,1'-b-
iphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(4-methoxyphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fluoro-1,1'--
biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro 1H-imidazolo[4,5-c]azepine;
1-(4-methoxyphenyl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1'-biphenyl-
-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxyp-
henyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl}-1-(4-
-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(4-methoxyphenyl)-
-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-1-(4-m-
ethoxyphenyl)-8-oxo-4,5,6,7-tetrahydro 1H-imidazolo[4,5-c]azepine;
1-(4-methoxyphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-phenyl]-8-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[(2-hydroxyethyl)-
(methyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-8-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[(2-hydroxyethyl)-
amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-8-oxo-4,5,6-
,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(4-methoxyphenyl)-6-(4-{2-[(me-
thylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-8-oxo-4,5,6,7-tetrahy-
dro-1H-imidazolo[4,5-c]azepine;
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-
-4-yl)-1-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]aze-
pine;
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl-
)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-8-oxo-4,5-
,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminomethylphenyl)-6-{2'--
[(methylamino)methyl]-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imid-
azolo[4,5-c]azepine;
1-(3-aminomethylphenyl)-6-{2'-[(dimethylamino)methyl]-
-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminomethylphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-1,1'-biphen-
yl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminomethylphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'-biphe-
nyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-biphenyl-4-yl-
}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl-
)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-am-
inomethylphenyl)-8-oxo-4,5,6,7-tetrahydro
1H-imidazolo[4,5-c]azepine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-am-
inomethylphenyl)-8-oxo-4,5,6,7-tetrahydro
1H-imidazolo[4,5-c]azepine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3-aminomet-
hylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(3-aminomethylphenyl)-8-oxo-
-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(4-{2-[(dimethylamino)me-
thyl]-1H-imidazol-1-yl}phenyl)-1-(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetra-
hydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminomethylphenyl)-6-[4-(2-methyl-1-
H-imidazol-1-yl)phenyl]-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepin-
e;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3--
aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro
1H-imidazolo[4,5-c]azepine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminomethy-
lphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminomethylphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}ph-
enyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-8-oxo-4,5-
,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-methylsulfonyl-1,1'-biph-
enyl-4-yl)-1-(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4-
,5-c]azepine;
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-bi-
phenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminomethylphenyl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-bipheny-
l-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminomethylphenyl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-biphe-
nyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminomethylphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-fluoro-1,-
1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminomethylphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fluoro-1-
,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1'-biph-
enyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomet-
hylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azep-
ine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl--
4-yl)-1-(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]-
azepine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4--
yl}-1-(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]az-
epine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(3-aminomet-
hylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-1-(3-a-
minomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminomethylphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-phenyl]-
-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azep-
ine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1--
(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminomethylphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-2-
-fluoro-phenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)--
8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-
-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-8-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminobenzisoxazol-5-
'-yl)-6-{2'-[(methylamino)methyl]-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrah-
ydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(dim-
ethylamino)methyl]-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazo-
lo[4,5-c]azepine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methylam-
ino)methyl]-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5--
c]azepine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamino)me-
thyl]-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azep-
ine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-bip-
henyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-
-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-am-
inobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine-
;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-a-
minobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepin-
e;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3-aminob-
enzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro
1H-imidazolo[4,5-c]azepine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(3-aminobenzisoxazol-5'-yl)-
-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}phenyl)-1-(3-aminobenzis-
oxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro 1H-imidazolo[4,5-c]azepine;
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-8-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[(2-hydroxyethyl)-
(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-8--
oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[(2-hydroxyethyl-
)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5-
,6,7-tetrahydro 1H-imidazolo[4,5-c]azepine;
1-(3-aminobenzisoxazol-5'-yl)--
6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}phenyl)-8-oxo-4,5,6,7-tetra-
hydro-1H-imidazolo[4,5-c]azepine;
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)--
1-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]-
azepine;
6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5-
'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-biphenyl--
4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-b-
iphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-
-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro
1H-imidazolo[4,5-c]azepine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-flu-
oro-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepin-
e;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3--
fluoro-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]aze-
pine;
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-3-fluor-
o-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminoben-
zisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro
1H-imidazolo[4,5-c]azepine;
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5--
c]azepine;
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bip-
henyl-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imid-
azolo[4,5-c]azepine;
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-
-biphenyl-4-yl}-1-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H--
imidazolo[4,5-c]azepine;
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phe-
nyl}-1-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4-
,5-c]azepine;
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-p-
henyl)-1-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo-
[4,5-c]azepine;
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(2-methyl-1H-imidazol-1-
-yl)-2-fluoro-phenyl]-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl-
)-1-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5--
c]azepine;
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4--
yl)-1-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,-
5-c]azepine;
1-(3-aminobenzisoxazol-5'-yl)-6-(4-{2-[(methylamino)methyl]-1-
H-imidazol-1-yl}-2-fluoro-phenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,-
5-c]azepine;
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminobe-
nzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol--
5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
3-[4,5,6,7-tetrahydro-6-[2'-[aminomethyl][1,1'-biphenyl]-4-yl]-8-oxo-1H-i-
midazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[methyl-
amino]methyl][1,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]be-
nzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[dimethylamino]methyl][1,1'-biphenyl-
]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[4-hydroxypiperidin-1-yl]methyl][1,1'-biphen-
yl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[N-ethyl-N-methylamino]-methyl][1,1'-bipheny-
l]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[pyrrolidin-1-yl]methyl][1,1'-biphenyl]-4-yl-
]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6--
[2'-[[3(R)-hydroxypyrrolidin-1-yl]methyl][1,1'-biphenyl]-4-yl]-8-oxo-1H-im-
idazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[3(S)-hy-
droxypyrrolidin-1-yl]methyl][1,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c-
]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[N-propyl-N-methylami-
no]-methyl][1,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benz-
amide;
3-[4,5,6,7-tetrahydro-6-[2'-[[t-butylamino]methyl][1,1'-biphenyl]-4-
-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-8-oxo-1-
H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(4-{2-[(d-
imethylamino)methyl]-1H-imidazol-1-yl}phenyl)-8-oxo-1H-imidazolo[4,5-c]aze-
pin 1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[4-(2-methyl-1H-imidazol-1-yl)-
phenyl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'--
biphenyl-4-yl)-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-
-4-yl)-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}phen-
yl)-8-oxo-1H-imidazolo[4,5-c]azepin 1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-8-oxo-1H-im-
idazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(2'-methylsul-
fonyl-1,1'-biphenyl-4-yl)-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[aminomethyl]-3-fluoro-[1,1'-biphenyl]-4-yl]--
8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2-
'-[[methylamino]methyl]-3-fluoro[1,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4-
,5-c]azepin 1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[dimethylamino]me-
thyl]-3-fluoro-[1,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]-
benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[4-hydroxypiperidin-1-yl]methyl]-3-
-fluoro-[1,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzami-
de;
3-[4,5,6,7-tetrahydro-6-[2'-[[N-ethyl-N-methylamino]methyl]-3-fluoro-[-
1,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[pyrrolidin-1-yl]methyl]-3-fluoro-[1,1'-biph-
enyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[3(R)-hydroxypyrrolidin-1-yl]methyl]-3-fluor-
o-[1,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[3(S)-hydroxypyrrolidin-1-yl]methyl]-3-fluor-
o-[1,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[N-propyl-N-methylamino]-methyl]-3-fluoro-[1-
,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[2'-[[t-butylamino]methyl]-3-fluoro[1,1'-biphenyl-
]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin 1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-pheny-
l}-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-
-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)-8-oxo-1H-
-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-[4-(2-meth-
yl-1H-imidazol-1-yl)-2-fluoro-phenyl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl-
]benzamide;
3-[4,5,6,7-tetrahydro-6-(2'-{[(2-hydroxyethyl)(methyl)amino]me-
thyl}-3-fluoro-1,1'-biphenyl-4-yl)-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]be-
nzamide;
3-[4,5,6,7-tetrahydro-6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-flu-
oro-1,1'-biphenyl-4-yl)-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-2-f-
luoro-phenyl)-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-8--
oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
3-[4,5,6,7-tetrahydro-6-(2'--
methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-8-oxo-1H-imidazolo[4,5-c]azepi-
n-1-yl]benzamide; or a pharmaceutically acceptable salt form
thereof.
17. A pharmaceutical composition, comprising: a pharmaceutically
acceptable carrier and a therapeutically effective amount of a
compound of claim 1 or a pharmaceutically acceptable salt form
thereof.
18. A method for treating a thromboembolic disorder, comprising:
administering to a patient in need thereof a therapeutically
effective amount of a compound of claim 1 or a pharmaceutically
acceptable salt form thereof.
Description
CROSS-REFERENCED APPLICATIONS
[0001] This application is a divisional of U.S. application Ser.
No. 09/898,279, filed Jul. 3, 2001, now allowed, which is a
continuation in part of U.S. application Ser. No. 09/470,326, now
U.S. Pat. No. 6,413,980, which claims the benefit of U.S.
Provisional Application No. 60/127,633, filed Apr. 2, 1999, now
abandoned and U.S. Provisional Application No. 60/113,628, filed
Dec. 23, 1998, now abandoned. The contents of each application are
incorporated herein by reference.
FIELD OF THE INVENTION
[0002] This invention relates generally to imidazo-heterobicycles,
which are inhibitors of trypsin-like serine protease enzymes,
especially factor Xa, pharmaceutical compositions containing the
same, and methods of using the same as anticoagulant agents for
treatment and prevention of thromboembolic disorders.
BACKGROUND OF THE INVENTION
[0003] WO94/20460 describes angiotensin II compounds of the
following formula: 2
[0004] wherein X can be a number of substituents and Het can be a
nitrogen-containing heterobicycle. However, WO94/20460 does not
suggest Factor Xa inhibition or exemplify compounds like those of
the present invention.
[0005] WO96/12720 describes phosphodiesterase type IV and TNF
production inhibitors of the following formula: 3
[0006] wherein X can be oxygen and R.sup.2 and R.sup.3 can a number
of substituents including heterocycle, heterocycloalkyl, and
phenyl. However, the presently claimed compounds do not correspond
to the compounds of WO96/12720. Furthermore, WO96/12720 does not
suggest Factor Xa inhibition.
[0007] WO98/52948 describes inhibitors of ceramide-mediated signal
transduction. One of the types of inhibitors described is of the
following formula: 4
[0008] wherein Y.sub.1 can be N--R.sub.6, R.sub.6 can be
unsubstituted aryl-alkyl or unsubstituted heterocyclic-alkyl and
R.sub.1 can be a substituted aryl group. WO98/52948 does not
mention factor Xa inhibition or show compounds like those of the
present invention.
[0009] U.S. Pat. Nos. 3,365,459 and 3,340,269 illustrates
anti-inflammatory inhibitors of the following formula: 5
[0010] wherein A is 2-3 carbon atoms, X can be O, and R.sup.1 and
R.sup.3 can be substituted or unsubstituted aromatic groups.
Neither of these patents, however, exemplify compounds of the
present invention.
[0011] Activated factor Xa, whose major practical role is the
generation of thrombin by the limited proteolysis of prothrombin,
holds a central position that links the intrinsic and extrinsic
activation mechanisms in the final common pathway of blood
coagulation. The generation of thrombin, the final serine protease
in the pathway to generate a fibrin clot, from its precursor is
amplified by formation of prothrombinase complex (factor Xa, factor
V, Ca.sup.2+ and phospholipid). Since it is calculated that one
molecule of factor Xa can generate 138 molecules of thrombin
(Elodi, S., Varadi, K.: Optimization of conditions for the
catalytic effect of the factor IXa-factor VIII Complex: Probable
role of the complex in the amplification of blood coagulation.
Thromb. Res. 1979, 15, 617-629), inhibition of factor Xa may be
more efficient than inactivation of thrombin in interrupting the
blood coagulation system.
[0012] Therefore, efficacious and specific inhibitors of factor Xa
are needed as potentially valuable therapeutic agents for the
treatment of thromboembolic disorders. It is thus desirable to
discover new factor Xa inhibitors.
SUMMARY OF THE INVENTION
[0013] Accordingly, one object of the present invention is to
provide novel imidazo-heterobicycles that are useful as factor Xa
inhibitors or pharmaceutically acceptable salts or prodrugs
thereof.
[0014] It is another object of the present invention to provide
pharmaceutical compositions comprising a pharmaceutically
acceptable carrier and a therapeutically effective amount of at
least one of the compounds of the present invention or a
pharmaceutically acceptable salt or prodrug form thereof.
[0015] It is another object of the present invention to provide a
method for treating thromboembolic disorders comprising
administering to a host in need of such treatment a therapeutically
effective amount of at least one of the compounds of the present
invention or a pharmaceutically acceptable salt or prodrug form
thereof.
[0016] It is another object of the present invention to provide
novel bicyclic compounds for use in therapy.
[0017] It is another object of the present invention to provide the
use of novel bicyclic compounds for the manufacture of a medicament
for the treatment of a thromboembolic disorder.
[0018] These and other objects, which will become apparent during
the following detailed description, have been achieved by the
inventors' discovery that the presently claimed bicyclic compounds,
or pharmaceutically acceptable salt or prodrug forms thereof, are
effective factor Xa inhibitors.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0019] [1] Thus, in an embodiment, the present invention provides a
novel compound of formula I: 6
[0020] or a stereoisomer or pharmaceutically acceptable salt
thereof, wherein;
[0021] G is a group of formula IIa or IIb: 7
[0022] ring D, including the two atoms of Ring E to which it is
attached, is a 5-6 membered non-aromatic ring consisting of carbon
atoms, 0-1 double bonds, and from 0-2 N, and D is substituted with
0-2 R, provided that when ring D is unsubstituted, it contains at
least one heteroatom;
[0023] alternatively, ring D, including the two atoms of Ring E to
which it is attached, is a 5-6 membered aromatic system consisting
of carbon atoms and from 0-2 heteroatoms selected from the group
consisting of N, O, and S, and D is substituted with 0-2 R,
provided that when ring D is unsubstituted, it contains at least
one heteroatom;
[0024] E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl,
and pyridazinyl, and is substituted with 0-1 R;
[0025] R is selected from F, Cl, Br, I, OH, OCH.sub.3,
OCH.sub.2CH.sub.3, OCH(CH.sub.3).sub.2, OCH.sub.2CH.sub.2CH.sub.3,
NH.sub.2, NH(C.sub.1-3 alkyl), N(C.sub.1-3 alkyl).sub.2,
C(.dbd.NH)NH.sub.2, CH.sub.2NH.sub.2, CH.sub.2NH(C.sub.1-3 alkyl),
CH.sub.2N(C.sub.1-3 alkyl).sub.2, CH.sub.2CH.sub.2NH.sub.2,
CH.sub.2CH.sub.2NH(C.sub.1-3 alkyl), and
CH.sub.2CH.sub.2N(C.sub.1-3 alkyl).sub.2;
[0026] alternatively, the bridging portion of ring D is absent,
ring E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, and
pyridazinyl, and ring E is substituted with R.sup.a and
R.sup.b;
[0027] R.sup.a is selected from F, Cl, Br, I, OH, OCH.sub.3,
OCH.sub.2CH.sub.3, OCH(CH.sub.3).sub.2, OCH.sub.2CH.sub.2CH.sub.3,
CN, C(.dbd.NR.sup.8)NR.sup.7R.sup.9,
NHC(.dbd.NR.sup.8)NR.sup.7R.sup.9, NR.sup.8CH(.dbd.NR.sup.7),
C(O)NR.sup.7R.sup.8, (CR.sup.8R.sup.9).sub.tNR- .sup.7R.sup.8, SH,
SCH.sub.3, SCH.sub.2CH.sub.3, SCH(CH.sub.3).sub.2,
SCH.sub.2CH.sub.2CH.sub.3, S(O)R.sup.3b, S(O).sub.2R.sup.3a,
S(O).sub.2NR.sup.2R.sup.2a, and OCF.sub.3;
[0028] R.sup.b is selected from H, F, Cl, Br, I, C.sub.1-4 alkyl,
SR.sup.3, CO.sub.2R.sup.3, NO.sub.2, (CH.sub.2).sub.tOR.sup.3,
OCF.sub.3, CF.sub.3, C(O)NR.sup.7R.sup.8, and
(CR.sup.8R.sup.9).sub.tNR.sup.7R.sup.8- ;
[0029] alternatively, R.sup.a and R.sup.b combine to form
methylenedioxy or ethylenedioxy;
[0030] A is selected from:
[0031] C.sub.3-10 carbocycle substituted with 0-2 R.sup.4, and
[0032] 5-10 membered heterocycle consisting of: carbon atoms and
1-4 heteroatoms selected from the group consisting of N, O, and S
substituted with 0-2 R.sup.4;
[0033] B is selected from:
[0034] H, Y, X-Y, C(.dbd.NR.sup.2)NR.sup.2R.sup.2a, and
NR.sup.2C(.dbd.NR.sup.2)NR.sup.2R.sup.2a, provided that Z and B are
attached to different atoms on A;
[0035] X is selected from C.sub.1-4 alkylene,
--CR.sup.2(CR.sup.2R.sup.2b) (CH.sub.2).sub.t--, --C(O)--,
--C(.dbd.NR.sup.1c)--, --CR.sup.2(NR.sup.1cR.sup.2)--,
--CR.sup.2(OR.sup.2)--, --CR.sup.2(SR.sup.2)--,
--C(O)CR.sup.2R.sup.2a--, --CR.sup.2R.sup.2aC(O), --S--, --S(O)--,
--S(O).sub.2--, --SCR.sup.2R.sup.2a--, --S(O)CR.sup.2R.sup.2a--,
--S(O).sub.2CR.sup.2R.sup.2a--, --CR.sup.2R.sup.2aS--,
--CR.sup.2R.sup.2aS(O)--, --CR.sup.2R.sup.2aS (O).sub.2--,
--S(O).sub.2NR.sup.2--, --NR.sup.2S(O).sub.2--,
--NR.sup.2S(O).sub.2CR.sup.2R.sup.2a--, --CR.sup.2R.sup.2aS
(O).sub.2NR.sup.2--, --NR.sup.2S(O).sub.2NR.sup.2--,
--C(O)NR.sup.2--, --NR.sup.2C(O)--,
--C(O)NR.sup.2CR.sup.2R.sup.2a--, --NR.sup.2C(O)CR.sup.2R.sup.2a--,
--CR.sup.2R.sup.2aC(O)NR.sup.2--, --CR.sup.2R.sup.2aNR.sup.2C(O)--,
--NR.sup.2C(O)O--, --OC(O)NR.sup.2--, --NR.sup.2C(O)NR.sup.2--,
--NR.sup.2--, --NR.sup.2CR.sup.2R.sup.2a--,
--CR.sup.2R.sup.2aNR.sup.2--, O, --CR.sup.2R.sup.2aO--, and
--OCR.sup.2R.sup.2a--;
[0036] Y is selected from:
[0037] CH.sub.2NR.sup.2R.sup.2a;
CH.sub.2CH.sub.2NR.sup.2R.sup.2a;
[0038] C.sub.3-10 carbocycle substituted with 0-2 R.sup.4a,
and,
[0039] 5-10 membered heterocycle consisting of: carbon atoms and
1-4 heteroatoms selected from the group consisting of N, O, and S
substituted with 0-2 R.sup.4a;
[0040] R.sup.1a is selected from H, --(CH.sub.2).sub.r--R.sup.1b,
--CH.dbd.CH--R.sup.1b, NCH.sub.2R.sup.1c, OCH.sub.2R.sup.1c,
SCH.sub.2R.sup.1c, NH(CH.sub.2).sub.2(CH.sub.2).sub.tR.sup.1b,
O(CH.sub.2).sub.2(CH.sub.2).sub.tR.sup.1b,
S(CH.sub.2).sub.2(CH.sub.2).su- b.tR.sup.1b,
S(O).sub.p(CH.sub.2).sub.rR.sup.1d, O(CH.sub.2).sub.rR.sup.1d- ,
NR.sup.3(CH.sub.2).sub.rR.sup.1d,
OC(O)NR.sup.3(CH.sub.2).sub.rR.sup.1d,
NR.sup.3C(O)NR.sup.3(CH.sub.2).sub.rR.sup.1d,
NR.sup.3C(O)O(CH.sub.2).sub- .rR.sup.1d, and NR.sup.3C(O)
(CH.sub.2).sub.rR.sup.1d, provided that R.sup.1a forms other than
an N-halo, N--N, N--S, N--O, or N--CN bond;
[0041] R.sup.1b is selected from H, C.sub.1-3 alkyl, F, Cl, Br, I,
--CN, --CHO, (CF.sub.2).sub.rCF.sub.3, (CH.sub.2).sub.rOR.sup.2,
NR.sup.2R.sup.2a, C(O)R.sup.2c, OC(O)R.sup.2,
(CF.sub.2).sub.rCO.sub.2R.s- up.2a, S(O).sub.pR.sup.2b,
NR.sup.2(CH.sub.2).sub.rOR.sup.2,
C(.dbd.NR.sup.2c)NR.sup.2R.sup.2a, NR.sup.2C(O)R.sup.2b,
NR.sup.2C(O)NHR.sup.2b, NR.sup.2C(O).sub.2R.sup.2a,
OC(O)NR.sup.2aR.sup.2b, C(O)NR.sup.2R.sup.2a,
C(O)NR.sup.2(CH.sub.2).sub.- rOR.sup.2, SO.sub.2NR.sup.2R.sup.2a,
NR.sup.2SO.sub.2R.sup.2b, C.sub.3-6 carbocycle substituted with 0-2
R.sup.4a, and 5-10 membered heterocycle consisting of carbon atoms
and from 1-4 heteroatoms selected from the group consisting of N,
O, and S substituted with 0-2 R.sup.4a, provided that R.sup.1b
forms other than an N-halo, N--N, N--S, N--O, or N--CN bond;
[0042] R.sup.1c is selected from H, CH(CH.sub.2OR.sup.2).sub.2,
C(O)R.sup.2c, C(O)NR.sup.2R.sup.2a, S(O)R.sup.2b,
S(O).sub.2R.sup.2b, and SO.sub.2NR.sup.2R.sup.2a;
[0043] R.sup.1d is selected from C.sub.3-6 carbocycle substituted
with 0-2 R.sup.4a, and 5-10 membered heterocycle consisting of
carbon atoms and from 1-4 heteroatoms selected from the group
consisting of N, O, and S substituted with 0-2 R.sup.4a, provided
that R.sup.1d forms other than an N--N, N--S, or N--O bond;
[0044] R.sup.2, at each occurrence, is selected from H, CF.sub.3,
C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocycle substituted with 0-2
R.sup.4b, a C.sub.3-6 carbocyclic-CH.sub.2-residue substituted with
0-2 R.sup.4b, and 5-6 membered heterocycle consisting of: carbon
atoms and 1-4 heteroatoms selected from the group consisting of N,
O, and S substituted with 0-2 R.sup.4b;
[0045] R.sup.2a, at each occurrence, is selected from H, CF.sub.3,
C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocycle substituted with 0-2
R.sup.4b, and 5-6 membered heterocycle consisting of: carbon atoms
and 1-4 heteroatoms selected from the group consisting of N, O, and
S substituted with 0-2 R.sup.4b;
[0046] R.sup.2b, at each occurrence, is selected from CF.sub.3,
C.sub.1-4 alkoxy, C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocycle
substituted with 0-2 R.sup.4b, and 5-6 membered heterocycle
consisting of: carbon atoms and 1-4 heteroatoms selected from the
group consisting of N, O, and S substituted with 0-2 R.sup.4b;
[0047] R.sup.2c, at each occurrence, is selected from CF.sub.3, OH,
C.sub.1-4 alkoxy, C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocyclic
residue substituted with 0-2 R.sup.4b, and 5-6 membered
heterocyclic system containing from 1-4 heteroatoms selected from
the group consisting of N, O, and S substituted with 0-2
R.sup.4b;
[0048] alternatively, R.sup.2 and R.sup.2a, together with the atom
to which they are attached, combine to form a 5 or 6 membered
saturated, partially saturated or unsaturated ring substituted with
0-2 R.sup.4b and consisting of: 0-1 additional heteroatoms selected
from the group consisting of N, O, and S;
[0049] R.sup.3, at each occurrence, is selected from H, C.sub.1-4
alkyl, and phenyl;
[0050] R.sup.3a, at each occurrence, is selected from H, C.sub.1-4
alkyl, benzyl, and phenyl;
[0051] R.sup.3b, at each occurrence, is selected from H, C.sub.1-4
alkyl, and phenyl;
[0052] R.sup.3c, at each occurrence, is selected from C.sub.1-4
alkyl, benzyl, and phenyl;
[0053] R.sup.3d, at each occurrence, is selected from H, C.sub.1-4
alkyl, C.sub.1-4 alkyl-phenyl, and C(.dbd.O)R.sup.3c;
[0054] R.sup.4, at each occurrence, is selected from H, .dbd.O,
(CH.sub.2).sub.rOR.sup.2, F, Cl, Br, I, C.sub.1-4 alkyl, --CN,
NO.sub.2, (CH.sub.2).sub.rNR.sup.2R.sup.2a,
(CH.sub.2).sub.rC(O)R.sup.2c, NR.sup.2C(O)R.sup.2b,
C(O)NR.sup.2R.sup.2a, NR.sup.2C(O)NR.sup.2R.sup.2a,
C(.dbd.NR.sup.2)NR.sup.2R.sup.2a,
C(.dbd.NS(O).sub.2R.sup.5)NR.sup.2R.sup- .2a,
NHC(.dbd.NR.sup.2)NR.sup.2R.sup.2a,
C(O)NHC(.dbd.NR.sup.2)NR.sup.2R.s- up.2a, SO.sub.2NR.sup.2R.sup.2a,
NR.sup.2SO.sub.2NR.sup.2R.sup.2a, NR.sup.2SO.sub.2--C.sub.1-4
alkyl, NR.sup.2SO.sub.2R.sup.5, S(O).sub.pR.sup.5,
(CF.sub.2).sub.rCF.sub.3, NCH.sub.2R.sup.1c, OCH.sub.2R.sup.1c,
SCH.sub.2R.sup.1c, N(CH.sub.2).sub.2(CH.sub.2).sub.tR.- sup.1b,
O(CH.sub.2).sub.2(CH.sub.2).sub.tR.sup.1b, and S(CH.sub.2) 2
(CH.sub.2).sub.tR.sup.1b;
[0055] alternatively, one R.sup.4 is a 5-6 membered aromatic
heterocycle consisting of: carbon atoms and 1-4 heteroatoms
selected from the group consisting of N, O, and S;
[0056] R.sup.4a, at each occurrence, is selected from H, .dbd.O,
(CH.sub.2).sub.rOR.sup.2, (CH.sub.2).sub.r--F,
(CH.sub.2).sub.r--Br, (CH.sub.2).sub.r--Cl, Cl, Br, F, I, C.sub.1-4
alkyl, s-CN, NO.sub.2, (CH.sub.2).sub.rNR.sup.2R.sup.2a,
(CH.sub.2).sub.rC(O)R.sup.2c, NR.sup.2C(O)R.sup.2b,
C(O)NR.sup.2R.sup.2a, (CH.sub.2).sub.rN.dbd.CHOR.su- p.3,
C(O)NH(CH.sub.2).sub.2NR.sup.2R.sup.2a,
NR.sup.2C(O)NR.sup.2R.sup.2a, C(.dbd.NR.sup.2)NR.sup.2R.sup.2a,
NHC(.dbd.NR.sup.2)NR.sup.2R.sup.2a, SO.sub.2NR.sup.2R.sup.2a,
NR.sup.2SO.sub.2NR.sup.2R.sup.2a, NR.sup.2SO.sub.2--C.sub.1-4
alkyl, C(O)NHSO.sub.2--C.sub.1-4 alkyl, NR.sup.2SO.sub.2R.sup.5,
S(O).sub.pR.sup.5, and (CF.sub.2).sub.rCF.sub.3;
[0057] alternatively, one R.sup.4a is phenyl substituted with 0-1
R.sup.5 or a 5-6 membered aromatic heterocycle consisting of:
carbon atoms and 1-4 heteroatoms selected from the group consisting
of N, O, and S substituted with 0-1 R.sup.5;
[0058] R.sup.4b, at each occurrence, is selected from H, .dbd.O,
(CH.sub.2).sub.rOR.sup.3, F, Cl, Br, I, C.sub.1-4 alkyl, --CN,
NO.sub.2, (CH.sub.2).sub.rNR.sup.3R.sup.3a,
(CH.sub.2).sub.rC(O)R.sup.3, (CH.sub.2).sub.rC(O)OR.sup.3c,
NR.sup.3C(O)R.sup.3a, C(O)NR.sup.3R.sup.3a,
NR.sup.3C(O)NR.sup.3R.sup.3a, C(.dbd.NR.sup.3)NR.sup.3R.sup.3a,
NR.sup.3C(.dbd.NR.sup.3)NR.sup.3R.sup.3- a,
SO.sub.2NR.sup.3R.sup.3a, NR.sup.3SO.sub.2NR.sup.3R.sup.3a,
NR.sup.3SO.sub.2--C.sub.1-4 alkyl, NR.sup.3SO.sub.2CF.sub.3,
NR.sup.3SO.sub.2-phenyl, S(O).sub.pCF.sub.3, S(O).sub.p--C.sub.1-4
alkyl, S(O).sub.p-phenyl, and (CF.sub.2).sub.rCF.sub.3;
[0059] R.sup.5, at each occurrence, is selected from H, C.sub.1-6
alkyl, .dbd.O, (CH.sub.2).sub.rOR.sup.3, F, Cl, Br, I, C.sub.1-4
alkyl, --CN, NO.sub.2, (CH.sub.2).sub.rNR.sup.3R.sup.3a,
(CH.sub.2).sub.rC(O)R.sup.3, (CH.sub.2).sub.rC(O)OR.sup.3c,
NR.sup.3C(O)R.sup.3a, C(O)NR.sup.3R.sup.3a,
NR.sup.3C(O)NR.sup.3R.sup.3a, CH(.dbd.NOR.sup.3d),
C(.dbd.NR.sup.3)NR.sup.3R.sup.3a,
NR.sup.3C(.dbd.NR.sup.3)NR.sup.3R.sup.3- a,
SO.sub.2NR.sup.3R.sup.3a, NR.sup.3SO.sub.2NR.sup.3R.sup.3a,
NR.sup.3SO.sub.2--C.sub.1-4 alkyl, NR.sup.3SO.sub.2CF.sub.3,
NR.sup.3SO.sub.2-phenyl, S(O).sub.pCF.sub.3, S(O).sub.p--C.sub.1-4
alkyl, S(O).sub.p-phenyl, (CF.sub.2).sub.rCF.sub.3, phenyl
substituted with 0-2 R.sup.6, naphthyl substituted with 0-2
R.sup.6, and benzyl substituted with 0-2 R.sup.6;
[0060] R.sup.6, at each occurrence, is selected from H, OH,
(CH.sub.2).sub.rOR.sup.2, halo, C.sub.1-4 alkyl, CN, NO.sub.2,
(CH.sub.2).sub.rNR.sup.2R.sup.2a,(CH.sub.2).sub.rC(O)R.sup.2b,
NR.sup.2C(O)R.sup.2b, NR.sup.2C(O)NR.sup.2R.sup.2a,
C(.dbd.NH)NH.sub.2, NHC(.dbd.NH)NH.sub.2, SO.sub.2NR.sup.2R.sup.2a,
NR.sup.2SO.sub.2NR.sup.2R- .sup.2a, and NR.sup.2SO.sub.2C.sub.1-4
alkyl;
[0061] R.sup.7, at each occurrence, is selected from H, OH,
C.sub.1-6 alkyl, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkoxy,
C.sub.1-4 alkoxycarbonyl, (CH.sub.2).sub.n-phenyl, C.sub.6-10
aryloxy, C.sub.6-10 aryloxycarbonyl, C.sub.6-10 arylmethylcarbonyl,
C.sub.1-4 alkylcarbonyloxy C.sub.1-4 alkoxycarbonyl, C.sub.6-10
arylcarbonyloxy C.sub.1-4 alkoxycarbonyl, C.sub.1-6
alkylaminocarbonyl, phenylaminocarbonyl, and phenyl C.sub.1-4
alkoxycarbonyl;
[0062] R.sup.8, at each occurrence, is selected from H, C.sub.1-6
alkyl, and (CH.sub.2).sub.n-phenyl;
[0063] alternatively, R.sup.7 and R.sup.8 combine to form a 5 or 6
membered saturated, ring which contains from 0-1 additional
heteroatoms selected from the group consisting of N, O, and S;
[0064] R.sup.9, at each occurrence, is selected from H, C.sub.1-6
alkyl, and (CH.sub.2) n-phenyl;
[0065] n, at each occurrence, is selected from 0, 1, 2, and 3;
[0066] p, at each occurrence, is selected from 0, 1, and 2;
[0067] r, at each occurrence, is selected from 0, 1, 2, 3, 4, 5,
and 6;
[0068] s, at each occurrence, is selected from 0, 1, and 2;
and,
[0069] t, at each occurrence, is selected from 0, 1, 2, and 3.
[0070] [2] In a preferred embodiment, the present invention
provides a novel compound, wherein:
[0071] G is selected from the group: 891011
[0072] A is selected from one of the following carbocyclic and
heterocyclic systems which are substituted with 0-2 R.sup.4;
[0073] phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl,
furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl,
isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl,
oxadiazolyl, thiadiazolyl, triazolyl, 1,2,3-oxadiazolyl,
1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl,
1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,
1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl,
1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl, benzothiofuranyl,
indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, indazolyl,
benzisoxazolyl, benzisothiazolyl, and isoindazolyl;
[0074] B is Y or X-Y;
[0075] X is selected from C.sub.1-4 alkylene, --C(O)--,
--C(.dbd.NR)--, --CR.sup.2 (NR.sup.2R.sup.2a) -,
--C(O)CR.sup.2R.sup.2a--, --CR.sup.2R.sup.2aC (O),
--C(O)NR.sup.2--, --NR.sup.2C(O)--,
--C(O)NR.sup.2CR.sup.2R.sup.2a--, --NR.sup.2C(O)CR.sup.2R.sup.2a--,
CR.sup.2R.sup.2aC(O)NR.sup.2--, --CR.sup.2R.sup.2aNR.sup.2C(O)--,
--NR.sup.2C(O)NR.sup.2--, --NR.sup.2--,
--NR.sup.2CR.sup.2R.sup.2a--, CR.sup.2R.sup.2aNR.sup.2--, O,
--CR.sup.2R.sup.2aO--, and --OCR.sup.2R.sup.2a;
[0076] Y is CH.sub.2NR.sup.2R.sup.2a or
CH.sub.2CH.sub.2NR.sup.2R.sup.2a;
[0077] alternatively, Y is selected from one of the following
carbocyclic and heterocyclic systems that are substituted with 0-2
R.sup.4a;
[0078] cyclopropyl, cyclopentyl, cyclohexyl, phenyl, piperidinyl,
piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl,
pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, isoxazolinyl,
thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxadiazolyl,
thiadiazolyl, triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl,
1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl,
1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl,
1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl,
benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl,
benzoxazolyl, benzthiazolyl, indazolyl, benzisoxazolyl,
benzisothiazolyl, and isoindazolyl;
[0079] alternatively, Y is selected from the following bicyclic
heteroaryl ring systems: 12
[0080] K is selected from O, S, NH, and N.
[0081] [3] In another preferred embodiment, the present invention
provides a novel compound, wherein:
[0082] G is selected from the group: 1314
[0083] s is 0.
[0084] [4] In another preferred embodiment, the present invention
provides a novel compound, wherein:
[0085] G is selected from: 15
[0086] [5] In another preferred embodiment, the present invention
provides a novel compound, wherein;
[0087] A is selected from phenyl, pyridyl, and pyrimidyl, and is
substituted with 0-2 R.sup.4; and,
[0088] B is selected from phenyl, pyrrolidino,
N-pyrrolidino-carbonyl, morpholino, N-morpholino-carbonyl,
1,2,3-triazolyl, imidazolyl, and benzimidazolyl, and is substituted
with 0-1 R.sup.4a;
[0089] R.sup.2, at each occurrence, is selected from H, CH.sub.3,
CH.sub.2CH.sub.3, cyclopropylmethyl, cyclobutyl, and
cyclopentyl;
[0090] R.sup.2a, at each occurrence, is H or CH.sub.3;
[0091] alternatively, R.sup.2 and R.sup.2a, together with the atom
to which they are attached, combine to form pyrrolidine substituted
with 0-2 R.sup.4b;
[0092] R.sup.4, at each occurrence, is selected from OH,
(CH.sub.2).sub.rOR.sup.2, halo, C.sub.1-4 alkyl,
(CH.sub.2).sub.rNR.sup.2- R.sup.2a, and
(CF.sub.2).sub.rCF.sub.3;
[0093] R.sup.4a is selected from C.sub.1-4 alkyl, CF.sub.3,
(CH.sub.2).sub.rOR.sup.2, (CH.sub.2).sub.rNR.sup.2R.sup.2a,
S(O).sub.pR.sup.5, SO.sub.2NR.sup.2R.sup.2a, and
1-CF.sub.3-tetrazol-2-yl- ;
[0094] R.sup.4b, at each occurrence, is selected from H, CH.sub.3,
and OH;
[0095] R.sup.5, at each occurrence, is selected from CF.sub.3,
C.sub.1-6 alkyl, phenyl, and benzyl; and,
[0096] r, at each occurrence, is selected from 0, 1, and 2.
[0097] [6] In another preferred embodiment, the present invention
provides a novel compound, wherein;
[0098] A is selected from the group: phenyl, 2-pyridyl, 3-pyridyl,
2-pyrimidyl, 2-Cl-phenyl, 3-Cl-phenyl, 2-F-phenyl, 3-F-phenyl,
2-methylphenyl, 2-aminophenyl, and 2-methoxyphenyl; and,
[0099] B is selected from the group: 2-(aminosulfonyl)phenyl,
2-(methylaminosulfonyl)phenyl, 1-pyrrolidinocarbonyl,
2-(methylsulfonyl)phenyl, 2-(N,N-dimethylaminomethyl)phenyl,
2-(N-pyrrolidinylmethyl)phenyl, 1-methyl-2-imidazolyl,
2-methyl-1-imidazolyl, 2-(dimethylaminomethyl)-1-imidazolyl,
2-(N-(cyclopropylmethyl)aminomethyl)phenyl,
2-(N-(cyclobutyl)aminomethyl)- phenyl,
2-(N-(cyclopentyl)aminomethyl)phenyl, and 2-(N-(3-hydroxypyrrolidi-
nyl)methyl)phenyl.
[0100] [7] In another preferred embodiment, the present invention
provides a novel compound selected from:
[0101]
1-(4-methoxyphenyl)-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-7-oxo-6,7-
-dihydro-1H-imidazolo[4,5-c]pyridine;
[0102]
1-(4-methoxyphenyl)-6-{2'-[(methylamino)methyl]-1,1'-biphenyl-4-yl}-
-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0103]
1-(4-methoxyphenyl)-6-{2'-[(dimethylamino)methyl]-1,1'-biphenyl-4-y-
l}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0104]
1-(4-methoxyphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-1,1'-biph-
enyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0105]
1-(4-methoxyphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'-bip-
henyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0106]
1-(4-methoxyphenyl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-biphenyl-4--
yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0107]
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(4-methoxyphen-
yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0108]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0109]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0110]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(4-me-
thoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0111]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(4-methoxyphenyl)-7-o-
xo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0112]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}phenyl)-1-(4-metho-
xyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0113]
1-(4-methoxyphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-7-oxo-6-
,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0114]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-
-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0115]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(4-meth-
oxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0116]
1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-
phenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0117]
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-6-
,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0118]
6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo--
6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0119]
1-(4-methoxyphenyl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0120]
1-(4-methoxyphenyl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-biphe-
nyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0121]
1-(4-methoxyphenyl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-bip-
henyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0122]
1-(4-methoxyphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-fluoro--
1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0123]
1-(4-methoxyphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fluoro-
-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0124]
1-(4-methoxyphenyl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1'-bi-
phenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0125]
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-me-
thoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0126]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0127]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0128]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-1-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0129]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(4-methoxyp-
henyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0130]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)--
1-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0131]
1-(4-methoxyphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-pheny-
l]-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0132]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0133]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)--
1-(4-methoxyphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0134]
1-(4-methoxyphenyl)-6-(4-{(2-[(methylamino)methyl]-1H-imidazol-1-yl-
}-2-fluoro-phenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0135]
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl-
)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0136]
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxypheny-
l)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0137]
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-7-o-
xo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0138]
1-(3-aminomethylphenyl)-6-{2'-[(methylamino)methyl]-1,1'-biphenyl-4-
-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0139]
1-(3-aminomethylphenyl)-6-{(2'-[(dimethylamino)methyl]-1,1'-bipheny-
l-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0140]
1-(3-aminomethylphenyl)-6-{(2'-[(N-ethyl-N-methylamino)methyl]-1,1'-
-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0141]
1-(3-aminomethylphenyl)-6-{(2'-[(N-methyl-N-propylamino)methyl]-1,1-
'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0142]
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-bipheny-
l-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0143]
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminomethyl-
phenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0144]
6-(2'-{([(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)--
1-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0145]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0146]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3-am-
inomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0147]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(3-aminomethylphenyl)-
-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0148]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}phenyl)-1-(3-amino-
methylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0149]
1-(3-aminomethylphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-7-o-
xo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0150]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0151]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-amin-
omethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0152]
1-(3-aminomethylphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-
-yl}phenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0153]
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-7-o-
xo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0154]
6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-7--
oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0155]
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-biphenyl--
4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0156]
1-(3-aminomethylphenyl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-b-
iphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0157]
1-(3-aminomethylphenyl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-
-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0158]
1-(3-aminomethylphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-flu-
oro-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0159]
1-(3-aminomethylphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fl-
uoro-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0160]
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1-
'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0161]
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-am-
inomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0162]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyrid-
ine;
[0163]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyrid-
ine;
[0164]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-1-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0165]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(3-aminomet-
hylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0166]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)--
1-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0167]
1-(3-aminomethylphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-p-
henyl]-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0168]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyrid-
ine;
[0169]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)--
1-(3-aminomethylphenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0170]
1-(3-aminomethylphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-
-yl}-2-fluoro-phenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0171]
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylph-
enyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0172]
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylp-
henyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0173]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-y-
l}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0174]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(methylamino)methyl]-1,1'-biph-
enyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0175]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(dimethylamino)methyl]-1,1'-bi-
phenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0176]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-
-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0177]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamino)methyl-
]-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0178]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-b-
iphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c] pyridine;
[0179]
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminobenzis-
oxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0180]
6-(2'{[-(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine-
;
[0181]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine-
;
[0182]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3-am-
inobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0183]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl)-1-(3-aminobenzisoxazol--
5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0184]
6-(4-{(2-[(dimethylamino)methyl]-1H-imidazol-1-yl.gamma.phenyl)-1-(-
3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0185]
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(2-methyl-1H-imidazol-1-yl)pheny-
l]-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0186]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine-
;
[0187]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-amin-
obenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0188]
1-(3-aminobenzisoxazol-5'-yl)-6-(4-{2-[(methylamino)methyl]-1H-imid-
azol-1-yl}phenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0189]
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5'-y-
l)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0190]
6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5'--
yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0191]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-bip-
henyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0192]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(methylamino)methyl]-3-fluoro--
1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0193]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(dimethylamino)methyl]-3-fluor-
o-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0194]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-
-3-fluoro-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridin-
e;
[0195]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamino)methyl-
]-3-fluoro-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridi-
ne;
[0196]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-3-fluo-
ro-1,1'-biphenyl-4-yl}-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0197]
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-am-
inobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0198]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c-
]pyridine;
[0199]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c-
]pyridine;
[0200]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyrid-
ine;
[0201]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(3-aminoben-
zisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0202]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)--
1-(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridin-
e;
[0203]
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fl-
uoro-phenyl]-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0204]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c-
]pyridine;
[0205]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)--
1-(3-aminobenzisoxazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridin-
e;
[0206]
1-(3-aminobenzisoxazol-5'-yl)-6-(4-{2-[(methylamino)methyl]-1H-imid-
azol-1-yl}-2-fluoro-phenyl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0207]
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminobenzisox-
azol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0208]
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminobenziso-
xazol-5'-yl)-7-oxo-6,7-dihydro-1H-imidazolo[4,5-c]pyridine;
[0209]
3-[6,7-dihydro-6-[2'-[aminomethyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-im-
idazolo[4,5-c]pyridin-1-yl]benzamide;
[0210]
3-[6,7-dihydro-6-[2'-[[methylamino]methyl][1,1'-biphenyl]-4-yl]-7-o-
xo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0211]
3-[6,7-dihydro-6-[2'-[[dimethylamino]methyl][1,1'-biphenyl]-4-yl]-7-
-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0212]
3-[6,7-dihydro-6-[2'-[[4-hydroxypiperidin-1-yl]methyl][1,1'-bipheny-
l]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0213]
3-[6,7-dihydro-6-[2'-[[N-ethyl-N-methylamino]methyl][1,1'-biphenyl]-
-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0214]
3-[6,7-dihydro-6-[2'-[[pyrrolidin-1-yl]methyl][1,1'-biphenyl]-4-yl]-
-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0215]
3-[6,7-dihydro-6-[2'-[[3(R)-hydroxypyrrolidin-1-yl]methyl][1,1'-bip-
henyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0216]
3-[6,7-dihydro-6-[2'-[[3(S)-hydroxypyrrolidin-1-yl]methyl][1,1'-bip-
henyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0217]
3-[6,7-dihydro-6-[2'-[[N-propyl-N-methylamino]methyl][1,1'-biphenyl-
]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0218]
3-[6,7-dihydro-6-[2'-[[t-butylamino]methyl][1,1'-biphenyl]-4-yl]-7--
oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0219]
3-[6,7-dihydro-6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-7-oxo-1H-
-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0220]
3-[6,7-dihydro-6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}phe-
nyl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0221]
3-[6,7-dihydro-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-7-oxo-1H-imi-
dazolo[4,5-c]pyridin-1-yl]benzamide;
[0222]
3-[6,7-dihydro-6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-b-
iphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0223]
3-[6,7-dihydro-6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl--
4-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0224]
3-[6,7-dihydro-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}pheny-
l)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0225]
3-[6,7-dihydro-6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-7-oxo-1H-imi-
dazolo[4,5-c]pyridin-1-yl]benzamide;
[0226]
3-[6,7-dihydro-6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-7-oxo-1H-im-
idazolo[4,5-c]pyridin-1-yl]benzamide;
[0227]
3-[6,7-dihydro-6-[2'-[aminomethyl]-3-fluoro-[1,1'-biphenyl]-4-yl]-7-
-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0228]
3-[6,7-dihydro-6-[2'-[[methylamino]methyl]-3-fluoro-[1,1'-biphenyl]-
-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0229]
3-[6,7-dihydro-6-[2'-[[dimethylamino]methyl]-3-fluoro-[1,1'-bipheny-
l]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0230]
3-[6,7-dihydro-6-[2'-[[4-hydroxypiperidin-1-yl]methyl]-3-fluoro-[1,-
1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0231]
3-[6,7-dihydro-6-[2'-[[N-ethyl-N-methylamino]methyl]-3-fluoro-[1,1'-
-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0232]
3-[6,7-dihydro-6-[2'-[[pyrrolidin-1-yl]methyl]-3-fluoro-[1,1'-biphe-
nyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0233]
3-[6,7-dihydro-6-[2'-[[3(R)-hydroxypyrrolidin-1-yl]methyl]-3-fluoro-
-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0234]
3-[6,7-dihydro-6-[2'-[[3(S)-hydroxypyrrolidin-1-yl]methyl]-3-fluoro-
-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0235]
3-[6,7-dihydro-6-[2'-[[N-propyl-N-methylamino]methyl]-3-fluoro-[1,1-
'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0236]
3-[6,7-dihydro-6-[2'-[[t-butylamino]methyl]-3-fluoro-[1,1'-biphenyl-
]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0237]
3-[6,7-dihydro-6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl-
}-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0238]
3-[6,7-dihydro-6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2--
fluoro-phenyl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0239]
3-[6,7-dihydro-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-phenyl]-7--
oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0240]
3-[6,7-dihydro-6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluo-
ro-1,1'-biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0241]
3-[6,7-dihydro-6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'--
biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0242]
3-[6,7-dihydro-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-2-fl-
uoro-phenyl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0243]
3-[6,7-dihydro-6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-7-o-
xo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide; and,
[0244]
3-[6,7-dihydro-6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-7--
oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0245] or a pharmaceutically acceptable salt form thereof.
[0246] [8] In another embodiment, the present invention provides a
novel compound of formula III: 16
[0247] or a stereoisomer or pharmaceutically acceptable salt
thereof, wherein;
[0248] ring M, including M.sub.1 and M.sub.2, is a 6 or 7 membered
carbocycle or 6 or 7 membered heterocycle, consisting of: carbon
atoms, and 1-3 heteroatoms selected from O, S(O).sub.p, N, and
N--Z.sup.2;
[0249] provided that ring M is other than: 17
[0250] ring M is substituted with 0-2 R.sup.3 and 0-2 carbonyl
groups, and, comprises: 0-2 double bonds;
[0251] alternatively, M.sub.1 is C(O), M.sub.2 is N, and the
remainder of ring M is S(O).sub.2;
[0252] M.sub.3 is -A-B;
[0253] G is a group of formula IIa or IIb: 18
[0254] ring D, including the two atoms of Ring E to which it is
attached, is a 5-6 membered non-aromatic ring consisting of carbon
atoms, 0-1 double bonds, and from 0-2 N, and D is substituted with
0-2 R, provided that when ring D is unsubstituted, it contains at
least one heteroatom;
[0255] alternatively, ring D, including the two atoms of Ring E to
which it is attached, is a 5-6 membered aromatic system consisting
of carbon atoms and from 0-2 heteroatoms selected from the group
consisting of N, O, and S, and D is substituted with 0-2 R,
provided that when ring D is unsubstituted, it contains at least
one heteroatom;
[0256] E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl,
and pyridazinyl, and is substituted with 0-1 R;
[0257] R is selected from F, Cl, Br, I, OH, OCH.sub.3,
OCH.sub.2CH.sub.3, OCH(CH.sub.3).sub.2, OCH.sub.2CH.sub.2CH.sub.3,
NH.sub.2, NH(C.sub.1-3 alkyl), N(C.sub.1-3 alkyl).sub.2,
C(.dbd.NH)NH.sub.2, CH.sub.2NH.sub.2, CH.sub.2NH(C.sub.1-3 alkyl),
CH.sub.2N(C.sub.1-3 alkyl).sub.2, CH.sub.2CH.sub.2NH.sub.2,
CH.sub.2CH.sub.2NH(C.sub.1-3 alkyl), and
CH.sub.2CH.sub.2N(C.sub.1-3 alkyl).sub.2;
[0258] alternatively, the bridging portion of ring D is absent,
ring E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, and
pyridazinyl, and ring E is substituted with R.sup.a and
R.sup.b;
[0259] R.sup.a is selected from F, Cl, Br, I, OH, OCH.sub.3,
OCH.sub.2CH.sub.3, OCH(CH.sub.3) 2, OCH.sub.2CH.sub.2CH.sub.3, CN,
C(.dbd.NR.sup.8)NR.sup.7R.sup.9, NHC(.dbd.NR.sup.8)NR.sup.7R.sup.9,
NR.sup.8CH(.dbd.NR.sup.7), C(O)NR.sup.7R.sup.8,
(CR.sup.8R.sup.9).sub.tNR- .sup.7R.sup.8, SH, SCH.sub.3,
SCH.sub.2CH.sub.3, SCH(CH.sub.3).sub.2, SCH.sub.2CH.sub.2CH.sub.3,
S(O)R.sup.3b, S(O).sub.2R.sup.3a, S(O).sub.2NR.sup.2R.sup.2a, and
OCF.sub.3;
[0260] R.sup.b is selected from H, F, Cl, Br, I, C.sub.1-4 alkyl,
SR.sup.3, CO.sub.2R.sup.3, NO.sub.2, (CH.sub.2).sub.tOR.sup.3,
OCF.sub.3, CF.sub.3, C(O)NR.sup.7R.sup.8, and
(CR.sup.8R.sup.9).sub.tNR.sup.7R.sup.8- ;
[0261] alternatively, R.sup.a and R.sup.b combine to form
methylenedioxy or ethylenedioxy;
[0262] A is selected from:
[0263] C.sub.3-10 carbocycle substituted with 0-2 R.sup.4, and
[0264] 5-10 membered heterocycle consisting of: carbon atoms and
1-4 heteroatoms selected from the group consisting of N, O, and S
substituted with 0-2 R.sup.4;
[0265] B is selected from:
[0266] H, Y, X-Y, C(.dbd.NR.sup.2)NR.sup.2R.sup.2a, and
NR.sup.2C(.dbd.NR.sup.2)NR.sup.2R.sup.2a, provided that Z and B are
attached to different atoms on A;
[0267] X is selected from C.sub.1-4 alkylene,
--CR.sup.2(CR.sup.2R.sup.2b) (CH.sub.2).sub.t--, --C(O)--,
--C(.dbd.NR.sup.1c)--, --CR.sup.2(NR.sup.1cR.sup.2)--,
--CR.sup.2(OR.sup.2)--, --CR.sup.2(SR.sup.2)--,
C(O)CR.sup.2R.sup.2a--, --CR.sup.2R.sup.2aC(O), --S--, --S(O)--,
--S(O).sub.2--, --SCR.sup.2R.sup.2a--, --S(O)CR.sup.2R.sup.2a--,
--S(O).sub.2CR.sup.2R.sup.2a--, --CR.sup.2R.sup.2aS--,
--CR.sup.2R.sup.2aS(O)--, --CR.sup.2R.sup.2aS(O).s- ub.2--,
--S(O).sub.2NR.sup.2--, --NR.sup.2S(O).sub.2--,
--NR.sup.2S(O).sub.2CR.sup.2R.sup.2a--, --CR.sup.2R.sup.2aS
(O).sub.2NR.sup.2--, --NR.sup.2S(O).sub.2NR.sup.2--,
--C(O)NR.sup.2--, --NR.sup.2C(O)--,
--C(O)NR.sup.2CR.sup.2R.sup.2a--, --NR.sup.2C(O)CR.sup.2R.sup.2a--,
--CR.sup.2R.sup.2aC(O)NR.sup.2--, --CR.sup.2R.sup.2aNR.sup.2C(O)--,
--NR.sup.2C(O)O--, --OC(O)NR.sup.2--, --NR.sup.2C(O)NR.sup.2--,
--NR.sup.2--, --NR.sup.2CR.sup.2R.sup.2a--,
--CR.sup.2R.sup.2aNR.sup.2--, O, --CR.sup.2R.sup.2aO--, and
--OCR.sup.2R.sup.2a--;
[0268] Y is selected from:
[0269] CH.sub.2NR.sup.2R.sup.2a;
CH.sub.2CH.sub.2NR.sup.2R.sup.2a;
[0270] C.sub.3-10 carbocycle substituted with 0-2 R.sup.4a,
and,
[0271] 5-10 membered heterocycle consisting of: carbon atoms and
1-4 heteroatoms selected from the group consisting of N, O, and S
substituted with 0-2 R.sup.4a;
[0272] Z.sup.2 is selected from H, C.sub.1-4 alkyl, phenyl, benzyl,
C(O)R.sup.3, and S(O).sub.pR.sup.3c;
[0273] R.sup.1a is selected from H, --(CH.sub.2).sub.r-R.sup.b,
--CH.dbd.CH--R.sup.1b, NCH.sub.2R.sup.1c, OCH.sub.2R.sup.1c,
SCH.sub.2R.sup.1c, NH(CH.sub.2).sub.2(CH.sub.2).sub.tR.sup.1b,
O(CH.sub.2).sub.2(CH.sub.2).sub.tR.sup.1b,
S(CH.sub.2).sub.2(CH.sub.2).su- b.tR.sup.1b,
S(O).sub.p(CH.sub.2).sub.rR.sup.1d, O(CH.sub.2).sub.rR d,
NR.sup.3(CH.sub.2).sub.rR.sup.1d, OC(O)NR.sup.3
(CH.sub.2).sub.rR.sup.1d, NR.sup.3C(O)NR.sup.3
(CH.sub.2).sub.rR.sup.1d, NR.sup.3cC(O)O (CH.sub.2).sub.rR.sup.1d,
and NR.sup.3C(O) (CH.sub.2).sub.rR.sup.1d, provided that R.sup.1a
forms other than an N-halo, N--N, N--S, N--O, or N--CN bond;
[0274] R.sup.1b is selected from H, C.sub.1-3 alkyl, F, Cl, Br, I,
--CN, --CHO, (CF.sub.2).sub.rCF.sub.3, (CH.sub.2).sub.rOR.sup.2,
NR.sup.2R.sup.2a, C(O)R.sup.2c, OC(O)R.sup.2,
(CF.sub.2).sub.rCO.sub.2R.s- up.2a, S(O).sub.pR.sup.2b,
NR.sup.2(CH.sub.2).sub.rOR.sup.2,
C(.dbd.NR.sup.2c)NR.sup.2R.sup.2a, NR.sup.2C(O)R.sup.2b,
NR.sup.2C(O)NHR.sup.2b, NR.sup.2C(O).sub.2R.sup.2a,
OC(O)NR.sup.2aR.sup.2b, C(O)NR.sup.2R.sup.2a,
C(O)NR.sup.2(CH.sub.2).sub.- rOR.sup.2, SO.sub.2NR.sup.2R.sup.2a,
NR.sup.2SO.sub.2R.sup.2b, C.sub.3-6 carbocycle substituted with 0-2
R.sup.4a, and 5-10 membered heterocycle consisting of carbon atoms
and from 1-4 heteroatoms selected from the group consisting of N,
O, and S substituted with 0-2 R.sup.4a, provided that R.sup.1b
forms other than an N-halo, N--N, N--S, N--O, or N--CN bond;
[0275] R.sup.1c is selected from H, CH(CH.sub.2OR.sup.2).sub.2,
C(O)R.sup.2c, C(O)NR.sup.2R.sup.2a, S(O)R.sup.2b,
S(O).sub.2R.sup.2b, and SO.sub.2NR.sup.2R.sup.2a;
[0276] R.sup.1d is selected from C.sub.3-6 carbocycle substituted
with 0-2 R.sup.4a, and 5-10 membered heterocycle consisting of
carbon atoms and from 1-4 heteroatoms selected from the group
consisting of N, O, and S substituted with 0-2 R.sup.4a, provided
that R.sup.1d forms other than an N--N, N--S, or N--O bond;
[0277] R.sup.2, at each occurrence, is selected from H, CF.sub.3,
C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocycle substituted with 0-2
R.sup.4b, a C.sub.3-6 carbocyclic-CH.sub.2-residue substituted with
0-2 R.sup.4b, and 5-6 membered heterocycle consisting of: carbon
atoms and 1-4 heteroatoms selected from the group consisting of N,
O, and S substituted with 0-2 R.sup.4b;
[0278] R.sup.2a, at each occurrence, is selected from H, CF.sub.3,
C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocycle substituted with 0-2
R.sup.4b, and 5-6 membered heterocycle consisting of: carbon atoms
and 1-4 heteroatoms selected from the group consisting of N, O, and
S substituted with 0-2 R.sup.4b;
[0279] R.sup.2b, at each occurrence, is selected from CF.sub.3,
C.sub.1-4 alkoxy, C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocycle
substituted with 0-2 R.sup.4b, and 5-6 membered heterocycle
consisting of: carbon atoms and 1-4 heteroatoms selected from the
group consisting of N, O, and S substituted with 0-2 R.sup.4b;
[0280] R.sup.2c, at each occurrence, is selected from CF.sub.3, OH,
C.sub.1-4 alkoxy, C.sub.1-6 alkyl, benzyl, C.sub.3-6 carbocyclic
residue substituted with 0-2 R.sup.4b, and 5-6 membered
heterocyclic system containing from 1-4 heteroatoms selected from
the group consisting of N, O, and S substituted with 0-2
R.sup.4b;
[0281] alternatively, R.sup.2 and R.sup.2a, together with the atom
to which they are attached, combine to form a 5 or 6 membered
saturated, partially saturated or unsaturated ring substituted with
0-2 R.sup.4b and consisting of: 0-1 additional heteroatoms selected
from the group consisting of N, O, and S;
[0282] R.sup.3, at each occurrence, is selected from H, C.sub.1-4
alkyl, and phenyl;
[0283] R.sup.3a, at each occurrence, is selected from H, C.sub.1-4
alkyl, benzyl, and phenyl;
[0284] R.sup.3b, at each occurrence, is selected from H, C.sub.1-4
alkyl, and phenyl;
[0285] R.sup.3c, at each occurrence, is selected from C.sub.1-4
alkyl, benzyl, and phenyl;
[0286] R.sup.3d, at each occurrence, is selected from H, C.sub.1-4
alkyl, C.sub.1-4 alkyl-phenyl, and C(.dbd.O)R.sup.3c;
[0287] R.sup.4, at each occurrence, is selected from H, .dbd.O,
(CH.sub.2).sub.rOR.sup.2, F, Cl, Br, I, C.sub.1-4 alkyl, --CN,
NO.sub.2, (CH.sub.2).sub.rNR.sup.2R.sup.2a,
(CH.sub.2).sub.rC(O)R.sup.2c, NR.sup.2C(O)R.sup.2b,
C(O)NR.sup.2R.sup.2a, NR.sup.2C(O)NR.sup.2R.sup.2a,
C(.dbd.NR.sup.2)NR.sup.2R.sup.2a,
C(.dbd.NS(O).sub.2R.sup.5)NR.sup.2R.sup- .2a,
NHC(.dbd.NR.sup.2)NR.sup.2R.sup.2a, C(O)NHC
(.dbd.NR.sup.2)NR.sup.2R.- sup.2a, SO.sub.2NR.sup.2R.sup.2a,
NR.sup.2SO.sub.2NR.sup.2R.sup.2a, NR.sup.2SO.sub.2--C.sub.1-4
alkyl, NR.sup.2SO.sub.2R.sup.5, S(O).sub.pR.sup.5,
(CF.sub.2).sub.rCF.sub.3, NCH.sub.2R.sup.1c, OCH.sub.2R.sup.1c,
SCH.sub.2R.sup.1c, N(CH.sub.2).sub.2(CH.sub.2).sub.tR.- sup.1b,
O(CH.sub.2).sub.2(CH.sub.2).sub.tR.sup.1b, and
S(CH.sub.2).sub.2(CH.sub.2).sub.tR.sup.1b;
[0288] alternatively, one R.sup.4 is a 5-6 membered aromatic
heterocycle consisting of: carbon atoms and 1-4 heteroatoms
selected from the group consisting of N, O, and S;
[0289] R.sup.4a, at each occurrence, is selected from H, .dbd.O,
(CH.sub.2).sub.rOR.sup.2, (CH.sub.2).sub.r--F,
(CH.sub.2).sub.r--Br, (CH.sub.2).sub.r--Cl, Cl, Br, F, I, C.sub.1-4
alkyl, s-CN, NO.sub.2, (CH.sub.2).sub.rNR.sup.2R.sup.2a,
(CH.sub.2).sub.rC(O)R.sup.2c, NR.sup.2C(O)R.sup.2b,
C(O)NR.sup.2R.sup.2a, (CH.sub.2).sub.rN.dbd.CHOR.su- p.3,
C(O)NH(CH.sub.2).sub.2NR.sup.2R.sup.2a,
NR.sup.2C(O)NR.sup.2R.sup.2a, C(.dbd.NR.sup.2)NR.sup.2R.sup.2a,
NHC(.dbd.NR.sup.2)NR.sup.2R.sup.2a, SO.sub.2NR.sup.2R.sup.2a,
NR.sup.2SO.sub.2NR.sup.2R.sup.2a, NR.sup.2SO.sub.2--C.sub.1-4
alkyl, C(O)NHSO.sub.2--C.sub.1-4 alkyl, NR.sup.2SO.sub.2R.sup.5,
S(O).sub.pR.sup.5, and (CF.sub.2).sub.rCF.sub.3;
[0290] alternatively, one R.sup.4a is phenyl substituted with 0-1
R.sup.5 or a 5-6 membered aromatic heterocycle consisting of:
carbon atoms and 1-4 heteroatoms selected from the group consisting
of N, O, and S substituted with 0-1 R.sup.5;
[0291] R.sup.4b, at each occurrence, is selected from H, .dbd.O,
(CH.sub.2).sub.rOR.sup.3, F, Cl, Br, I, C.sub.1-4 alkyl, --CN,
NO.sub.2, (CH.sub.2).sub.rNR.sup.3R.sup.3a,
(CH.sub.2).sub.rC(O)R.sup.3, (CH.sub.2).sub.rC(O)OR.sup.3c,
NR.sup.3C(O)R.sup.3a, C(O)NR.sup.3R.sup.3a,
NR.sup.3C(O)NR.sup.3R.sup.3a, C(.dbd.NR.sup.3)NR.sup.3R.sup.3a,
NR.sup.3C(.dbd.NR.sup.3)NR.sup.3R.sup.3- a,
SO.sub.2NR.sup.3R.sup.3a, NR.sup.3SO.sub.2NR.sup.3R.sup.3a,
NR.sup.3SO.sub.2--C.sub.1-4 alkyl, NR.sup.3SO.sub.2CF.sub.3,
NR.sup.3SO.sub.2-phenyl, S(O).sub.pCF.sub.3, S(O).sub.p--C.sub.1-4
alkyl, S(O).sub.p-phenyl, and (CF.sub.2).sub.rCF.sub.3;
[0292] R.sup.5, at each occurrence, is selected from H, C.sub.1-6
alkyl, .dbd.O, (CH.sub.2).sub.rOR.sup.3, F, Cl, Br, I, C.sub.1-4
alkyl, --CN, NO.sub.2, (CH.sub.2).sub.rNR.sup.3R.sup.3a,
(CH.sub.2).sub.rC(O)R.sup.3, (CH.sub.2).sub.rC(O)OR.sup.3c,
NR.sup.3C(O)R.sup.3a, C(O)NR.sup.3R.sup.3a,
NR.sup.3C(O)NR.sup.3R.sup.3a, CH(.dbd.NOR.sup.3d),
C(.dbd.NR.sup.3)NR.sup.3R.sup.3a,
NR.sup.3C(.dbd.NR.sup.3)NR.sup.3R.sup.3- a,
SO.sub.2NR.sup.3R.sup.3a, NR.sup.3SO.sub.2NR.sup.3R.sup.3a,
NR.sup.3SO.sub.2--C.sub.1-4 alkyl, NR.sup.3SO.sub.2CF.sub.3,
NR.sup.3SO.sub.2-phenyl, S(O).sub.pCF.sub.3, S(O).sub.p--C.sub.1-4
alkyl, S(O).sub.p-phenyl, (CF.sub.2).sub.rCF.sub.3, phenyl
substituted with 0-2 R.sup.6, naphthyl substituted with 0-2
R.sup.6, and benzyl substituted with 0-2 R.sup.6;
[0293] R.sup.6, at each occurrence, is selected from H, OH,
(CH.sub.2).sub.rOR.sup.2, halo, C.sub.1-4 alkyl, CN, NO.sub.2,
(CH.sub.2).sub.rNR.sup.2R.sup.2a, (CH.sub.2).sub.rC(O)R.sup.2b,
NR.sup.2C(O)R.sup.2b, NR.sup.2C(O)NR.sup.2R.sup.2a,
C(.dbd.NH)NH.sub.2, NHC (.dbd.NH)NH.sub.2,
SO.sub.2NR.sup.2R.sup.2a, NR.sup.2SO.sub.2NR.sup.2- R.sup.2a, and
NR.sup.2SO.sub.2C.sub.1-4 alkyl;
[0294] R.sup.7, at each occurrence, is selected from H, OH,
C.sub.1-6 alkyl, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkoxy,
C.sub.1-4 alkoxycarbonyl, (CH.sub.2).sub.n-phenyl, C.sub.6-10
aryloxy, C.sub.6-10 aryloxycarbonyl, C.sub.6-10 arylmethylcarbonyl,
C.sub.1-4 alkylcarbonyloxy C.sub.1-4 alkoxycarbonyl, C.sub.6-10
arylcarbonyloxy C.sub.1-4 alkoxycarbonyl, C.sub.1-6
alkylaminocarbonyl, phenylaminocarbonyl, and phenyl C.sub.1-4
alkoxycarbonyl;
[0295] R.sup.8, at each occurrence, is selected from H, C.sub.1-6
alkyl, and (CH.sub.2) n-phenyl;
[0296] alternatively, R.sup.7 and R.sup.8 combine to form a 5 or 6
membered saturated, ring which contains from 0-1 additional
heteroatoms selected from the group consisting of N, O, and S;
[0297] R.sup.9, at each occurrence, is selected from H, C.sub.1-6
alkyl, and (CH.sub.2).sub.n-phenyl;
[0298] n, at each occurrence, is selected from 0, 1, 2, and 3;
[0299] p, at each occurrence, is selected from 0, 1, and 2;
[0300] r, at each occurrence, is selected from 0, 1, 2, 3, 4, 5,
and 6;
[0301] s, at each occurrence, is selected from 0, 1, and 2;
and,
[0302] t, at each occurrence, is selected from 0, 1, 2, and 3.
[0303] [9] In another preferred embodiment, the present invention
provides a novel compound, wherein:
[0304] ring M is substituted with 0-2 R.sup.3 and is selected from
the group: 1920
[0305] Z.sup.2 is selected from H, C.sub.1-4 alkyl, phenyl, benzyl,
C(O)R.sup.3, and S(O).sub.pR.sup.3c;
[0306] G is selected from the group: 21222324
[0307] A is selected from one of the following carbocyclic and
heterocyclic systems which are substituted with 0-2 R.sup.4;
[0308] phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl,
furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl,
isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl,
oxadiazolyl, thiadiazolyl, triazolyl, 1,2,3-oxadiazolyl,
1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl,
1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,
1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl,
1,2,5-triazolyl, 1,3,4-triazolyl, benzofuranyl, benzothiofuranyl,
indolyl, benzimidazolyl, benzoxazolyl, benzthiazolyl, indazolyl,
benzisoxazolyl, benzisothiazolyl, and isoindazolyl;
[0309] B is Y or X-Y;
[0310] X is selected from C.sub.1-4 alkylene, --C(O)--,
--C(.dbd.NR)--, --CR.sup.2 (NR.sup.2R.sup.2a)--,
--C(O)CR.sup.2R.sup.2a--, --CR.sup.2R.sup.2aC (O),
--C(O)NR.sup.2--, --NR.sup.2C(O)--,
--C(O)NR.sup.2CR.sup.2R.sup.2a--, --NR.sup.2C(O)CR.sup.2R.sup.2a--,
--CR.sup.2R.sup.2aC(O)NR.sup.2--, --CR.sup.2R.sup.2aNR.sup.2C(O)--,
--NR.sup.2C(O)NR.sup.2--, --NR.sup.2--, --NR.sup.2CR.sup.2R.sup.2a
--, --CR.sup.2R.sup.2aNR.sup.2--, O, --CR.sup.2R.sup.2aO--, and
--OCR.sup.2R.sup.2a--;
[0311] Y is CH.sub.2NR.sup.2R.sup.2a or
CH.sub.2CH.sub.2NR.sup.2R.sup.2a;
[0312] alternatively, Y is selected from one of the following
carbocyclic and heterocyclic systems that are substituted with 0-2
R.sup.4a;
[0313] cyclopropyl, cyclopentyl, cyclohexyl, phenyl, piperidinyl,
piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl,
pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, isoxazolinyl,
thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxadiazolyl,
thiadiazolyl, triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl,
1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl,
1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl,
1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl,
benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl,
benzoxazolyl, benzthiazolyl, indazolyl, benzisoxazolyl,
benzisothiazolyl, and isoindazolyl;
[0314] alternatively, Y is selected from the following bicyclic
heteroaryl ring systems: 25
[0315] K is selected from O, S, NH, and N.
[0316] [10] In another preferred embodiment, the present invention
provides a novel compound, wherein:
[0317] ring M is substituted with 0-2 R.sup.3 and is selected from
the group: 2627
[0318] G is selected from the group: 2829
[0319] [11] In another preferred embodiment, the present invention
provides a novel compound, wherein:
[0320] ring M is substituted with 0-1 R.sup.3 and is selected from
the group: 30
[0321] G is selected from: 31
[0322] [12] In another preferred embodiment, the present invention
provides a novel compound, wherein;
[0323] A is selected from phenyl, pyridyl, and pyrimidyl, and is
substituted with 0-2 R.sup.4; and,
[0324] B is selected from phenyl, pyrrolidino,
N-pyrrolidino-carbonyl, morpholino, N-morpholino-carbonyl,
1,2,3-triazolyl, imidazolyl, and benzimidazolyl, and is substituted
with 0-1 R.sup.4a;
[0325] R.sup.2, at each occurrence, is selected from H, CH.sub.3,
CH.sub.2CH.sub.3, cyclopropylmethyl, cyclobutyl, and
cyclopentyl;
[0326] R.sup.2a, at each occurrence, is H or CH.sub.3;
[0327] alternatively, R.sup.2 and R.sup.2a, together with the atom
to which they are attached, combine to form pyrrolidine substituted
with 0-2 R.sup.4b;
[0328] R.sup.4, at each occurrence, is selected from OH,
(CH.sub.2).sub.rOR.sup.2, halo, C.sub.1-4 alkyl,
(CH.sub.2).sub.rNR.sup.2- R.sup.2a, and
(CF.sub.2).sub.rCF.sub.3;
[0329] R.sup.4a is selected from C.sub.1-4 alkyl, CF.sub.3,
(CH.sub.2).sub.rOR.sup.2, (CH.sub.2).sub.rNR.sup.2R.sup.2a,
S(O).sub.pR.sup.5, SO.sub.2NR.sup.2R.sup.2a, and
1-CF.sub.3-tetrazol-2-yl- ;
[0330] R.sup.4b, at each occurrence, is selected from H, CH.sub.3,
and OH;
[0331] R.sup.5, at each occurrence, is selected from CF.sub.3,
C.sub.1-6 alkyl, phenyl, and benzyl; and,
[0332] r, at each occurrence, is selected from 0, 1, and 2.
[0333] [13] In another embodiment, the present invention provides a
novel compound, wherein;
[0334] A is selected from the group: phenyl, 2-pyridyl, 3-pyridyl,
2-pyrimidyl, 2-Cl-phenyl, 3-Cl-phenyl, 2-F-phenyl, 3-F-phenyl,
2-methylphenyl, 2-aminophenyl, and 2-methoxyphenyl; and,
[0335] B is selected from the group: 2-(aminosulfonyl)phenyl,
2-(methylaminosulfonyl)phenyl, 1-pyrrolidinocarbonyl,
2-(methylsulfonyl)phenyl, 2-(N,N-dimethylaminomethyl) phenyl,
2-(N-pyrrolidinylmethyl)phenyl, 1-methyl-2-imidazolyl,
2-methyl-1-imidazolyl, 2-(dimethylaminomethyl)-1-imidazolyl,
2-(N-(cyclopropylmethyl)aminomethyl)phenyl,
2-(N-(cyclobutyl)aminomethyl)- phenyl,
2-(cyclopentyl)aminomethyl)phenyl, and 2-(N-(3-hydroxypyrrolidinyl-
)methyl)phenyl.
[0336] [14] In another preferred embodiment, the present invention
provides a novel compound selected from:
[0337]
7-(3-aminomethyl-phenyl)-1-(2'-methanesulfonyl-biphenyl-4-yl)-3-pro-
pyl-3,7-dihydro-purine-2,6 dione;
[0338]
1-(4-methoxyphenyl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-7-oxo-4-
,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0339]
1-(4-methoxyphenyl)-6-{2'-[(methylamino)methyl]-1,1'-biphenyl-4-yl}-
-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0340]
1-(4-methoxyphenyl)-6-{2'-[(dimethylamino)methyl]-1,1'-biphenyl-4-y-
l}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0341]
1-(4-methoxyphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-1,1'-biph-
enyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0342]
1-(4-methoxyphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'-bip-
henyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0343]
1-(4-methoxyphenyl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-biphenyl-4--
yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0344]
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(4-methoxyphen-
yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0345]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0346]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0347]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(4-me-
thoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0348]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(4-methoxyphenyl)-7-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0349]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}phenyl)-1-(4-metho-
xyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0350]
1-(4-methoxyphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-7-oxo-4-
,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0351]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-
-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0352]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(4-meth-
oxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0353]
1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-
phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0354]
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-4-
,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0355]
6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo--
4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0356]
1-(4-methoxyphenyl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0357]
1-(4-methoxyphenyl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-biphe-
nyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0358]
1-(4-methoxyphenyl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-bip-
henyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0359]
1-(4-methoxyphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-fluoro--
1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0360]
1-(4-methoxyphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fluoro-
-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro
1H-imidazolo[4,5-c]pyridine;
[0361]
1-(4-methoxyphenyl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1'-bi-
phenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0362]
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-me-
thoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0363]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]py-
ridine;
[0364]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]py-
ridine;
[0365]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine-
;
[0366]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(4-methoxyp-
henyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0367]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)--
1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0368]
1-(4-methoxyphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-pheny-
l]-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0369]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]py-
ridine;
[0370]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)--
1-(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0371]
1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-
-2-fluoro-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0372]
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl-
)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0373]
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxypheny-
l)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0374]
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-7-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0375]
1-(3-aminomethylphenyl)-6-{2'-[(methylamino)methyl]-1,1'-biphenyl-4-
-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0376]
1-(3-aminomethylphenyl)-6-{2'-[(dimethylamino)methyl]-1,1'-biphenyl-
-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0377]
1-(3-aminomethylphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-1,1'--
biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0378]
1-(3-aminomethylphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'-
-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0379]
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-bipheny-
l-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0380]
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminomethyl-
phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0381]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridin-
e;
[0382]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridin-
e;
[0383]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3-am-
inomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0384]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(3-aminomethylphenyl)-
-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0385]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}phenyl)-1-(3-amino-
methylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0386]
1-(3-aminomethylphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-7-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0387]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridin-
e;
[0388]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-amin-
omethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0389]
1-(3-aminomethylphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-
-yl}phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0390]
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-7-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0391]
6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-7--
oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0392]
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-biphenyl--
4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0393]
1-(3-aminomethylphenyl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-b-
iphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0394]
1-(3-aminomethylphenyl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-
-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0395]
1-(3-aminomethylphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-flu-
oro-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridi-
ne;
[0396]
1-(3-aminomethylphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fl-
uoro-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyrid-
ine;
[0397]
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1-
'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0398]
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-am-
inomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0399]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5--
c]pyridine;
[0400]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5--
c]pyridine;
[0401]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-1-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyri-
dine;
[0402]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(3-aminomet-
hylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0403]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)--
1-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridi-
ne;
[0404]
1-(3-aminomethylphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-p-
henyl]-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0405]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5--
c]pyridine;
[0406]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)--
1-(3-aminomethylphenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridi-
ne;
[0407]
1-(3-aminomethylphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-
-yl}-2-fluoro-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine-
;
[0408]
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylph-
enyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0409]
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylp-
henyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0410]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-y-
l}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0411]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(methylamino)methyl]-1,1'-biph-
enyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0412]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(dimethylamino)methyl]-1,1'-bi-
phenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0413]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-
-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0414]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamino)methyl-
]-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine-
;
[0415]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-b-
iphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0416]
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminobenzis-
oxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0417]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]p-
yridine;
[0418]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]p-
yridine;
[0419]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3-am-
inobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridin-
e;
[0420]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(3-aminobenzisoxazol--
5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0421]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}phenyl)-1-(3-amino-
benzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0422]
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(2-methyl-1H-imidazol-1-yl)pheny-
l]-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0423]
6-(2'-{[2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1--
(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]py-
ridine;
[0424]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-amin-
obenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro
1H-imidazolo[4,5-c]pyridine;
[0425]
1-(3-aminobenzisoxazol-5'-yl)-6-(4-{2-[(methylamino)methyl]-1H-imid-
azol-1-yl}phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0426]
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5'-y-
l)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0427]
6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5'--
yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0428]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-bip-
henyl-4-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0429]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(methylamino)methyl]-3-fluoro--
1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0430]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(dimethylamino)methyl]-3-fluor-
o-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine-
;
[0431]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-
-3-fluoro-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]-
pyridine;
[0432]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamino)methyl-
]-3-fluoro-1,1-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]-
pyridine;
[0433]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-3-fluo-
ro-1,1'-biphenyl-4-yl}-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridin-
e;
[0434]
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-am-
inobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridin-
e;
[0435]
6-(2'-{([(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphen-
yl-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazo-
lo[4,5-c]pyridine;
[0436]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazol-
o[4,5-c]pyridine;
[0437]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5--
c]pyridine;
[0438]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(3-aminoben-
zisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0439]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)--
1-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]-
pyridine;
[0440]
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fl-
uoro-phenyl]-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0441]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazol-
o[4,5-c]pyridine;
[0442]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)--
1-(3-aminobenzisoxazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]-
pyridine;
[0443]
1-(3-aminobenzisoxazol-5'-yl)-6-(4-{2-[(methylamino)methyl]-1H-imid-
azol-1-yl}-2-fluoro-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]py-
ridine;
[0444]
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminobenzisox-
azol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0445]
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminobenziso-
xazol-5'-yl)-7-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]pyridine;
[0446]
3-[4,5,6,7-tetrahydro-6-[2'-[aminomethyl][1,1'-biphenyl]-4-yl]-7-ox-
o-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0447]
3-[4,5,6,7-tetrahydro-6-[2'-[[methylamino]methyl][1,1'-biphenyl]-4--
yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0448]
3-[4,5,6,7-tetrahydro-6-[2'-[[dimethylamino]methyl][1,1'-biphenyl]--
4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0449]
3-[4,5,6,7-tetrahydro-6-[2'-[[4-hydroxypiperidin-1-yl]methyl][1,1'--
biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0450]
3-[4,5,6,7-tetrahydro-6-[2'-[[N-ethyl-N-methylamino]-methyl][1,1'-b-
iphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0451]
3-[4,5,6,7-tetrahydro-6-[2'-[[pyrrolidin-1-yl]methyl][1,1'-biphenyl-
]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0452]
3-[4,5,6,7-tetrahydro-6-[2'-[[3(R)-hydroxypyrrolidin-1-yl]methyl][1-
,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0453]
3-[4,5,6,7-tetrahydro-6-[2'-[[3(S)-hydroxypyrrolidin-1-yl]methyl][1-
,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0454]
3-[4,5,6,7-tetrahydro-6-[2'-[[N-propyl-N-methylamino]methyl][1,1'-b-
iphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0455]
3-[4,5,6,7-tetrahydro-6-[2'-[[t-butylamino]methyl][1,1-biphenyl]-4--
yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0456]
3-[4,5,6,7-tetrahydro-6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-7-
-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0457]
3-[4,5,6,7-tetrahydro-6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-
-yl}phenyl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0458]
3-[4,5,6,7-tetrahydro-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-7-oxo-
-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0459]
3-[4,5,6,7-tetrahydro-6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-
-1,1'-biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0460]
3-[4,5,6,7-tetrahydro-6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-bi-
phenyl-4-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0461]
3-[4,5,6,7-tetrahydro-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-y-
l}phenyl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0462]
3-[4,5,6,7-tetrahydro-6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-7-oxo-
-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0463]
3-[4,5,6,7-tetrahydro-6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-7-ox-
o-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0464]
3-[4,5,6,7-tetrahydro-6-[2'-[aminomethyl]-3-fluoro-[1,1'-biphenyl]--
4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0465]
3-[4,5,6,7-tetrahydro-6-[2'-[[methylamino]methyl]-3-fluoro-[1,1'-bi-
phenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0466]
3-[4,5,6,7-tetrahydro-6-[2'-[[dimethylamino]methyl]-3-fluoro-[1,1'--
biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0467]
3-[4,5,6,7-tetrahydro-6-[2'-[[4-hydroxypiperidin-1-yl]methyl]-3-flu-
oro-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0468]
3-[4,5,6,7-tetrahydro-6-[2'-[[N-ethyl-N-methylamino]methyl]-3-fluor-
o-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0469]
3-[4,5,6,7-tetrahydro-6-[2'-[[pyrrolidin-1-yl]methyl]-3-fluoro-[1,1-
'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0470]
3-[4,5,6,7-tetrahydro-6-[2'-[[3(R)-hydroxypyrrolidin-1-yl]methyl]-3-
-fluoro-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzam-
ide;
[0471]
3-[4,5,6,7-tetrahydro-6-[2'-[[3(S)-hydroxypyrrolidin-1-yl]methyl]-3-
-fluoro-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzam-
ide;
[0472]
3-[4,5,6,7-tetrahydro-6-[2'-[[N-propyl-N-methylamino]methyl]-3-fluo-
ro-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0473]
3-[4,5,6,7-tetrahydro-6-[2'-[[t-butylamino]methyl]-3-fluoro-[1,1'-b-
iphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0474]
3-[4,5,6,7-tetrahydro-6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-
-phenyl}-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0475]
3-[4,5,6,7-tetrahydro-6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-
-yl}-2-fluoro-phenyl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0476]
3-[4,5,6,7-tetrahydro-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-phe-
nyl]-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0477] 3-[4,5,6,7-tetrahydro-6-(2'-{[(215
hydroxyethyl)(methyl)amino]methy-
l}-3-fluoro-1,1'-biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benz-
amide;
[0478]
3-[4,5,6,7-tetrahydro-6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluor-
o-1,1'-biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0479]
3-[4,5,6,7-tetrahydro-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-y-
l}-2-fluoro-phenyl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0480]
3-[4,5,6,7-tetrahydro-6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4--
yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide; and,
[0481]
3-[4,5,6,7-tetrahydro-6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-
-yl)-7-oxo-1H-imidazolo[4,5-c]pyridin-1-yl]benzamide;
[0482] or a pharmaceutically acceptable salt form thereof.
[0483] [15] In another preferred embodiment, the present invention
provides a novel compound selected from:
[0484]
1-(4-Methoxyphenyl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-7-oxo-1-
,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0485]
1-(4-Methoxyphenyl)-6-{2'-[(methylamino)methyl]-1,1'-biphenyl-4-yl}-
-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0486]
1-(4-Methoxyphenyl)-6-{2'-[(dimethylamino)methyl]-1,1'-biphenyl-4-y-
l}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0487]
1-(4-Methoxyphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-1,1'-biph-
enyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0488]
1-(4-Methoxyphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'-bip-
henyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0489]
1-(4-Methoxyphenyl)-6-[(2'-[(N-t-butylamino)methyl]-1,1'-biphenyl-4-
-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0490]
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(4-methoxyphen-
yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0491]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0492]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0493]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(4-me-
thoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0494]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(4-methoxyphenyl)-7-o-
xo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0495]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}phenyl)-1-(4-metho-
xyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0496]
1-(4-methoxyphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-7-oxo-1-
,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0497]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-
-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0498]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(4-meth-
oxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0499]
1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-
phenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0500]
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo-1-
,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0501]
6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-7-oxo--
1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0502]
1-(4-Methoxyphenyl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0503]
1-(4-Methoxyphenyl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-biphe-
nyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0504]
1-(4-Methoxyphenyl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-bip-
henyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0505]
1-(4-Methoxyphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-fluoro--
1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0506]
1-(4-Methoxyphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fluoro-
-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0507]
1-(4-Methoxyphenyl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1'-bi-
phenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0508]
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-me-
thoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0509]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidin-
e;
[0510]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidin-
e;
[0511]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-1-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0512]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(4-methoxyp-
henyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0513]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)--
1-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0514]
1-(4-methoxyphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-pheny-
l]-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0515]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidin-
e;
[0516]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)--
1-(4-methoxyphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0517]
1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-
-2-fluoro-phenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0518]
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl-
)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0519]
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxypheny-
l)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0520]
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-7-o-
xo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0521]
1-(3-aminomethylphenyl)-6-{2'-[(methylamino)methyl]-1,1'-biphenyl-4-
-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0522]
1-(3-aminomethylphenyl)-6-{2'-[(dimethylamino)methyl]-1,1'-biphenyl-
-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0523]
1-(3-aminomethylphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-1,1'--
biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0524]
1-(3-aminomethylphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'-
-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0525]
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-bipheny-
l-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0526]
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminomethyl-
phenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0527]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0528]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0529]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3-am-
inomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0530]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(3-aminomethylphenyl)-
-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0531]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}phenyl)-1-(3-amino-
methylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0532]
1-(3-aminomethylphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-7-o-
xo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0533]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0534]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-amin-
omethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0535]
1-(3-aminomethylphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-
-yl}phenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0536]
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-7-o-
xo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0537]
6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-7--
oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0538]
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-biphenyl--
4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0539]
1-(3-aminomethylphenyl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-b-
iphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0540]
1-(3-aminomethylphenyl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-
-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0541]
1-(3-aminomethylphenyl)-6-[2'-[(N-ethyl-N-methylamino)methyl]-3-flu-
oro-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0542]
1-(3-aminomethylphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fl-
uoro-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0543]
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1-
'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0544]
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-am-
inomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0545]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrim-
idine;
[0546]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrim-
idine;
[0547]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-1-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0548]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(3-aminomet-
hylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0549]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)--
1-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0550]
1-(3-aminomethylphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-p-
henyl]-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0551]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrim-
idine;
[0552]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)--
1-(3-aminomethylphenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0553]
1-(3-aminomethylphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-
-yl}-2-fluoro-phenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0554]
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylph-
enyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0555]
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylp-
henyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0556]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-y-
l}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0557]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(methylamino)methyl]-1,1'-biph-
enyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0558]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(dimethylamino)methyl]-1,1'-bi-
phenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0559]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-
-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0560]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamino)methyl-
]-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0561]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-1,1-bi-
phenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0562]
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminobenzis-
oxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0563]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidi-
ne;
[0564]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidi-
ne;
[0565]
6-[(2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3-a-
minobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0566]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(3-aminobenzisoxazol--
5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0567]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}phenyl)-1-(3-amino-
benzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0568]
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(2-methyl-1H-imidazol-1-yl)pheny-
l]-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0569]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidi-
ne;
[0570]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-amin-
obenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0571]
1-(3-aminobenzisoxazol-5'-yl)-6-(4-{2-[(methylamino)methyl]-1H-imid-
azol-1-yl}phenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0572]
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5'-y-
l)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0573]
6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5'--
yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0574]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-bip-
henyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0575]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(methylamino)methyl]-3-fluoro--
1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0576]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(dimethylamino)methyl]-3-fluor-
o-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0577]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-
-3-fluoro-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimid-
ine;
[0578]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamino)methyl-
]-3-fluoro-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimi-
dine;
[0579]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-3-fluo-
ro-1,1'-biphenyl-4-yl}-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0580]
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-am-
inobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0581]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d-
]pyrimidine;
[0582]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d-
]pyrimidine;
[0583]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrim-
idine;
[0584]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(3-aminoben-
zisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0585]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)--
1-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimid-
ine;
[0586]
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fl-
uoro-phenyl]-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0587]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d-
]pyrimidine;
[0588]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)--
1-(3-aminobenzisoxazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimid-
ine;
[0589]
1-(3-aminobenzisoxazol-5'-yl)-6-(4-{2-[(methylamino)methyl]-1H-imid-
azol-1-yl}-2-fluoro-phenyl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidin-
e;
[0590]
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminobenzisox-
azol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0591]
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminobenziso-
xazol-5'-yl)-7-oxo-1,6-dihydro-1H-imidazolo[4,5-d]pyrimidine;
[0592]
3-[1,6-dihydro-6-[2'-[aminomethyl][1,1'-biphenyl]-4-yl]-7-oxo-1H-im-
idazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0593]
3-[1,6-dihydro-6-[2'-[[methylamino]methyl][1,1'-biphenyl]-4-yl]-7-o-
xo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0594]
3-[1,6-dihydro-6-[2'-[[dimethylamino]methyl][1,1'-biphenyl]-4-yl]-7-
-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0595]
3-[1,6-dihydro-6-[2'-[[4-hydroxypiperidin-1-yl]methyl][1,1'-bipheny-
l]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0596]
3-[1,6-dihydro-6-[2'-[[N-ethyl-N-methylamino]methyl][1,1'-biphenyl]-
-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0597]
3-[1,6-dihydro-6-[2'-[[pyrrolidin-1-yl]methyl][1,1'-biphenyl]-4-yl]-
-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0598]
3-[1,6-dihydro-6-[2'-[[3(R)-hydroxypyrrolidin-1-yl]methyl][1,1'-bip-
henyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0599]
3-[1,6-dihydro-6-[2'-[[3(S)-hydroxypyrrolidin-1-yl]methyl][1,1'-bip-
henyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0600]
3-[1,6-dihydro-6-[2'-[[N-propyl-N-methylamino]methyl][1,1'-biphenyl-
]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0601]
3-[1,6-dihydro-6-[2'-[[t-butylamino]methyl][1,1'-biphenyl]-4-yl]-7--
oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0602]
3-[1,6-dihydro-6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-7-oxo-1H-
-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0603]
3-[1,6-dihydro-6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}phe-
nyl)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0604]
3-[1,6-dihydro-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-7-oxo-1H-imi-
dazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0605]
3-[1,6-dihydro-6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-b-
iphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0606]
3-[1,6-dihydro-6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl--
4-yl)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0607]
3-[1,6-dihydro-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}pheny-
l)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0608]
3-[1,6-dihydro-6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-7-oxo-1H-imi-
dazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0609]
3-[1,6-dihydro-6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-7-oxo-1H-im-
idazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0610]
3-[1,6-dihydro-6-[2'-[aminomethyl]-3-fluoro-[1,1'-biphenyl]-4-yl]-7-
-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0611]
3-[1,6-dihydro-6-[2'-[[methylamino]methyl]-3-fluoro-[1,1'-biphenyl]-
-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0612]
3-[1,6-dihydro-6-[2'-[[dimethylamino]methyl]-3-fluoro-[1,1'-bipheny-
l]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0613]
3-[1,6-dihydro-6-[2'-[[4-hydroxypiperidin-1-yl]methyl]-3-fluoro-[1,-
1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0614]
3-[1,6-dihydro-6-[2'-[[N-ethyl-N-methylamino]methyl]-3-fluoro-[1,1'-
-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0615]
3-[1,6-dihydro-6-[2'-[[pyrrolidin-1-yl]methyl]-3-fluoro[1,1'-biphen-
yl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0616]
3-[1,6-dihydro-6-[2'-[[3(R)-hydroxypyrrolidin-1-yl]methyl]-3-fluoro-
-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0617]
3-[1,6-dihydro-6-[2'-[[3(S)-hydroxypyrrolidin-1-yl]methyl]-3-fluoro-
-[1,1'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0618]
3-[1,6-dihydro-6-[2'-[[N-propyl-N-methylamino]methyl]-3-fluoro-[1,1-
'-biphenyl]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0619]
3-[1,6-dihydro-6-[2'-[[t-butylamino]methyl]-3-fluoro-[1,1'-biphenyl-
]-4-yl]-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0620]
3-[1,6-dihydro-6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl-
}-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0621]
3-[1,6-dihydro-6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2--
fluoro-phenyl)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0622]
3-[1,6-dihydro-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-phenyl]-7--
oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0623]
3-[1,6-dihydro-6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluo-
ro-1,1'-biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-lyl]benzamide;
[0624]
3-[1,6-dihydro-6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'--
biphenyl-4-yl)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0625]
3-[1,6-dihydro-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-2-fl-
uoro-phenyl)-7-oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0626]
3-[1,6-dihydro-6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4yl)-7-ox-
o-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0627]
3-[1,6-dihydro-6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-7--
oxo-1H-imidazolo[4,5-d]pyrimidin-1-yl]benzamide;
[0628] or a pharmaceutically acceptable salt form thereof.
[0629] [16] In another preferred embodiment, the present invention
provides a novel compound selected from:
[0630]
1-(4-methoxyphenyl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-oxo-4,5-
,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0631]
1-(4-methoxyphenyl)-6-{2'-[(methylamino)methyl]-1,1'-biphenyl-4-yl}-
-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0632]
1-(4-methoxyphenyl)-6-{2'-[(dimethylamino)methyl]-1,1'-biphenyl-4-y-
l}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0633]
1-(4-methoxyphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-1,1'-biph-
enyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0634]
1-(4-methoxyphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'-bip-
henyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0635]
1-(4-methoxyphenyl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-biphenyl-4--
yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0636]
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(4-methoxyphen-
yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0637]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0638]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0639]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(4-me-
thoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0640]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(4-methoxyphenyl)-8-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0641]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl]phenyl)-1-(4-metho-
xyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0642]
1-(4-methoxyphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-8-oxo-4-
,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0643]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-
-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0644]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(4-meth-
oxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0645]
1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-
phenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0646]
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-8-oxo-4-
,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0647]
6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl)-8-oxo--
4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0648]
1-(4-methoxyphenyl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0649]
1-(4-methoxyphenyl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-biphe-
nyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0650]
1-(4-methoxyphenyl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-bip-
henyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0651]
1-(4-methoxyphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-fluoro--
1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0652]
1-(4-methoxyphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fluoro-
-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0653]
1-(4-methoxyphenyl)-6-[(2'-[(N-t-butylamino)methyl]-3-fluoro-1,1'-b-
iphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0654]
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-me-
thoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0655]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]az-
epine;
[0656]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]az-
epine;
[0657]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-1-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0658]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(4-methoxyp-
henyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0659]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)--
1-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0660]
1-(4-methoxyphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-pheny-
l]-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0661]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]az-
epine;
[0662]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)--
1-(4-methoxyphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0663]
1-(4-methoxyphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-yl}-
-2-fluoro-phenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0664]
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxyphenyl-
)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0665]
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(4-methoxypheny-
l)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0666]
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-yl}-8-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0667]
1-(3-aminomethylphenyl)-6-{2'-[(methylamino)methyl]-1,1'-biphenyl-4-
-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0668]
1-(3-aminomethylphenyl)-6-{2'-[(dimethylamino)methyl]-1,1'-biphenyl-
-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0669]
1-(3-aminomethylphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-1,1'--
biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0670]
1-(3-aminomethylphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-1,1'-
-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0671]
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-bipheny-
l-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0672]
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminomethyl-
phenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0673]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine-
;
[0674]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine-
;
[0675]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3-am-
inomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0676]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(3-aminomethylphenyl)-
-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0677]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}phenyl)-1-(3-amino-
methylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0678]
1-(3-aminomethylphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-8-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0679]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine-
;
[0680]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-amin-
omethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0681]
1-(3-aminomethylphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-
-yl}phenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0682]
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-8-o-
xo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0683]
6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminomethylphenyl)-8--
oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0684]
1-(3-aminomethylphenyl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-biphenyl--
4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0685]
1-(3-aminomethylphenyl)-6-{2'-[(methylamino)methyl]-3-fluoro-1,1'-b-
iphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0686]
1-(3-aminomethylphenyl)-6-{2'-[(dimethylamino)methyl]-3-fluoro-1,1'-
-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0687]
1-(3-aminomethylphenyl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-3-flu-
oro-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepin-
e;
[0688]
1-(3-aminomethylphenyl)-6-{2'-[(N-methyl-N-propylamino)methyl]-3-fl-
uoro-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepi-
ne;
[0689]
1-(3-aminomethylphenyl)-6-{2'-[(N-t-butylamino)methyl]-3-fluoro-1,1-
'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0690]
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-am-
inomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0691]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5--
c]azepine;
[0692]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5--
c]azepine;
[0693]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-1-(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azep-
ine;
[0694]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(3-aminomet-
hylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0695]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)--
1-(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepin-
e;
[0696]
1-(3-aminomethylphenyl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-p-
henyl]-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0697]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5--
c]azepine;
[0698]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)--
1-(3-aminomethylphenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepin-
e;
[0699]
1-(3-aminomethylphenyl)-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-
-yl}-2-fluoro-phenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0700]
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylph-
enyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0701]
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminomethylp-
henyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0702]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[aminomethyl]-1,1'-biphenyl-4-y-
l}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0703]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(methylamino)methyl]-1,1'-biph-
enyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0704]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(dimethylamino)methyl]-1,1'-bi-
phenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0705]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-
-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0706]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamino)methyl-
]-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0707]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-1,1'-b-
iphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0708]
6-(2'-{[1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-(3-aminobenzis-
oxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0709]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]a-
zepine;
[0710]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]a-
zepine;
[0711]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-1,1'-biphenyl-4-yl}-1-(3-am-
inobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine-
;
[0712]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-1-(3-aminobenzisoxazol--
5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0713]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl)phenyl}-1-(3-amino-
benzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0714]
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(2-methyl-1H-imidazol-1-yl)pheny-
l]-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0715]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-
-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]a-
zepine;
[0716]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-biphenyl-4-yl)-1-(3-amin-
obenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0717]
1-(3-aminobenzisoxazol-5'-yl)-6-(4-{2-[(methylamino)methyl]-1H-imid-
azol-1-yl}phenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0718]
6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5'-y-
l)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0719]
6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-1-(3-aminobenzisoxazol-5'--
yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0720]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[aminomethyl]-3-fluoro-1,1'-bip-
henyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0721]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(methylamino)methyl]-3-fluoro--
1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0722]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(dimethylamino)methyl]-3-fluor-
o-1,1'-biphenyl-4-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0723]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-ethyl-N-methylamino)methyl]-
-3-fluoro-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]-
azepine;
[0724]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-methyl-N-propylamino)methyl-
]-3-fluoro-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c-
]azepine;
[0725]
1-(3-aminobenzisoxazol-5'-yl)-6-{2'-[(N-t-butylamino)methyl]-3-fluo-
ro-1,1'-biphenyl-4-yl}-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine-
;
[0726]
6-(2'-{[1-pyrrolidinyl]methyl}-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-am-
inobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine-
;
[0727]
6-(2'-{[(3S)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazol-
o[4,5-c]azepine;
[0728]
6-(2'-{[(3R)-3-hydroxy-1-pyrrolidinyl]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazol-
o[4,5-c]azepine;
[0729]
6-{2'-[(4-hydroxy-1-piperidinyl)methyl]-3-fluoro-1,1'-biphenyl-4-yl-
}-1-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5--
c]azepine;
[0730]
6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-phenyl}-1-(3-aminoben-
zisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0731]
6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-yl}-2-fluoro-phenyl)--
1-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]-
azepine;
[0732]
1-(3-aminobenzisoxazol-5'-yl)-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fl-
uoro-phenyl]-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0733]
6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-3-fluoro-1,1'-bipheny-
l-4-yl)-1-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazol-
o[4,5-c]azepine;
[0734]
6-(2'-{[(2-hydroxyethyl)amino]methyl}-3-fluoro-1,1'-biphenyl-4-yl)--
1-(3-aminobenzisoxazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]-
azepine;
[0735]
1-(3-aminobenzisoxazol-5'-yl)-6-(4-{2-[(methylamino)methyl]-1H-imid-
azol-1-yl}-2-fluoro-phenyl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]az-
epine;
[0736]
6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminobenzisox-
azol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0737]
6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-yl)-1-(3-aminobenziso-
xazol-5'-yl)-8-oxo-4,5,6,7-tetrahydro-1H-imidazolo[4,5-c]azepine;
[0738]
3-[4,5,6,7-tetrahydro-6-[2'-[aminomethyl][1,1'-biphenyl]-4-yl]-8-ox-
o-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0739]
3-[4,5,6,7-tetrahydro-6-[2'-[[methylamino]methyl][1,1'-biphenyl]-4--
yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0740]
3-[4,5,6,7-tetrahydro-6-[2'-[[dimethylamino]methyl][1,1'-biphenyl]--
4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0741]
3-[4,5,6,7-tetrahydro-6-[2'-[[4-hydroxypiperidin-1-yl]methyl][1,1'--
biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0742]
3-[4,5,6,7-tetrahydro-6-[2'-[[N-ethyl-N-methylamino]-methyl][1,1'-b-
iphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0743]
3-[4,5,6,7-tetrahydro-6-[2'-[[pyrrolidin-1-yl]methyl][1,1'-biphenyl-
]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0744]
3-[4,5,6,7-tetrahydro-6-[2'-[[3(R)-hydroxypyrrolidin-1-yl]methyl][1-
,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0745]
3-[4,5,6,7-tetrahydro-6-[2'-[[3(S)-hydroxypyrrolidin-1-yl]methyl][1-
,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0746]
3-[4,5,6,7-tetrahydro-6-[2'-[[N-propyl-N-methylamino]methyl][1,1'-b-
iphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0747]
3-[4,5,6,7-tetrahydro-6-[2'-[[t-butylamino]methyl][1,1'-biphenyl]-4-
-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0748]
3-[4,5,6,7-tetrahydro-6-{4-[3-(aminosulfonyl)-4-pyridinyl]phenyl}-8-
-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0749]
3-[4,5,6,7-tetrahydro-6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-
-yl}phenyl)-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0750]
3-[4,5,6,7-tetrahydro-6-[4-(2-methyl-1H-imidazol-1-yl)phenyl]-8-oxo-
-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0751]
3-[4,5,6,7-tetrahydro-6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-
-1,1'-biphenyl-4-yl)
[0752] 8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0753]
3-[4,5,6,7-tetrahydro-6-(2'-{[(2-hydroxyethyl)amino]methyl}-1,1'-bi-
phenyl-4-yl)-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0754]
3-[4,5,6,7-tetrahydro-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-y-
l}phenyl)-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0755]
3-[4,5,6,7-tetrahydro-6-(2'-aminosulfonyl-1,1'-biphenyl-4-yl)-8-oxo-
-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0756]
3-[4,5,6,7-tetrahydro-6-(2'-methylsulfonyl-1,1'-biphenyl-4-yl)-8-ox-
o-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0757]
3-[4,5,6,7-tetrahydro-6-[2'-[aminomethyl]-3-fluoro-[1,1'-biphenyl]--
4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0758]
3-[4,5,6,7-tetrahydro-6-[2'-[[methylamino]methyl]-3-fluoro[1,1'-bip-
henyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0759]
3-[4,5,6,7-tetrahydro-6-[2'-[[dimethylamino]methyl]-3-fluoro-[1,1'--
biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0760]
3-[4,5,6,7-tetrahydro-6-[2'-[[4-hydroxypiperidin-1-yl]methyl]-3-flu-
oro-[1,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0761]
3-[4,5,6,7-tetrahydro-6-[2'-[[N-ethyl-N-methylamino]methyl]-3-fluor-
o-[1,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0762]
3-[4,5,6,7-tetrahydro-6-[2'-[[pyrrolidin-1-yl]methyl]-3-fluoro-[1,1-
'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0763]
3-[4,5,6,7-tetrahydro-6-[2'-[[3(R)-hydroxypyrrolidin-1-yl]methyl]-3-
-fluoro-[1,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzami-
de;
[0764]
3-[4,5,6,7-tetrahydro-6-[2'-[[3(S)-hydroxypyrrolidin-1-yl]methyl]-3-
-fluoro-[1,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzami-
de;
[0765]
3-[4,5,6,7-tetrahydro-6-[2'-[[N-propyl-N-methylamino]methyl]-3-fluo-
ro-[1,1'-biphenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0766]
3-[4,5,6,7-tetrahydro-6-[2'-[[t-butylamino]methyl]-3-fluoro[1,1'-bi-
phenyl]-4-yl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0767]
3-[4,5,6,7-tetrahydro-6-{4-[3-(aminosulfonyl)-4-pyridinyl]-2-fluoro-
-phenyl}-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0768]
3-[4,5,6,7-tetrahydro-6-(4-{2-[(dimethylamino)methyl]-1H-imidazol-1-
-yl}-2-fluoro-phenyl)-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0769]
3-[4,5,6,7-tetrahydro-6-[4-(2-methyl-1H-imidazol-1-yl)-2-fluoro-phe-
nyl]-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0770]
3-[4,5,6,7-tetrahydro-6-(2'-{[(2-hydroxyethyl)(methyl)amino]methyl}-
-3-fluoro-1,1'biphenyl-4-yl)-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamid-
e;
[0771]
3-[4,5,6,7-tetrahydro-6-(2'-{((2-hydroxyethyl)amino]methyl}-3-fluor-
o-1,1'-biphenyl-4-yl)-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0772]
3-[4,5,6,7-tetrahydro-6-(4-{2-[(methylamino)methyl]-1H-imidazol-1-y-
l}-2-fluoro-phenyl)-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0773]
3-[4,5,6,7-tetrahydro-6-(2'-aminosulfonyl-3-fluoro-1,1'-biphenyl-4--
yl)-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0774]
3-[4,5,6,7-tetrahydro-6-(2'-methylsulfonyl-3-fluoro-1,1'-biphenyl-4-
-yl)-8-oxo-1H-imidazolo[4,5-c]azepin-1-yl]benzamide;
[0775] or a pharmaceutically acceptable salt form thereof.
[0776] In another embodiment, the present invention provides novel
pharmaceutical compositions, comprising: a pharmaceutically
acceptable carrier and a therapeutically effective amount of a
compound of the present invention or a pharmaceutically acceptable
salt form thereof.
[0777] In another embodiment, the present invention provides a
novel method for treating a thromboembolic disorder, comprising:
administering to a patient in need thereof a therapeutically
effective amount of a compound of the present invention or a
pharmaceutically acceptable salt form thereof.
[0778] In another embodiment, the present invention provides novel
compounds as described above for use in therapy.
[0779] In another embodiment, the present invention provides the
use of novel compounds as described above for the manufacture of a
medicament for the treatment of a thromboembolic disorder.
Definitions
[0780] The compounds herein described may have asymmetric centers.
Compounds of the present invention containing an asymmetrically
substituted atom may be isolated in optically active or racemic
forms. It is well known in the art how to prepare optically active
forms, such as by resolution of racemic forms or by synthesis from
optically active starting materials. Many geometric isomers of
olefins, C.dbd.N double bonds, and the like can also be present in
the compounds described herein, and all such stable isomers are
contemplated in the present invention. Cis and trans geometric
isomers of the compounds of the present invention are described and
may be isolated as a mixture of isomers or as separated isomeric
forms. All chiral, diastereomeric, racemic forms and all geometric
isomeric forms of a structure are intended, unless the specific
stereochemistry or isomeric form is specifically indicated. All
processes used to prepare compounds of the present invention and
intermediates made therein are considered to be part of the present
invention.
[0781] The term "substituted," as used herein, means that any one
or more hydrogens on the designated atom is replaced with a
selection from the indicated group, provided that the designated
atom's normal valency is not exceeded, and that the substitution
results in a stable compound. When a substituent is keto (i.e.,
.dbd.O), then 2 hydrogens on the atom are replaced. Keto
substituents are not present on aromatic moieties.
[0782] The present invention is intended to include all isotopes of
atoms occurring in the present compounds. Isotopes include those
atoms having the same atomic number but different mass numbers. By
way of general example and without limitation, isotopes of hydrogen
include tritium and deuterium. Isotopes of carbon include C-13 and
C-14.
[0783] When any variable (e.g., R.sup.6) occurs more than one time
in any constituent or formula for a compound, its definition at
each occurrence is independent of its definition at every other
occurrence. Thus, for example, if a group is shown to be
substituted with 0-2 R.sup.6, then said group may optionally be
substituted with up to two R.sup.6 groups and R.sup.6 at each
occurrence is selected independently from the definition of
R.sup.6. Also, combinations of substituents and/or variables are
permissible only if such combinations result in stable
compounds.
[0784] When a bond to a substituent is shown to cross a bond
connecting two atoms in a ring, then such substituent may be bonded
to any atom on the ring. When a substituent is listed without
indicating the atom via which such substituent is bonded to the
rest of the compound of a given formula, then such substituent may
be bonded via any atom in such substituent. Combinations of
substituents and/or variables are permissible only if such
combinations result in stable compounds.
[0785] As used herein, "alkyl" is intended to include both branched
and straight-chain saturated aliphatic hydrocarbon groups having
the specified number of carbon atoms. C.sub.1-10 alkyl, is intended
to include C.sub.1, C.sub.2, C.sub.3, C.sub.4, C5, C.sub.6,
C.sub.7, C.sub.8, C.sub.9, and C.sub.10alkyl groups. Examples of
alkyl include, but are not limited to, methyl, ethyl, n-propyl,
i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, and s-pentyl.
"Haloalkyl" is intended to include both branched and straight-chain
saturated aliphatic hydrocarbon groups having the specified number
of carbon atoms, substituted with 1 or more halogen (for example
--C.sub.vF.sub.w where v=1 to 3 and w=1 to (2v+1)). Examples of
haloalkyl include, but are not limited to, trifluoromethyl,
trichloromethyl, pentafluoroethyl, and pentachloroethyl. "Alkoxy"
represents an alkyl group as defined above with the indicated
number of carbon atoms attached through an oxygen bridge.
C.sub.1-10 alkoxy, is intended to include C.sub.1, C.sub.2,
C.sub.3, C.sub.4, C.sub.5, C.sub.6, C.sub.7, C.sub.8, C.sub.9, and
C.sub.10 alkoxy groups. Examples of alkoxy include, but are not
limited to, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy,
s-butoxy, t-butoxy, n-pentoxy, and s-pentoxy. "Cycloalkyl" is
intended to include saturated ring groups, such as cyclopropyl,
cyclobutyl, or cyclopentyl. C.sub.3-7 cycloalkyl is intended to
include C.sub.3, C.sub.4, C.sub.5, C.sub.6, and C.sub.7 cycloalkyl
groups. Alkenyl" is intended to include hydrocarbon chains of
either straight or branched configuration and one or more
unsaturated carbon-carbon bonds that may occur in any stable point
along the chain, such as ethenyl and propenyl. C.sub.2-10 alkenyl
is intended to include C.sub.2, C.sub.3, C.sub.4, C.sub.5, C.sub.6,
C.sub.7, C8, C.sub.9, and C.sub.10 alkenyl groups. "Alkynyl" is
intended to include hydrocarbon chains of either straight or
branched configuration and one or more triple carbon-carbon bonds
that may occur in any stable point along the chain, such as ethynyl
and propynyl. C.sub.2-10 Alkynyl is intended to include C2, C3,
C.sub.4, C.sub.5, C.sub.6, C.sub.7, C.sub.8, C.sub.9, and
C.sub.1-0alkynyl groups.
[0786] "Halo" or "halogen" as used herein refers to fluoro, chloro,
bromo, and iodo; and "counterion" is used to represent a small,
negatively charged species such as chloride, bromide, hydroxide,
acetate, and sulfate.
[0787] As used herein, "carbocycle" or "carbocyclic residue" is
intended to mean any stable 3, 4, 5, 6, or 7-membered monocyclic or
bicyclic or 7, 8, 9, 10, 11, 12, or 13-membered bicyclic or
tricyclic, any of which may be saturated, partially unsaturated, or
aromatic. Examples of such carbocycles include, but are not limited
to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,
adamantyl, cyclooctyl, [3.3.0]bicyclooctane, [4.3.0]bicyclononane,
[4.4.0]bicyclodecane, [2.2.2]bicyclooctane, fluorenyl, phenyl,
naphthyl, indanyl, adamantyl, and tetrahydronaphthyl.
[0788] As used herein, the term "heterocycle" or "heterocyclic
system" is intended to mean a stable 5, 6, or 7-membered monocyclic
or bicyclic or 7, 8, 9, or 10-membered bicyclic heterocyclic ring
which is saturated, partially unsaturated or unsaturated
(aromatic), and which consists of carbon atoms and 1, 2, 3, or 4
heteroatoms independently selected from the group consisting of N,
NH, O and S and including any bicyclic group in which any of the
above-defined heterocyclic rings is fused to a benzene ring. The
nitrogen and sulfur heteroatoms may optionally be oxidized. The
heterocyclic ring may be attached to its pendant group at any
heteroatom or carbon atom that results in a stable structure. The
heterocyclic rings described herein may be substituted on carbon or
on a nitrogen atom if the resulting compound is stable. A nitrogen
in the heterocycle may optionally be quaternized. It is preferred
that when the total number of S and O atoms in the heterocycle
exceeds 1, then these heteroatoms are not adjacent to one another.
It is preferred that the total number of S and O atoms in the
heterocycle is not more than 1. As used herein, the term "aromatic
heterocyclic system" or "heteroaryl" is intended to mean a stable
5, 6, or 7-membered monocyclic or bicyclic or 7, 8, 9, or
10-membered bicyclic heterocyclic aromatic ring which consists of
carbon atoms and 1, 2, 3, or 4 heteroatoms independently selected
from the group consisting of N, NH, O and S. It is to be noted that
total number of S and O atoms in the aromatic heterocycle is not
more than 1.
[0789] Examples of heterocycles include, but are not limited to,
acridinyl, azocinyl, benzimidazolyl, benzofuranyl,
benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzoxazolinyl,
benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl,
benzisothiazolyl, benzimidazolinyl, carbazolyl, 4aH-carbazolyl,
carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl,
2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran,
furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl,
1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl,
3H-indolyl, isatinoyl, isobenzofuranyl, isochromanyl, isoindazolyl,
isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl,
methylenedioxyphenyl, morpholinyl, naphthyridinyl,
octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl,
1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl,
oxazolidinyl, oxazolyl, oxindolyl, pyrimidinyl, phenanthridinyl,
phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathinyl,
phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, piperidonyl,
4-piperidonyl, piperonyl, pteridinyl, purinyl, pyranyl, pyrazinyl,
pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole,
pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl,
pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl,
quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl,
tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl,
tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl,
1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl,
thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl,
thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl,
1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, and xanthenyl.
Also included are fused ring and spiro compounds containing, for
example, the above heterocycles.
[0790] The phrase "pharmaceutically acceptable" is employed herein
to refer to those compounds, materials, compositions, and/or dosage
forms which are, within the scope of sound medical judgment,
suitable for use in contact with the tissues of human beings and
animals without excessive toxicity, irritation, allergic response,
or other problem or complication, commensurate with a reasonable
benefit/risk ratio.
[0791] As used herein, "pharmaceutically acceptable salts" refer to
derivatives of the disclosed compounds wherein the parent compound
is modified by making acid or base salts thereof. Examples of
pharmaceutically acceptable salts include, but are not limited to,
mineral or organic acid salts of basic residues such as amines;
alkali or organic salts of acidic residues such as carboxylic
acids; and the like. The pharmaceutically acceptable salts include
the conventional non-toxic salts or the quaternary ammonium salts
of the parent compound formed, for example, from nontoxic inorganic
or organic acids. For example, such conventional non-toxic salts
include those derived from inorganic acids such as hydrochloric,
hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like;
and the salts prepared from organic acids such as acetic,
propionic, succinic, glycolic, stearic, lactic, malic, tartaric,
citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic,
glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic,
fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic,
oxalic, isethionic, and the like.
[0792] The pharmaceutically acceptable salts of the present
invention can be synthesized from the parent compound that contains
a basic or acidic moiety by conventional chemical methods.
Generally, such salts can be prepared by reacting the free acid or
base forms of these compounds with a stoichiometric amount of the
appropriate base or acid in water or in an organic solvent, or in a
mixture of the two; generally, non-aqueous media like ether, ethyl
acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists
of suitable salts are found in Remington's Pharmaceutical Sciences,
17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418, the
disclosure of which is hereby incorporated by reference.
[0793] Since prodrugs are known to enhance numerous desirable
qualities of pharmaceuticals (e.g., solubility, bioavailability,
manufacturing, etc . . . ) the compounds of the present invention
may be delivered in prodrug form. Thus, the present invention is
intended to cover prodrugs of the presently claimed compounds,
methods of delivering the same and compositions containing the
same. "Prodrugs" are intended to include any covalently bonded
carriers that release an active parent drug of the present
invention in vivo when such prodrug is administered to a mammalian
subject. Prodrugs the present invention are prepared by modifying
functional groups present in the compound in such a way that the
modifications are cleaved, either in routine manipulation or in
vivo, to the parent compound. Prodrugs include compounds of the
present invention wherein a hydroxy, amino, or sulfhydryl group is
bonded to any group that, when the prodrug of the present invention
is administered to a mammalian subject, it cleaves to form a free
hydroxyl, free amino, or free sulfhydryl group, respectively.
Examples of prodrugs include, but are not limited to, acetate,
formate and benzoate derivatives of alcohol and amine functional
groups in the compounds of the present invention. Preferred
prodrugs are amidine prodrugs wherein D is C(.dbd.NR.sup.7)NH.sub.2
or its tautomer C(.dbd.NH)NHR.sup.7 and R.sup.7 is selected from
OH, C.sub.1-4 alkoxy, C.sub.6-10 aryloxy, C.sub.1-4 alkoxycarbonyl,
C.sub.6-10 aryloxycarbonyl, C.sub.6-10 arylmethylcarbonyl,
C.sub.1-4 alkylcarbonyloxy C.sub.1-4 alkoxycarbonyl, and C.sub.6-10
arylcarbonyloxy C.sub.1-4 alkoxycarbonyl. More preferred prodrugs
are where R.sup.7 is OH, methoxy, ethoxy, benzyloxycarbonyl,
methoxycarbonyl, and methylcarbonyloxymethoxycarbonyl.
[0794] "Stable compound" and "stable structure" are meant to
indicate a compound that is sufficiently robust to survive
isolation to a useful degree of purity from a reaction mixture, and
formulation into an efficacious therapeutic agent.
[0795] "Substituted" is intended to indicate that one or more
hydrogens on the atom indicated in the expression using
"substituted" is replaced with a selection from the indicated
group(s), provided that the indicated atom's normal valency is not
exceeded, and that the substitution results in a stable compound.
When a substituent is keto (i.e., .dbd.O) group, then 2 hydrogens
on the atom are replaced.
[0796] As used herein, "treating" or "treatment" cover the
treatment of a disease-state in a mammal, particularly in a human,
and include: (a) preventing the disease-state from occurring in a
mammal, in particular, when such mammal is predisposed to the
disease-state but has not yet been diagnosed as having it; (b)
inhibiting the disease-state, i.e., arresting it development;
and/or (c) relieving the disease-state, i.e., causing regression of
the disease state.
[0797] "Therapeutically effective amount" is intended to include an
amount of a compound of the present invention or an amount of the
combination of compounds claimed effective to inhibit factor Xa.
The combination of compounds is preferably a synergistic
combination. Synergy, as described, for example, by Chou and
Talalay, Adv. Enzyme Regul. 1984, 22:27-55, occurs when the effect
(in this case, inhibition of factor Xa) of the compounds when
administered in combination is greater than the additive effect of
the compounds when administered alone as a single agent. In
general, a synergistic effect is most clearly demonstrated at
sub-optimal concentrations of the compounds. Synergy can be in
terms of lower cytotoxicity, increased antiviral effect, or some
other beneficial effect of the combination compared with the
individual components.
Synthesis
[0798] The compounds of the present invention can be prepared in a
number of ways known to one skilled in the art of organic
synthesis. The compounds of the present invention can be
synthesized using the methods described below, together with
synthetic methods known in the art of synthetic organic chemistry,
or by variations thereon as appreciated by those skilled in the
art. Preferred methods include, but are not limited to, those
described below. The reactions are performed in a solvent
appropriate to the reagents and materials employed and suitable for
the transformations being effected. It will be understood by those
skilled in the art of organic synthesis that the functionality
present on the molecule should be consistent with the
transformations proposed. This will sometimes require a judgment to
modify the order of the synthetic steps or to select one particular
process scheme over another in order to obtain a desired compound
of the invention. It will also be recognized that another major
consideration in the planning of any synthetic route in this field
is the judicious choice of the protecting group used for protection
of the reactive functional groups present in the compounds
described in this invention. An authoritative account describing
the many alternatives to the trained practitioner is Greene and
Wuts (Protective Groups In Organic Synthesis, Wiley and Sons,
1991). All references cited herein are hereby incorporated in their
entirety herein by reference.
[0799] The compounds of the present invention represented by
Formula I consist of a group "G-(CH.sub.2).sub.s-" and a group
"-A-B" attached to a [5,6]- or [5,7]-heterobicyclic core structure
of varying composition. The five-membered ring is imidazole and
this ring can be fused to a variety of six- or seven membered rings
including but not limited to piperidinone, pyridinone,
pyrimidinone, pyrimidinedione, pyranone, diazepinone,
diazepinedione. The following discussion and schemes will describe
methods for the syntheses of the heterobicyclic cores and
attachment to the groups "G-(CH.sub.2).sub.s-" and "-A-B".
[0800] Bicyclic compounds of the present invention in which the
five membered ring is imidazole and the G-containing group is
attached to a nitrogen atom and M.sub.3 is attached through a C--N
linkage can be prepared as shown in WO00/39131, specifically Scheme
XXI therein.
[0801] Bicyclic compounds of the present invention in which the
five membered ring is imidazole and the G-containing group is
attached to a nitrogen atom and M.sub.3 is attached through a C--C
linkage can be prepared as shown in Scheme I. 32
[0802] 3-Hydroxy-2-nitro-2-cyclohexen-1-one I (Krebs, E. P.; et al.
Helv. Chim. Acta 1979, 62, 497-506) upon nitro reduction and
acylation with acetic formic anhydride gives formamide II which is
then cyclized to a 2-substituted
3,5,6,7-tetrahydro-benzimidazol-4-one III in the presence of formic
acid and R.sup.1a carboxamide. Imidazole alkylation (s>0) or
arylation (s=0) is accomplished using standard methodology to give
IV. Introduction of M.sub.3 is performed using enolate arylation
conditions (Buchwald, S. L. J. Am. Chem. Soc. 1997, 119,
11108-11109) to furnish V. 33
[0803] Scheme II describes synthesis of VII, the 5,6-dihydro
version of V, depending on whether the G-group is directly attached
(s=0) to the imidazole or not (s>0). For the directly attached
G-group (s=0), one begins from V and bromination at C-7 followed by
a base assisted elimination and isomerization of the double bond
gives VI. For non-direct G-group attachment (s>0) one begins
from 3-bromo-6-nitro-o-anisidine. After a Pd.sup.0 catalyzed C--C
cross-coupling with boronic acid M.sub.3 to give IX, an alkylation
of aniline IX would afford X. Imidazole ring formation could be
completed using standard conditions followed by methyl ether
deprotection to give VII. 34
[0804] Scheme III shows the synthesis of imidazo-piperdine XIV.
Beginning from chloro-nitro-imidazole X (Sarasin, J. Helv. Chim.
Acta 1924, 7, 713) and through standard synthetic manipulations
(Tennant, G. J. Chem Soc., Perkin Trans. 1, 1999, 629-640) aldehyde
XI is made. Upon nitro group reduction and condensation
hydroxyl-amine XII is constructed. Alkylation of nitrogen is
completed with bromide Z.sup.2-Br to arrive at XIV. 35
[0805] Scheme IV demonstrates how compound XIX can be made from
2,4-dimethoxy-6-nitroaniline XV (Gengnagel, K.; et al. Eur. Pat.
Appl. (1982) EP 54228 A1) through a series of steps similar to
those shown in Scheme II. 36
[0806] Scheme V outlines the conversion of XIII to XXI via
MnO.sub.2 oxidation followed by alkylation. Alternatively, XIV
could be directly oxidized to XXIV. 37
[0807] Scheme VI provides for a route to imidazopyridinones such as
XXIX. Following methodology similar to that outlined in Scheme III,
one could start from a compound such as X to give XXV. Using
reported methodology (Tennant, G. J. Chem Soc., Perkin Trans. 1,
1999, 629-640) compound XXVI could be made via alkylation of XXV.
Reduction and ring closure yields XXVII which could be alkylated to
afford XXVIII. 38
[0808] Scheme VII provides for a route to compound XXXIV, an
imidazo[4,5b]azepinedione. From compound X through steps described
earlier one could make XXX. Acylation and teatment with base will
induce cyclization to both XXXII and XXXIII. Reduction of the
alcohol and introduction of M.sub.3 is performed using enolate
arylation conditions (Buchwald, S. L. J. Am. Chem. Soc. 1997, 119,
11108-11109) to furnish XXXIV.
[0809] The A-B moieties can be prepared by methods known to those
of skill in the art. The following publications, the contents of
which are incorporated herein by reference, describe and exemplify
means of preparing A-B moieties: WO97/23212, WO97/30971,
WO97/38984, WO98/06694, WO98/01428, WO98/28269, WO98/28282,
WO99/12903, WO98/57934, WO98/57937, WO98/57951, WO99/32454,
WO99/50255, WO00/39131, WO00/38683, WO00/39102, WO01/05784, and
WO0/39108.
[0810] Other features of the invention will become apparent in the
course of the following descriptions of exemplary embodiments that
are given for illustration of the invention and are not intended to
be limiting thereof.
EXAMPLES
[0811] Proton NMR spectra were obtained on a Bruker AC 300 or
Bruker AMX 500 spectrometer and were referenced to
tetramethylsilane. Mass spectra were obtained on a Shimadzu QP-5000
mass spectrometer (CI or EI) or Perkin Elmer Sciex 100 atmospheric
pressure ionization (API) spectrometer. HPLC analyses were obtained
using a Rainin Dynamax C18 column with UV detection at 230 nm using
a standard gradient program.
Example 1
7-(3-Aminomethyl-phenyl)-1-(2'-methanesulfonyl-biphenyl-4-yl)-3-propyl-3,7-
-dihydro-purine-2,6 dione
[0812] 39
[0813] 2,6-Dioxo-3-propyl-1,2,3,6-tetrahydro-purine-7-carboxylic
Acid tert-Butyl Ester (2): A 50-mL round bottom flask equipped with
a stir bar was charged with xanthine 1 (974 mg, 5.0 mmol), DMF (16
mL) and cooled to 0.degree. C. The stirred suspension was treated
with i-Pr.sub.2NEt (1.7 mL, 10 mmol), Boc.sub.2O (1.6 g, 7.5 mmol)
and catalytic amount of DMAP (65 mg). The reaction was allowed to
warm to 25.degree. C. and, after 5 h, the solution was partitioned
between brine (50 mL) and EtOAc (200 mL). The aqueous layer was
extracted with EtOAc (2.times.50 mL) and the combined organic
extracts were dried (MgSO.sub.4), filtered, and concentrated in
vacuo. Chromatography of the residue on silica (40-50%
EtOAc/hexanes) provided 2 (398 mg, 28%) as a white solid: .sup.1H
NMR (300 MHz, CDCl.sub.3) .delta. 8.49 (br s, 1H), 8.23 (s, 1H),
4.03 (t, J=7.4 Hz, 2H), 1.75 (m, 2H), 1.64 (s, 9H), 0.94 (t, J=7.4
Hz, 6H).
[0814]
1-(4-Iodo-phenyl)-2,6-dioxo-3-propyl-1,2,3,6-tetrahydropurine-7-car-
boxylic acid tert-Butyl Ester (4): A 50-mL round bottom flask
equipped with a stir bar was charged with 2 (398 mg, 1.35 mmol) and
CH.sub.2Cl.sub.2 (14 mL). The reaction mixture was treated at
25.degree. C. consecutively with boronic acid 3 (503 mg, 2.0 mmol),
Et.sub.3N (0.4 mL, 2.7 mmol), crushed 4 .ANG. mol. sieves (1.6 g,
4.times. weight), and Cu(OAc).sub.2 (487 mg, 2.7 mmol). After 3 h,
the reaction was filtered through a plug of Celite.RTM. and the
Celite.RTM. pad was washed with CH.sub.2Cl.sub.2 (100 mL). The
organic phase was washed with brine (50 mL), dried (MgSO.sub.4),
filtered, and concentrated in vacuo. Chromatography of the residue
on silica (20-30% EtOAc/hexanes) provided 4 (296 mg, 44%) as a
white solid: .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. 8.27 (s,
1H), 7.80 (d, J=8.4 Hz, 2H), 6.99 (d, J=8.4 Hz, 2H), 4.11 (t, J=7.3
Hz, 2H), 1.84-1.77 (m, 2H), 1.63 (s, 9H), 0.98 (t, J=7.4 Hz,
3H).
[0815]
1-(2'-Methylsulfanyl-biphenyl-4-yl)-(4-iodo-phenyl)-3-propyl-3,7-di-
hydro-purine-2,6-dione (6): A 25-mL round bottom flask equipped
with a stir bar and a reflux condenser was charged with aryl iodide
4 (296 mg, 0.60 mmol), DME (4.5 mL), 2 M Na.sub.2CO.sub.3 (1.5 mL),
and boronic acid 5 (121 mg, 0.72 mmol). A gentle stream of N.sub.2
was bubbled through the mixture for 30 min followed by the addition
of Pd(PPh.sub.3).sub.4 (30 mg, 5 mol %). The flask was evacuated
and purged with N.sub.2 (3.times.), and heated at 95.degree. C. for
72 h. The cooled solution was partitioned between H.sub.2O (25 mL)
and EtOAc (50 mL). The organic layer was washed with brine (25 mL),
dried (Na.sub.2SO.sub.4), filtered, and concentrated in vacuo.
Chromatography of the residue on silica (50-70% EtOAc/hexanes)
provided biaryl 6 (180 mg, 77%) as a white powder: APCI-MS m/z:
[C.sub.21H.sub.20N.sub.4O.sub.2S+H].sup.+393; .sup.1H NMR (300 MHz,
CDCl.sub.3) .delta. 9.27 (br s, 1H), 7.80-7.00 (m, 9H), 4.16-4.11
(m, 2H), 2.36 (s, 3H), 1.90-1.75 (m, 2H), 1.14 (t, J=7.2 Hz,
3H).
[0816]
3-[1-(2'-Methylsulfanyl-biphenyl-4-yl)-2,6-dioxo-3-propyl-1,2,3,6-t-
etrahydro-purine-7-yl]-benzonitrile (8): A 25-mL round bottom flask
equipped with a stir bar was charged with 6 (180 mg, 0.46 mmol) and
CH.sub.2Cl.sub.2 (5.0 mL). The reaction mixture was treated with
boronic acid 7 (135 mg, 0.92 mmol), Et.sub.3N (0.13 mL, 0.92 mmol),
crushed 4 A mol. sieves (720 mg, 4.times. weight) and Cu(OAc).sub.2
(167 mg, 0.92 mmol) at 25.degree. C. After 12 h, the reaction was
filtered through a plug of Celite.RTM. and washed with
CH.sub.2Cl.sub.2 (100 mL). The organic phase was washed with brine
(50 mL), dried (Na.sub.2SO.sub.4), filtered, and concentrated in
vacuo. Chromatography of the residue on silica (40-50%
EtOAc/hexanes) provided 8 (100 mg, 44%) as a white solid: ESI-MS
m/z: [C.sub.28H.sub.23N.sub.5O.sub.2S+H].sup.+ 494; .sup.1H NMR
(300 MHz, CDCl.sub.3) .delta. 7.90-7.00 (m, 13H), 4.19 (t, J=7.5
Hz, 2H) 2.33 (s, 3H), 1.99-1.85 (m, 2H), 1.03 (t, J=7.3 Hz,
3H).
[0817]
3-[1-(2'-Methylsulfonyl-biphenyl-4-yl)-2,6-dioxo-3-propyl-1,2,3,6-t-
etrahydro-purine-7-yl]-benzonitrile (9): A 10-mL round bottom flask
equipped with a stir bar was charged with 8 (47 mg, 0.09 mmol) and
CH.sub.2Cl.sub.2 (3.0 mL). The reaction mixture was treated with
K.sub.2CO.sub.3 (62 mg, 0.45 mmol) and m-CPBA (55 mg, 0.31 mmol,
3.5 equiv) at 25.degree. C. After 5 h, the reaction was
concentrated in vacuo. The residue was redissolved in EtOAc (20 mL)
and washed with H.sub.2O (10 mL). The aqueous phase was extracted
with EtOAc (3.times.10 mL) and the combined organic extracts were
washed consecutively with saturated Na.sub.2S.sub.2O.sub.3 (5 mL),
saturated NaHCO.sub.3 (5 mL), and brine (5 mL). The organic phase
was dried (Na.sub.2SO.sub.4), filtered, and concentrated in vacuo.
Chromatography of the residue on silica (50-70% EtOAc/hexane)
provided 9 (33 mg, 70%) as a white solid: ESI-MS m/z:
[C.sub.28H.sub.23N.sub.5O.sub.4S+H].sup.+526; .sup.1H NMR (300 MHz,
CDCl.sub.3) .delta. 7.90-7.00 (m, 13H), 4.19 (t, J=7.5 Hz, 2H) 2.33
(s, 3H), 1.99-1.85 (m, 2H), 1.03 (t, J=7.3 Hz, 3H).
[0818]
7-(3-Aminomethyl-phenyl)-1-(2'-methanesulfonyl-biphenyl-4-yl)-3-pro-
pyl-3,7-dihydro-purine-2,6 dione (10): A Parr bomb was charged with
9 (100 mg, 0.19 mmol), MeOH (10 mL), 1 N HCl (0.2 mL), and
catalytic amount of 10% Pd/C. The reaction mixture was exposed to
H.sub.2 at 38 psi. After 12 h, the reaction was filtered through a
pad of Celite.RTM. and concentrated in vacuo. The residue was
dissolved in CH.sub.2Cl.sub.2 (10 mL), washed with NaOH (5.0 mL,
30% aqueous), dried (Na.sub.2SO.sub.4), filtered, and concentrated
in vacuo. Chromatography of the residue on silica (8%
MeOH/CH.sub.2Cl.sub.2) provided free base 10 (35 mg, 35%) as a pale
yellow solid: ESI-MS m/z:
[C.sub.28H.sub.27N.sub.5O.sub.4S+H].sup.+5- 30; .sup.1H NMR (300
MHz, DMSO-d.sub.6) .delta. 8.42 (s, 1H), 8.12 (d, J=7.5 Hz, 1H),
7.82-7.35 (m, 10H), 4.06 (br t, 2H), 3.80 (s, 2H), 2.79 (s, 3H),
1.83-1.75 (m, 2H), 0.97 (t, J=7.4 Hz, 3H).
[0819] The following tables contain representative examples of the
present invention. Each entry in each table is intended to be
paired with each formulae at the start of the table. For example,
in Tables 1 and 2, example 1 is intended to be paired with each of
the formulae.
[0820] The following nomenclature is intended for group A in the
following tables. 40
1TABLE 1 41 42 43 44 45 46 47 48 49 50 51 52 53 54
[0821] G is selected from:
[0822] 4-(methoxy)phenyl;
[0823] 3-Cl-phenyl;
[0824] 4-F-3-Cl-phenyl;
[0825] 3-H.sub.2N-4-Cl-phenyl;
[0826] 2-(H.sub.2NCH.sub.2) phenyl;
[0827] 2-(H.sub.2NCH.sub.2)-3-F-phenyl;
[0828] 2-(H.sub.2NCH.sub.2)-4-F-phenyl;
[0829] 2-(H.sub.2NCH.sub.2)-5-F-phenyl;
[0830] 2-(H.sub.2NCH.sub.2)-6-F-phenyl;
[0831] 3-(amidino)phenyl;
[0832] 2-(H.sub.2NC(O))phenyl;
[0833] 3-(H.sub.2NC(O))phenyl;
[0834] 3-(H.sub.2NC(O))-4-methoxy-phenyl;
[0835] 4-Cl-pyridin-2-yl;
[0836] 3-amino-phthalazin-5-yl;
[0837] 3-amino-phthalazin-6-yl;
[0838] 1-aminoisoquinolin-7-yl;
[0839] 4-aminoquinazol-6-yl;
[0840] 3-aminobenzisoxazol-5-yl; and,
[0841] 3-aminoindazol-5-yl;
[0842] R.sup.1a is CH.sub.3;
[0843] Ex# A B
[0844] 1. phenyl 2-(NH.sub.2SO.sub.2)phenyl
[0845] 2. phenyl 2-(CH.sub.3SO.sub.2)phenyl
[0846] 3. phenyl 3-NH.sub.2SO.sub.2-4-pyridyl
[0847] 4. phenyl 3-CH.sub.3SO.sub.2-4-pyridyl
[0848] 5. phenyl 2-(CH.sub.3NH)phenyl
[0849] 6. phenyl 3-((CH.sub.3).sub.2NCH.sub.2)-4-pyridyl
[0850] 7. phenyl 2-(N-(3-R--HO-pyrrolidinyl)CH.sub.2)phenyl
[0851] 8. phenyl 2-(N-(4-HO-piperidinyl) CH.sub.2) phenyl
[0852] 9. phenyl 2-((CH.sub.3).sub.2NCH.sub.2)phenyl
[0853] 10. phenyl 2-((CH.sub.3)NHCH.sub.2)phenyl
[0854] 11. phenyl 2-((CH.sub.3CH.sub.2) NHCH.sub.2) phenyl
[0855] 12. phenyl 2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)phenyl
[0856] 13. phenyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)phenyl
[0857] 14. phenyl 2-(((CH.sub.3).sub.2CH)NHCH.sub.2)phenyl
[0858] 15. phenyl 2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)phenyl
[0859] 16. phenyl 2-((cyclopropyl) NHCH.sub.2) phenyl
[0860] 17. phenyl 2-((cyclopropyl).sub.2NCH.sub.2) phenyl
[0861] 18. phenyl 2-((cyclobutyl) NHCH.sub.2) phenyl
[0862] 19. phenyl 2-((cyclobutyl).sub.2NCH.sub.2)phenyl
[0863] 20. phenyl 2-((cyclopentyl)NHCH.sub.2)phenyl
[0864] 21. phenyl 2-((cyclopentyl).sub.2NCH.sub.2) phenyl
[0865] 22. phenyl 2-((cyclohexyl) NHCH.sub.2) phenyl
[0866] 23. phenyl 2-((cyclohexyl).sub.2NCH.sub.2) phenyl
[0867] 24. phenyl 1-CH.sub.3-2-imidazolyl
[0868] 25. phenyl 2-CH.sub.3-1-imidazolyl
[0869] 26. phenyl 2-((CH.sub.3).sub.2NCH.sub.2)-1-imidazolyl
[0870] 27. phenyl 2-((CH.sub.3)NHCH.sub.2)-1-imidazolyl
[0871] 28. phenyl 2-((CH.sub.3CH.sub.2)NHCH.sub.2)-1-imidazolyl
[0872] 29. phenyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)-1-imidazolyl
[0873] 30. phenyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)-1-imidazolyl
[0874] 31. phenyl
2-(((CH.sub.3).sub.2CH)NHCH.sub.2)-1-imidazolyl
[0875] 32. phenyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)-1-imidazolyl
[0876] 33. phenyl 2-((cyclopropyl)NHCH.sub.2)-1-imidazolyl
[0877] 34. phenyl 2-((cyclopropyl).sub.2NCH.sub.2)-1-imidazolyl
[0878] 35. phenyl 2-((cyclobutyl)NHCH.sub.2)-1-imidazolyl
[0879] 36. phenyl 2-((cyclobutyl).sub.2NCH.sub.2)-1-imidazolyl
[0880] 37. phenyl 2-((cyclopentyl)NHCH.sub.2)-1-imidazolyl
[0881] 38. phenyl 2-((cyclopentyl).sub.2NCH.sub.2)-1-imidazolyl
[0882] 39. phenyl 2-((cyclohexyl)NHCH.sub.2)-1-imidazolyl
[0883] 40. phenyl 2-((cyclohexyl).sub.2NCH.sub.2)-1-imidazolyl
[0884] 41. 2-pyridyl 2-(NH.sub.2SO.sub.2)phenyl
[0885] 42. 2-pyridyl 2-(CH.sub.3SO.sub.2)phenyl
[0886] 43. 2-pyridyl 3-NH.sub.2SO.sub.2-4-pyridyl
[0887] 44. 2-pyridyl 3-CH.sub.3SO.sub.2-4-pyridyl
[0888] 45. 2-pyridyl 2-(CH.sub.3NH)phenyl
[0889] 46. 2-pyridyl 3-((CH.sub.3).sub.2NCH.sub.2)-4-pyridyl
[0890] 47. 2-pyridyl 2-(N-(3-R--HO-pyrrolidinyl)CH.sub.2)phenyl
[0891] 48. 2-pyridyl 2-(N-(4-HO-piperidinyl)CH.sub.2)phenyl
[0892] 49. 2-pyridyl 2-((CH.sub.3).sub.2NCH.sub.2)phenyl
[0893] 50. 2-pyridyl 2-((CH.sub.3)NHCH.sub.2)phenyl
[0894] 51. 2-pyridyl 2-((CH.sub.3CH.sub.2)NHCH.sub.2)phenyl
[0895] 52. 2-pyridyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)phenyl
[0896] 53. 2-pyridyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)phenyl
[0897] 54. 2-pyridyl 2-(((CH.sub.3).sub.2CH)NHCH.sub.2)phenyl
[0898] 55. 2-pyridyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)phenyl
[0899] 56. 2-pyridyl 2-((cyclopropyl)NHCH.sub.2)phenyl
[0900] 57. 2-pyridyl 2-((cyclopropyl).sub.2NCH.sub.2)phenyl
[0901] 58. 2-pyridyl 2-((cyclobutyl)NHCH.sub.2)phenyl
[0902] 59. 2-pyridyl 2-((cyclobutyl).sub.2NCH.sub.2)phenyl
[0903] 60. 2-pyridyl 2-((cyclopentyl)NHCH.sub.2)phenyl
[0904] 61. 2-pyridyl 2-((cyclopentyl).sub.2NCH.sub.2)phenyl
[0905] 62. 2-pyridyl 2-((cyclohexyl) NHCH.sub.2)phenyl
[0906] 63. 2-pyridyl 2-((cyclohexyl).sub.2NCH.sub.2)phenyl
[0907] 64. 2-pyridyl 1-CH.sub.3-2-imidazolyl
[0908] 65. 2-pyridyl 2-CH.sub.3-1-imidazolyl
[0909] 66. 2-pyridyl 2-((CH.sub.3).sub.2NCH.sub.2)-1-imidazolyl
[0910] 67. 2-pyridyl 2-((CH.sub.3)NHCH.sub.2)-1-imidazolyl
[0911] 68. 2-pyridyl
2-((CH.sub.3CH.sub.2)NHCH.sub.2)-1-imidazolyl
[0912] 69. 2-pyridyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)-1-imidazolyl
[0913] 70. 2-pyridyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)-1-imidazoly- l
[0914] 71. 2-pyridyl
2-(((CH.sub.3).sub.2CH)NHCH.sub.2)-1-imidazolyl
[0915] 72. 2-pyridyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)-1-imidazolyl
[0916] 73. 2-pyridyl 2-((cyclopropyl)NHCH.sub.2)-1-imidazolyl
[0917] 74. 2-pyridyl
2-((cyclopropyl).sub.2NCH.sub.2)-1-imidazolyl
[0918] 75. 2-pyridyl 2-((cyclobutyl)NHCH.sub.2)-1-imidazolyl
[0919] 76. 2-pyridyl
2-((cyclobutyl).sub.2NCH.sub.2)-1-imidazolyl
[0920] 77. 2-pyridyl 2-((cyclopentyl)NHCH.sub.2)-1-imidazolyl
[0921] 78. 2-pyridyl
2-((cyclopentyl).sub.2NCH.sub.2)-1-imidazolyl
[0922] 79. 2-pyridyl 2-((cyclohexyl)NHCH.sub.2)-1-imidazolyl
[0923] 80. 2-pyridyl
2-((cyclohexyl).sub.2NCH.sub.2)-1-imidazolyl
[0924] 81. 3-pyridyl 2-(NH.sub.2SO.sub.2)phenyl
[0925] 82. 3-pyridyl 2-(CH.sub.3SO.sub.2)phenyl
[0926] 83. 3-pyridyl 3-NH.sub.2SO.sub.2-4-pyridyl
[0927] 84. 3-pyridyl 3-CH.sub.3SO.sub.2-4-pyridyl
[0928] 85. 3-pyridyl 2-(CH.sub.3NH)phenyl
[0929] 86. 3-pyridyl 3-((CH.sub.3).sub.2NCH.sub.2)-4-pyridyl
[0930] 87. 3-pyridyl 2-(N-(3-R--HO-pyrrolidinyl)CH.sub.2)phenyl
[0931] 88. 3-pyridyl 2-(N-(4-HO-piperidinyl)CH.sub.2)phenyl
[0932] 89. 3-pyridyl 2-((CH.sub.3).sub.2NCH.sub.2)phenyl
[0933] 90. 3-pyridyl 2-((CH.sub.3)NHCH.sub.2)phenyl
[0934] 91. 3-pyridyl 2-((CH.sub.3CH.sub.2)NHCH.sub.2)phenyl
[0935] 92. 3-pyridyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)phenyl
[0936] 93. 3-pyridyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)phenyl
[0937] 94. 3-pyridyl 2-(((CH.sub.3).sub.2CH)NHCH.sub.2)phenyl
[0938] 95. 3-pyridyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)phenyl
[0939] 96. 3-pyridyl 2-((cyclopropyl)NHCH.sub.2)phenyl
[0940] 97. 3-pyridyl 2-((cyclopropyl).sub.2NCH.sub.2)phenyl
[0941] 98. 3-pyridyl 2-((cyclobutyl)NHCH.sub.2)phenyl
[0942] 99. 3-pyridyl 2-((cyclobutyl).sub.2NCH.sub.2) phenyl
[0943] 100. 3-pyridyl 2-((cyclopentyl)NHCH.sub.2)phenyl
[0944] 101. 3-pyridyl 2-((cyclopentyl).sub.2NCH.sub.2)phenyl
[0945] 102. 3-pyridyl 2-((cyclohexyl)NHCH.sub.2)phenyl
[0946] 103. 3-pyridyl 2-((cyclohexyl).sub.2NCH.sub.2)phenyl
[0947] 104. 3-pyridyl 1-CH.sub.3-2-imidazolyl
[0948] 105. 3-pyridyl 2-CH.sub.3-1-imidazolyl
[0949] 106. 3-pyridyl
2-((CH.sub.3).sub.2NCH.sub.2)-1-imidazolyl
[0950] 107. 3-pyridyl 2-((CH.sub.3)NHCH.sub.2)-1-imidazolyl
[0951] 108. 3-pyridyl
2-((CH.sub.3CH.sub.2)NHCH.sub.2)-1-imidazolyl
[0952] 109. 3-pyridyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)-1-imidazolyl
[0953] 110. 3-pyridyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)-1-imidazol- yl
[0954] 111. 3-pyridyl
2-(((CH.sub.3).sub.2CH)NHCH.sub.2)-1-imidazolyl
[0955] 112. 3-pyridyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)-1-imidazolyl
[0956] 113. 3-pyridyl 2-((cyclopropyl)NHCH.sub.2)-1-imidazolyl
[0957] 114. 3-pyridyl
2-((cyclopropyl).sub.2NCH.sub.2)-1-imidazolyl
[0958] 115. 3-pyridyl 2-((cyclobutyl)NHCH.sub.2)-1-imidazolyl
[0959] 116. 3-pyridyl
2-((cyclobutyl).sub.2NCH.sub.2)-1-imidazolyl
[0960] 117. 3-pyridyl 2-((cyclopentyl)NHCH.sub.2)-1-imidazolyl
[0961] 118. 3-pyridyl
2-((cyclopentyl).sub.2NCH.sub.2)-1-imidazolyl
[0962] 119. 3-pyridyl 2-((cyclohexyl)NHCH.sub.2)-1-imidazolyl
[0963] 120. 3-pyridyl
2-((cyclohexyl).sub.2NCH.sub.2)-1-imidazolyl
[0964] 121. 2-pyrimidyl 2-(NH.sub.2SO.sub.2)phenyl
[0965] 122. 2-pyrimidyl 2-(CH.sub.3SO.sub.2)phenyl
[0966] 123. 2-pyrimidyl 3-NH.sub.2SO.sub.2-4-pyridyl
[0967] 124. 2-pyrimidyl 3-CH.sub.3SO.sub.2-4-pyridyl
[0968] 125. 2-pyrimidyl 2-(CH.sub.3NH)phenyl
[0969] 126. 2-pyrimidyl 3-((CH.sub.3).sub.2NCH.sub.2)-4-pyridyl
[0970] 127. 2-pyrimidyl
2-(N-(3-R--HO-pyrrolidinyl)CH.sub.2)phenyl
[0971] 128. 2-pyrimidyl 2-(N-(4-HO-piperidinyl)CH.sub.2)phenyl
[0972] 129. 2-pyrimidyl 2-((CH.sub.3).sub.2NCH.sub.2)phenyl
[0973] 130. 2-pyrimidyl 2-((CH.sub.3)NHCH.sub.2)phenyl
[0974] 131. 2-pyrimidyl 2-((CH.sub.3CH.sub.2)NHCH.sub.2)phenyl
[0975] 132. 2-pyrimidyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)phenyl
[0976] 133. 2-pyrimidyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)phenyl
[0977] 134. 2-pyrimidyl
2-(((CH.sub.3).sub.2CH)NHCH.sub.2)phenyl
[0978] 135. 2-pyrimidyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)phenyl
[0979] 136. 2-pyrimidyl 2-((cyclopropyl)NHCH.sub.2) phenyl
[0980] 137. 2-pyrimidyl 2-((cyclopropyl).sub.2NCH.sub.2)phenyl
[0981] 138. 2-pyrimidyl 2-((cyclobutyl) NHCH.sub.2) phenyl
[0982] 139. 2-pyrimidyl 2-((cyclobutyl).sub.2NCH.sub.2)phenyl
[0983] 140. 2-pyrimidyl 2-((cyclopentyl)NHCH.sub.2)phenyl
[0984] 141. 2-pyrimidyl 2-((cyclopentyl).sub.2NCH.sub.2) phenyl
[0985] 142. 2-pyrimidyl 2-((cyclohexyl)NHCH.sub.2)phenyl
[0986] 143. 2-pyrimidyl 2-((cyclohexyl).sub.2NCH.sub.2)phenyl
[0987] 144. 2-pyrimidyl 1-CH.sub.3-2-imidazolyl
[0988] 145. 2-pyrimidyl 2-CH.sub.3-1-imidazolyl
[0989] 146. 2-pyrimidyl
2-((CH.sub.3).sub.2NCH.sub.2)-1-imidazolyl
[0990] 147. 2-pyrimidyl 2-((CH.sub.3)NHCH.sub.2)-1-imidazolyl
[0991] 148. 2-pyrimidyl
2-((CH.sub.3CH.sub.2)NHCH.sub.2)-1-imidazolyl
[0992] 149. 2-pyrimidyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)-1-imidazolyl
[0993] 150. 2-pyrimidyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)-1-imidaz- olyl
[0994] 151. 2-pyrimidyl
2-(((CH.sub.3).sub.2CH)NHCH.sub.2)-1-imidazolyl
[0995] 152. 2-pyrimidyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)-1-imidazol- yl
[0996] 153. 2-pyrimidyl
2-((cyclopropyl)NHCH.sub.2)-1-imidazolyl
[0997] 154. 2-pyrimidyl
2-((cyclopropyl).sub.2NCH.sub.2)-1-imidazolyl
[0998] 155. 2-pyrimidyl 2-((cyclobutyl)NHCH.sub.2)-1-imidazolyl
[0999] 156. 2-pyrimidyl
2-((cyclobutyl).sub.2NCH.sub.2)-1-imidazolyl
[1000] 157. 2-pyrimidyl
2-((cyclopentyl)NHCH.sub.2)-1-imidazolyl
[1001] 158. 2-pyrimidyl
2-((cyclopentyl).sub.2NCH.sub.2)-1-imidazolyl
[1002] 159. 2-pyrimidyl 2-((cyclohexyl)NHCH.sub.2)-1-imidazolyl
[1003] 160. 2-pyrimidyl
2-((cyclohexyl).sub.2NCH.sub.2)-1-imidazolyl
[1004] 161. 5-pyrimidyl 2-(NH.sub.2SO.sub.2)phenyl
[1005] 162. 5-pyrimidyl 2-(CH.sub.3SO.sub.2)phenyl
[1006] 163. 5-pyrimidyl 3-NH.sub.2SO.sub.2-4-pyridyl
[1007] 164. 5-pyrimidyl 3-CH.sub.3SO.sub.2-4-pyridyl
[1008] 165. 5-pyrimidyl 2-(CH.sub.3NH)phenyl
[1009] 166. 5-pyrimidyl 3-((CH.sub.3).sub.2NCH.sub.2)-4-pyridyl
[1010] 167. 5-pyrimidyl
2-(N-(3-R--HO-pyrrolidinyl)CH.sub.2)phenyl
[1011] 168. 5-pyrimidyl 2-(N-(4-HO-piperidinyl)CH.sub.2)phenyl
[1012] 169. 5-pyrimidyl 2-((CH.sub.3).sub.2NCH.sub.2)phenyl
[1013] 170. 5-pyrimidyl 2-((CH.sub.3)NHCH.sub.2)phenyl
[1014] 171. 5-pyrimidyl 2-((CH.sub.3CH.sub.2)NHCH.sub.2)phenyl
[1015] 172. 5-pyrimidyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)phenyl
[1016] 173. 5-pyrimidyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)phenyl
[1017] 174. 5-pyrimidyl
2-(((CH.sub.3).sub.2CH)NHCH.sub.2)phenyl
[1018] 175. 5-pyrimidyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)phenyl
[1019] 176. 5-pyrimidyl 2-((cyclopropyl)NHCH.sub.2)phenyl
[1020] 177. 5-pyrimidyl 2-((cyclopropyl).sub.2NCH.sub.2)phenyl
[1021] 178. 5-pyrimidyl 2-((cyclobutyl)NHCH.sub.2)phenyl
[1022] 179. 5-pyrimidyl 2-((cyclobutyl).sub.2NCH.sub.2)phenyl
[1023] 180. 5-pyrimidyl 2-((cyclopentyl) NHCH.sub.2) phenyl
[1024] 181. 5-pyrimidyl 2-((cyclopentyl).sub.2NCH.sub.2)phenyl
[1025] 182. 5-pyrimidyl 2-((cyclohexyl)NHCH.sub.2)phenyl
[1026] 183. 5-pyrimidyl 2-((cyclohexyl).sub.2NCH.sub.2)phenyl
[1027] 184. 5-pyrimidyl 1-CH.sub.3-2-imidazolyl
[1028] 185. 5-pyrimidyl 2-CH.sub.3-1-imidazolyl
[1029] 186. 5-pyrimidyl
2-((CH.sub.3).sub.2NCH.sub.2)-1-imidazolyl
[1030] 187. 5-pyrimidyl 2-((CH.sub.3)NHCH.sub.2)-1-imidazolyl
[1031] 188. 5-pyrimidyl
2-((CH.sub.3CH.sub.2)NHCH.sub.2)-1-imidazolyl
[1032] 189. 5-pyrimidyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)-1-imidazolyl
[1033] 190. 5-pyrimidyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)-1-imidaz- olyl
[1034] 191. 5-pyrimidyl
2-(((CH.sub.3).sub.2CH)NHCH.sub.2)-1-imidazolyl
[1035] 192. 5-pyrimidyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)-1-imidazol- yl
[1036] 193. 5-pyrimidyl
2-((cyclopropyl)NHCH.sub.2)-1-imidazolyl
[1037] 194. 5-pyrimidyl
2-((cyclopropyl).sub.2NCH.sub.2)-1-imidazolyl
[1038] 195. 5-pyrimidyl 2-((cyclobutyl)NHCH.sub.2)-1-imidazolyl
[1039] 196. 5-pyrimidyl
2-((cyclobutyl).sub.2NCH.sub.2)-1-imidazolyl
[1040] 197. 5-pyrimidyl
2-((cyclopentyl)NHCH.sub.2)-1-imidazolyl
[1041] 198. 5-pyrimidyl
2-((cyclopentyl).sub.2NCH.sub.2)-1-imidazolyl
[1042] 199. 5-pyrimidyl 2-((cyclohexyl)NHCH.sub.2)-1-imidazolyl
[1043] 200. 5-pyrimidyl
2-((cyclohexyl).sub.2NCH.sub.2)-1-imidazolyl
[1044] 201. 2-Cl-phenyl 2-(NH.sub.2SO.sub.2)phenyl
[1045] 202. 2-Cl-phenyl 2-(CH.sub.3SO.sub.2)phenyl
[1046] 203. 2-Cl-phenyl 3-NH.sub.2SO.sub.2-4-pyridyl
[1047] 204. 2-Cl-phenyl 3-CH.sub.3SO.sub.2-4-pyridyl
[1048] 205. 2-Cl-phenyl 2-(CH.sub.3NH)phenyl
[1049] 206. 2-Cl-phenyl 3-((CH.sub.3).sub.2NCH.sub.2)-4-pyridyl
[1050] 207. 2-Cl-phenyl
2-(N-(3-R--HO-pyrrolidinyl)CH.sub.2)phenyl
[1051] 208. 2-Cl-phenyl 2-(N-(4-HO-piperidinyl)CH.sub.2)phenyl
[1052] 209. 2-Cl-phenyl 2-((CH.sub.3).sub.2NCH.sub.2)phenyl
[1053] 210. 2-Cl-phenyl 2-((CH.sub.3)NHCH.sub.2)phenyl
[1054] 211. 2-Cl-phenyl 2-((CH.sub.3CH.sub.2)NHCH.sub.2)phenyl
[1055] 212. 2-Cl-phenyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)phenyl
[1056] 213. 2-Cl-phenyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)phenyl
[1057] 214. 2-Cl-phenyl
2-(((CH.sub.3).sub.2CH)NHCH.sub.2)phenyl
[1058] 215. 2-Cl-phenyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)phenyl
[1059] 216. 2-Cl-phenyl 2-((cyclopropyl)NHCH.sub.2)phenyl
[1060] 217. 2-Cl-phenyl 2-((cyclopropyl).sub.2NCH.sub.2)phenyl
[1061] 218. 2-Cl-phenyl 2-((cyclobutyl)NHCH.sub.2)phenyl
[1062] 219. 2-Cl-phenyl 2-((cyclobutyl).sub.2NCH.sub.2)phenyl
[1063] 220. 2-Cl-phenyl 2-((cyclopentyl)NHCH.sub.2)phenyl
[1064] 221. 2-Cl-phenyl 2-((cyclopentyl).sub.2NCH.sub.2)phenyl
[1065] 222. 2-Cl-phenyl 2-((cyclohexyl)NHCH.sub.2)phenyl
[1066] 223. 2-Cl-phenyl 2-((cyclohexyl).sub.2NCH.sub.2)phenyl
[1067] 224. 2-Cl-phenyl 1-CH.sub.3-2-imidazolyl
[1068] 225. 2-Cl-phenyl 2-CH.sub.3-1-imidazolyl
[1069] 226. 2-Cl-phenyl
2-((CH.sub.3).sub.2NCH.sub.2)-1-imidazolyl
[1070] 227. 2-Cl-phenyl 2-((CH.sub.3)NHCH.sub.2)-1-imidazolyl
[1071] 228. 2-Cl-phenyl
2-((CH.sub.3CH.sub.2)NHCH.sub.2)-1-imidazolyl
[1072] 229. 2-Cl-phenyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)-1-imidazolyl
[1073] 230. 2-Cl-phenyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)-1-imidaz- olyl
[1074] 231. 2-Cl-phenyl
2-(((CH.sub.3).sub.2CH)NHCH.sub.2)-1-imidazolyl
[1075] 232. 2-Cl-phenyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)-1-imidazol- yl
[1076] 233. 2-Cl-phenyl
2-((cyclopropyl)NHCH.sub.2)-1-imidazolyl
[1077] 234. 2-Cl-phenyl
2-((cyclopropyl).sub.2NCH.sub.2)-1-imidazolyl
[1078] 235. 2-Cl-phenyl 2-((cyclobutyl)NHCH.sub.2)-1-imidazolyl
[1079] 236. 2-Cl-phenyl
2-((cyclobutyl).sub.2NCH.sub.2)-1-imidazolyl
[1080] 237. 2-Cl-phenyl
2-((cyclopentyl)NHCH.sub.2)-1-imidazolyl
[1081] 238. 2-Cl-phenyl
2-((cyclopentyl).sub.2NCH.sub.2)-1-imidazolyl
[1082] 239. 2-Cl-phenyl 2-((cyclohexyl)NHCH.sub.2)-1-imidazolyl
[1083] 240. 2-Cl-phenyl
2-((cyclohexyl).sub.2NCH.sub.2)-1-imidazolyl
[1084] 241. 2-F-phenyl 2-(NH.sub.2SO.sub.2)phenyl
[1085] 242. 2-F-phenyl 2-(CH.sub.3SO.sub.2)phenyl
[1086] 243. 2-F-phenyl 3-NH.sub.2SO.sub.2-4-pyridyl
[1087] 244. 2-F-phenyl 3-CH.sub.3SO.sub.2-4-pyridyl
[1088] 245. 2-F-phenyl 2-(CH.sub.3NH)phenyl
[1089] 246. 2-F-phenyl 3-((CH.sub.3).sub.2NCH.sub.2)-4-pyridyl
[1090] 247. 2-F-phenyl
2-(N-(3-R--HO-pyrrolidinyl)CH.sub.2)phenyl
[1091] 248. 2-F-phenyl 2-(N-(4-HO-piperidinyl)CH.sub.2)phenyl
[1092] 249. 2-F-phenyl 2-((CH.sub.3).sub.2NCH.sub.2)phenyl
[1093] 250. 2-F-phenyl 2-((CH.sub.3)NHCH.sub.2)phenyl
[1094] 251. 2-F-phenyl 2-((CH.sub.3CH.sub.2)NHCH.sub.2)phenyl
[1095] 252. 2-F-phenyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)phenyl
[1096] 253. 2-F-phenyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)phenyl
[1097] 254. 2-F-phenyl 2-(((CH.sub.3).sub.2CH)NHCH.sub.2)phenyl
[1098] 255. 2-F-phenyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)phenyl
[1099] 256. 2-F-phenyl 2-((cyclopropyl)NHCH.sub.2)phenyl
[1100] 257. 2-F-phenyl 2-((cyclopropyl).sub.2NCH.sub.2)phenyl
[1101] 258. 2-F-phenyl 2-((cyclobutyl)NHCH.sub.2)phenyl
[1102] 259. 2-F-phenyl 2-((cyclobutyl).sub.2NCH.sub.2)phenyl
[1103] 260. 2-F-phenyl 2-((cyclopentyl)NHCH.sub.2)phenyl
[1104] 261. 2-F-phenyl 2-((cyclopentyl).sub.2NCH.sub.2)phenyl
[1105] 262. 2-F-phenyl 2-((cyclohexyl)NHCH.sub.2)phenyl
[1106] 263. 2-F-phenyl 2-((cyclohexyl).sub.2NCH.sub.2)phenyl
[1107] 264. 2-F-phenyl 1-CH.sub.3-2-imidazolyl
[1108] 265. 2-F-phenyl 2-CH.sub.3-1-imidazolyl
[1109] 266. 2-F-phenyl
2-((CH.sub.3).sub.2NCH.sub.2)-1-imidazolyl
[1110] 267. 2-F-phenyl 2-((CH.sub.3)NHCH.sub.2)-1-imidazolyl
[1111] 268. 2-F-phenyl
2-((CH.sub.3CH.sub.2)NHCH.sub.2)-1-imidazolyl
[1112] 269. 2-F-phenyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)-1-imidazolyl
[1113] 270. 2-F-phenyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)-1-imidazo- lyl
[1114] 271. 2-F-phenyl
2-(((CH.sub.3).sub.2CH)NHCH.sub.2)-1-imidazolyl
[1115] 272. 2-F-phenyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)-1-imidazoly- l
[1116] 273. 2-F-phenyl 2-((cyclopropyl)NHCH.sub.2)-1-imidazolyl
[1117] 274. 2-F-phenyl
2-((cyclopropyl).sub.2NCH.sub.2)-1-imidazolyl
[1118] 275. 2-F-phenyl 2-((cyclobutyl)NHCH.sub.2)-1-imidazolyl
[1119] 276. 2-F-phenyl
2-((cyclobutyl).sub.2NCH.sub.2)-1-imidazolyl
[1120] 277. 2-F-phenyl 2-((cyclopentyl)NHCH.sub.2)-1-imidazolyl
[1121] 278. 2-F-phenyl
2-((cyclopentyl).sub.2NCH.sub.2)-1-imidazolyl
[1122] 279. 2-F-phenyl 2-((cyclohexyl)NHCH.sub.2)-1-imidazolyl
[1123] 280. 2-F-phenyl
2-((cyclohexyl).sub.2NCH.sub.2)-1-imidazolyl
[1124] 281. 2,6-diF-phenyl 2-(NH.sub.2SO.sub.2)phenyl
[1125] 282. 2,6-diF-phenyl 2-(CH.sub.3SO.sub.2)phenyl
[1126] 283. 2,6-diF-phenyl 3-NH.sub.2SO.sub.2-4-pyridyl
[1127] 284. 2,6-diF-phenyl 3-CH.sub.3SO.sub.2-4-pyridyl
[1128] 285. 2,6-diF-phenyl 2-(CH.sub.3NH)phenyl
[1129] 286. 2,6-diF-phenyl
3-((CH.sub.3).sub.2NCH.sub.2)-4-pyridyl
[1130] 287. 2,6-diF-phenyl
2-(N-(3-R--HO-pyrrolidinyl)CH.sub.2)phenyl
[1131] 288. 2,6-diF-phenyl
2-(N-(4-HO-piperidinyl)CH.sub.2)phenyl
[1132] 289. 2,6-diF-phenyl 2-((CH.sub.3).sub.2NCH.sub.2)phenyl
[1133] 290. 2,6-diF-phenyl 2-((CH.sub.3)NHCH.sub.2)phenyl
[1134] 291. 2,6-diF-phenyl
2-((CH.sub.3CH.sub.2)NHCH.sub.2)phenyl
[1135] 292. 2,6-diF-phenyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)phenyl
[1136] 293. 2,6-diF-phenyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)phenyl
[1137] 294. 2,6-diF-phenyl
2-(((CH.sub.3).sub.2CH)NHCH.sub.2)phenyl
[1138] 295. 2,6-diF-phenyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)phenyl
[1139] 296. 2,6-diF-phenyl 2-((cyclopropyl)NHCH.sub.2)phenyl
[1140] 297. 2,6-diF-phenyl
2-((cyclopropyl).sub.2NCH.sub.2)phenyl
[1141] 298. 2,6-diF-phenyl 2-((cyclobutyl)NHCH.sub.2)phenyl
[1142] 299. 2,6-diF-phenyl
2-((cyclobutyl).sub.2NCH.sub.2)phenyl
[1143] 300. 2,6-diF-phenyl 2-((cyclopentyl)NHCH.sub.2)phenyl
[1144] 301. 2,6-diF-phenyl
2-((cyclopentyl).sub.2NCH.sub.2)phenyl
[1145] 302. 2,6-diF-phenyl 2-((cyclohexyl)NHCH.sub.2)phenyl
[1146] 303. 2,6-diF-phenyl
2-((cyclohexyl).sub.2NCH.sub.2)phenyl
[1147] 304. 2,6-diF-phenyl 1-CH.sub.3-2-imidazolyl
[1148] 305. 2,6-diF-phenyl 2-CH.sub.3-1-imidazolyl
[1149] 306. 2,6-diF-phenyl
2-((CH.sub.3).sub.2NCH.sub.2)-1-imidazolyl
[1150] 307. 2,6-diF-phenyl
2-((CH.sub.3)NHCH.sub.2)-1-imidazolyl
[1151] 308. 2,6-diF-phenyl
2-((CH.sub.3CH.sub.2)NHCH.sub.2)-1-imidazolyl
[1152] 309. 2,6-diF-phenyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)-1-imidazo- lyl
[1153] 310. 2,6-diF-phenyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)-1-imi- dazolyl
[1154] 311. 2,6-diF-phenyl
2-(((CH.sub.3).sub.2CH)NHCH.sub.2)-1-imidazolyl
[1155] 312. 2,6-diF-phenyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)-1-imida- zolyl
[1156] 313. 2,6-diF-phenyl
2-((cyclopropyl)NHCH.sub.2)-1-imidazolyl
[1157] 314. 2,6-diF-phenyl
2-((cyclopropyl).sub.2NCH.sub.2)-1-imidazolyl
[1158] 315. 2,6-diF-phenyl
2-((cyclobutyl)NHCH.sub.2)-1-imidazolyl
[1159] 316. 2,6-diF-phenyl
2-((cyclobutyl).sub.2NCH.sub.2)-1-imidazolyl
[1160] 317. 2,6-diF-phenyl
2-((cyclopentyl)NHCH.sub.2)-1-imidazolyl
[1161] 318. 2,6-diF-phenyl
2-((cyclopentyl).sub.2NCH.sub.2)-1-imidazolyl
[1162] 319. 2,6-diF-phenyl
2-((cyclohexyl)NHCH.sub.2)-1-imidazolyl
[1163] 320. 2,6-diF-phenyl
2-((cyclohexyl).sub.2NCH.sub.2)-1-imidazolyl
[1164] 321. piperidinyl 2-(NH.sub.2SO.sub.2)phenyl
[1165] 322. piperidinyl 2-(CH.sub.3SO.sub.2)phenyl
[1166] 323. piperidinyl 3-NH.sub.2SO.sub.2-4-pyridyl
[1167] 324. piperidinyl 3-CH.sub.3SO.sub.2-4-pyridyl
[1168] 325. piperidinyl 2-(CH.sub.3NH)phenyl
[1169] 326. piperidinyl 3-((CH.sub.3).sub.2NCH.sub.2)-4-pyridyl
[1170] 327. piperidinyl
2-(N-(3-R--HO-pyrrolidinyl)CH.sub.2)phenyl
[1171] 328. piperidinyl 2-(N-(4-HO-piperidinyl)CH.sub.2)phenyl
[1172] 329. piperidinyl 2-((CH.sub.3).sub.2NCH.sub.2)phenyl
[1173] 330. piperidinyl 2-((CH.sub.3)NHCH.sub.2)phenyl
[1174] 331. piperidinyl 2-((CH.sub.3CH.sub.2)NHCH.sub.2) phenyl
[1175] 332. piperidinyl 2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)
phenyl
[1176] 333. piperidinyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)phenyl
[1177] 334. piperidinyl
2-(((CH.sub.3).sub.2CH)NHCH.sub.2)phenyl
[1178] 335. piperidinyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)phenyl
[1179] 336. piperidinyl 2-((cyclopropyl) NHCH.sub.2) phenyl
[1180] 337. piperidinyl 2-((cyclopropyl).sub.2NCH.sub.2)phenyl
[1181] 338. piperidinyl 2-((cyclobutyl) NHCH.sub.2) phenyl
[1182] 339. piperidinyl 2-((cyclobutyl).sub.2NCH.sub.2)phenyl
[1183] 340. piperidinyl 2-((cyclopentyl) NHCH.sub.2) phenyl
[1184] 341. piperidinyl 2-((cyclopentyl).sub.2NCH.sub.2)phenyl
[1185] 342. piperidinyl 2-((cyclohexyl)NHCH.sub.2)phenyl
[1186] 343. piperidinyl 2-((cyclohexyl).sub.2NCH.sub.2)phenyl
[1187] 344. piperidinyl 1-CH.sub.3-2-imidazolyl
[1188] 345. piperidinyl 2-CH.sub.3-1-imidazolyl
[1189] 346. piperidinyl
2-((CH.sub.3).sub.2NCH.sub.2)-1-imidazolyl
[1190] 347. piperidinyl 2-((CH.sub.3)NHCH.sub.2)-1-imidazolyl
[1191] 348. piperidinyl
2-((CH.sub.3CH.sub.2)NHCH.sub.2)-1-imidazolyl
[1192] 349. piperidinyl
2-((CH.sub.3CH.sub.2).sub.2NCH.sub.2)-1-imidazolyl
[1193] 350. piperidinyl
2-((CH.sub.3CH.sub.2)N(CH.sub.3)CH.sub.2)-1-imidaz- olyl
[1194] 351. piperidinyl
2-(((CH.sub.3).sub.2CH)NHCH.sub.2)-1-imidazolyl
[1195] 352. piperidinyl
2-(((CH.sub.3).sub.2CH).sub.2NCH.sub.2)-1-imidazol- yl
[1196] 353. piperidinyl
2-((cyclopropyl)NHCH.sub.2)-1-imidazolyl
[1197] 354. piperidinyl
2-((cyclopropyl).sub.2NCH.sub.2)-1-imidazolyl
[1198] 355. piperidinyl 2-((cyclobutyl)NHCH.sub.2)-1-imidazolyl
[1199] 356. piperidinyl
2-((cyclobutyl).sub.2NCH.sub.2)-1-imidazolyl
[1200] 357. piperidinyl
2-((cyclopentyl)NHCH.sub.2)-1-imidazolyl
[1201] 358. piperidinyl
2-((cyclopentyl).sub.2NCH.sub.2)-1-imidazolyl
[1202] 359. piperidinyl 2-((cyclohexyl)NHCH.sub.2)-1-imidazolyl
[1203] 360. piperidinyl
2-((cyclohexyl).sub.2NCH.sub.2)-1-imidazolyl
[1204] 361. piperidinyl isopropyl
2 TABLE 2 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is CH.sub.2CH.sub.3.
[1205]
3 TABLE 3 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is CF.sub.3.
[1206]
4 TABLE 4 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is SCH.sub.3.
[1207]
5 TABLE 5 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is SOCH.sub.3.
[1208]
6 TABLE 6 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is SO.sub.2CH.sub.3.
[1209]
7 TABLE 7 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is Cl.
[1210]
8 TABLE 8 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is F.
[1211]
9 TABLE 9 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is CO.sub.2CH.sub.3.
[1212]
10 TABLE 10 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is CH.sub.2OCH.sub.3.
[1213]
11 TABLE 11 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is CONH.sub.2.
[1214]
12 TABLE 12 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is CN.
[1215]
13 TABLE 13 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is CH.sub.2NH.sub.2.
[1216]
14 TABLE 14 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is CH.sub.2NHSO.sub.2CH.sub.3.
[1217]
15 TABLE 15 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is 1-imidazolyl-CH.sub.2.
[1218]
16 TABLE 16 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is 1-tetrazolyl-CH.sub.2--.
[1219]
17 TABLE 17 Examples 1-361 use the structures from Table 1 and the
corresponding A and B groups from Examples 1-361 of Table 1, and:
R.sup.1a is H.
Utility
[1220] The compounds of this invention are useful as anticoagulants
for the treatment or prevention of thromboembolic disorders in
mammals. The term "thromboembolic disorders" as used herein
includes arterial or venous cardiovascular or cerebrovascular
thromboembolic disorders, including, for example, unstable angina,
first or recurrent myocardial infarction, ischemic sudden death,
transient ischemic attack, stroke, atherosclerosis, venous
thrombosis, deep vein thrombosis, thrombophlebitis, arterial
embolism, coronary and cerebral arterial thrombosis, cerebral
embolism, kidney embolisms, and pulmonary embolisms. The
anticoagulant effect of compounds of the present invention is
believed to be due to inhibition of factor Xa or thrombin.
[1221] The effectiveness of compounds of the present invention as
inhibitors of factor Xa was determined using purified human factor
Xa and synthetic substrate. The rate of factor Xa hydrolysis of
chromogenic substrate S2222 (Kabi Pharmacia, Franklin, OH) was
measured both in the absence and presence of compounds of the
present invention. Hydrolysis of the substrate resulted in the
release of pNA, which was monitored spectrophotometrically by
measuring the increase in absorbance at 405 nM. A decrease in the
rate of absorbance change at 405 nm in the presence of inhibitor is
indicative of enzyme inhibition. The results of this assay are
expressed as inhibitory constant, K.sub.i.
[1222] Factor Xa determinations were made in 0.10 M sodium
phosphate buffer, pH 7.5, containing 0.20 M NaCl, and 0.5% PEG
8000. The Michaelis constant, K.sub.m, for substrate hydrolysis was
determined at 25.degree. C. using the method of Lineweaver and
Burk. Values of K.sub.i were determined by allowing 0.2-0.5 nM
human factor Xa (Enzyme Research Laboratories, South Bend, Ind.) to
react with the substrate (0.20 mM-1 mM) in the presence of
inhibitor. Reactions were allowed to go for 30 minutes and the
velocities (rate of absorbance change vs time) were measured in the
time frame of 25-30 minutes. The following relationship was used to
calculate K.sub.i values:
(v.sub.o-v.sub.s)/v.sub.s=I/(K.sub.i(1+S/K.sub.m))
[1223] where:
[1224] v.sub.o is the velocity of the control in the absence of
inhibitor;
[1225] v.sub.s is the velocity in the presence of inhibitor;
[1226] I is the concentration of inhibitor;
[1227] K.sub.i is the dissociation constant of the enzyme:inhibitor
complex;
[1228] S is the concentration of substrate;
[1229] K.sub.m is the Michaelis constant.
[1230] Compounds tested in the above assay are considered to be
active if they exhibit a K.sub.i of .ltoreq.10 .mu.M. Preferred
compounds of the present invention have K.sub.i's of .ltoreq.1
.mu.M. More preferred compounds of the present invention have
K.sub.i's of .ltoreq.0.1 .mu.M. Even more preferred compounds of
the present invention have K.sub.i's of .ltoreq.0.01 .mu.M. Still
more preferred compounds of the present invention have K.sub.i's of
.ltoreq.0.001 .mu.M.
[1231] The antithrombotic effect of compounds of the present
invention can be demonstrated in a rabbit arterio-venous (AV) shunt
thrombosis model. In this model, rabbits weighing 2-3 kg
anesthetized with a mixture of xylazine (10 mg/kg i.m.) and
ketamine (50 mg/kg i.m.) are used. A saline-filled AV shunt device
is connected between the femoral arterial and the femoral venous
cannulae. The AV shunt device consists of a piece of 6-cm tygon
tubing that contains a piece of silk thread. Blood will flow from
the femoral artery via the AV-shunt into the femoral vein. The
exposure of flowing blood to a silk thread will induce the
formation of a significant thrombus. After forty minutes, the shunt
is disconnected and the silk thread covered with thrombus is
weighed. Test agents or vehicle will be given (i.v., i.p., s.c., or
orally) prior to the opening of the AV shunt. The percentage
inhibition of thrombus formation is determined for each treatment
group. The ID50 values (dose which produces 50% inhibition of
thrombus formation) are estimated by linear regression.
[1232] The compounds of formula (I) may also be useful as
inhibitors of serine proteases, notably human thrombin, plasma
kallikrein and plasmin. Because of their inhibitory action, these
compounds are indicated for use in the prevention or treatment of
physiological reactions, blood coagulation and inflammation,
catalyzed by the aforesaid class of enzymes. Specifically, the
compounds have utility as drugs for the treatment of diseases
arising from elevated thrombin activity such as myocardial
infarction, and as reagents used as anticoagulants in the
processing of blood to plasma for diagnostic and other commercial
purposes.
[1233] Some compounds of the present invention were shown to be
direct acting inhibitors of the serine protease thrombin by their
ability to inhibit the cleavage of small molecule substrates by
thrombin in a purified system. In vitro inhibition constants were
determined by the method described by Kettner et al. in J. Biol.
Chem. 1990, 265, 18289-18297, herein incorporated by reference. In
these assays, thrombin-mediated hydrolysis of the chromogenic
substrate S2238 (Helena Laboratories, Beaumont, Tex.) was monitored
spectrophotometrically. Addition of an inhibitor to the assay
mixture results in decreased absorbance and is indicative of
thrombin inhibition. Human thrombin (Enzyme Research Laboratories,
Inc., South Bend, IN) at a concentration of 0.2 nM in 0.10 M sodium
phosphate buffer, pH 7.5, 0.20 M NaCl, and 0.5% PEG 6000, was
incubated with various substrate concentrations ranging from 0.20
to 0.02 mM. After 25 to 30 minutes of incubation, thrombin activity
was assayed by monitoring the rate of increase in absorbance at 405
nm that arises owing to substrate hydrolysis. Inhibition constants
were derived from reciprocal plots of the reaction velocity as a
function of substrate concentration using the standard method of
Lineweaver and Burk. Using the methodology described above, some
compounds of this invention were evaluated and found to exhibit a
K.sub.i of less than 10 .mu.m, thereby confirming the utility of
the compounds of the present invention as effective thrombin
inhibitors.
[1234] The compounds of the present invention can be administered
alone or in combination with one or more additional therapeutic
agents. These include other anticoagulant or coagulation inhibitory
agents, anti-platelet or platelet inhibitory agents, thrombin
inhibitors, or thrombolytic or fibrinolytic agents.
[1235] The compounds are administered to a mammal in a
therapeutically effective amount. By "therapeutically effective
amount" it is meant an amount of a compound of Formula I that, when
administered alone or in combination with an additional therapeutic
agent to a mammal, is effective to prevent or ameliorate the
thromboembolic disease condition or the progression of the
disease.
[1236] By "administered in combination" or "combination therapy" it
is meant that the compound of Formula I and one or more additional
therapeutic agents are administered concurrently to the mammal
being treated. When administered in combination each component may
be administered at the same time or sequentially in any order at
different points in time. Thus, each component may be administered
separately but sufficiently closely in time so as to provide the
desired therapeutic effect. Other anticoagulant agents (or
coagulation inhibitory agents) that may be used in combination with
the compounds of this invention include warfarin and heparin, as
well as other factor Xa inhibitors such as those described in the
publications identified above under Background of the
Invention.
[1237] The term anti-platelet agents (or platelet inhibitory
agents), as used herein, denotes agents that inhibit platelet
function such as by inhibiting the aggregation, adhesion or
granular secretion of platelets. Such agents include, but are not
limited to, the various known non-steroidal anti-inflammatory drugs
(NSAIDS) such as aspirin, ibuprofen, naproxen, sulindac,
indomethacin, mefenamate, droxicam, diclofenac, sulfinpyrazone, and
piroxicam, including pharmaceutically acceptable salts or prodrugs
thereof. Of the NSAIDS, aspirin (acetylsalicyclic acid or ASA), and
piroxicam are preferred. Other suitable anti-platelet agents
include ticlopidine, including pharmaceutically acceptable salts or
prodrugs thereof. Ticlopidine is also a preferred compound since it
is known to be gentle on the gastro-intestinal tract in use. Still
other suitable platelet inhibitory agents include IIb/IIIa
antagonists, thromboxane-A2-receptor antagonists and
thromboxane-A2-synthetase inhibitors, as well as pharmaceutically
acceptable salts or prodrugs thereof.
[1238] The term thrombin inhibitors (or anti-thrombin agents), as
used herein, denotes inhibitors of the serine protease thrombin. By
inhibiting thrombin, various thrombin-mediated processes, such as
thrombin-mediated platelet activation (that is, for example, the
aggregation of platelets, and/or the granular secretion of
plasminogen activator inhibitor-1 and/or serotonin) and/or fibrin
formation are disrupted. A number of thrombin inhibitors are known
to one of skill in the art and these inhibitors are contemplated to
be used in combination with the present compounds. Such inhibitors
include, but are not limited to, boroarginine derivatives,
boropeptides, heparins, hirudin and argatroban, including
pharmaceutically acceptable salts and prodrugs thereof.
Boroarginine derivatives and boropeptides include N-acetyl and
peptide derivatives of boronic acid, such as C-terminal
a-aminoboronic acid derivatives of lysine, ornithine, arginine,
homoarginine and corresponding isothiouronium analogs thereof. The
term hirudin, as used herein, includes suitable derivatives or
analogs of hirudin, referred to herein as hirulogs, such as
disulfatohirudin. Boropeptide thrombin inhibitors include compounds
described in Kettner et al., U.S. Pat. No. 5,187,157 and European
Patent Application Publication Number 293 881 A2, the disclosures
of which are hereby incorporated herein by reference. Other
suitable boroarginine derivatives and boropeptide thrombin
inhibitors include those disclosed in PCT Application Publication
Number 92/07869 and European Patent Application Publication Number
471,651 A2, the disclosures of which are hereby incorporated herein
by reference.
[1239] The term thrombolytics (or fibrinolytic) agents (or
thrombolytics or fibrinolytics), as used herein, denotes agents
that lyse blood clots (thrombi). Such agents include tissue
plasminogen activator, anistreplase, urokinase or streptokinase,
including pharmaceutically acceptable salts or prodrugs thereof.
The term anistreplase, as used herein, refers to anisoylated
plasminogen streptokinase activator complex, as described, for
example, in European Patent Application No. 028,489, the disclosure
of which is hereby incorporated herein by reference herein. The
term urokinase, as used herein, is intended to denote both dual and
single chain urokinase, the latter also being referred to herein as
prourokinase.
[1240] Administration of the compounds of Formula I of the
invention in combination with such additional therapeutic agent,
may afford an efficacy advantage over the compounds and agents
alone, and may do so while permitting the use of lower doses of
each. A lower dosage minimizes the potential of side effects,
thereby providing an increased margin of safety.
[1241] The compounds of the present invention are also useful as
standard or reference compounds, for example as a quality standard
or control, in tests or assays involving the inhibition of factor
Xa. Such compounds may be provided in a commercial kit, for
example, for use in pharmaceutical research involving factor Xa.
For example, a compound of the present invention could be used as a
reference in an assay to compare its known activity to a compound
with an unknown activity. This would ensure the experimenter that
the assay was being performed properly and provide a basis for
comparison, especially if the test compound was a derivative of the
reference compound. When developing new assays or protocols,
compounds according to the present invention could be used to test
their effectiveness. The compounds of the present invention may
also be used in diagnostic assays involving factor Xa. For example,
the presence of factor Xa in an unknown sample could be determined
by addition of chromogenic substrate S2222 to a series of solutions
containing test sample and optionally one of the compounds of the
present invention. If production of pNA is observed in the
solutions containing test sample, but not in the presence of a
compound of the present invention, then one would conclude factor
Xa was present.
Dosage and Formulation
[1242] The compounds of this invention can be administered in such
oral dosage forms as tablets, capsules (each of which includes
sustained release or timed release formulations), pills, powders,
granules, elixirs, tinctures, suspensions, syrups, and emulsions.
They may also be administered in intravenous (bolus or infusion),
intraperitoneal, subcutaneous, or intramuscular form, all using
dosage forms well known to those of ordinary skill in the
pharmaceutical arts. They can be administered alone, but generally
will be administered with a pharmaceutical carrier selected on the
basis of the chosen route of administration and standard
pharmaceutical practice.
[1243] The dosage regimen for the compounds of the present
invention will, of course, vary depending upon known factors, such
as the pharmacodynamic characteristics of the particular agent and
its mode and route of administration; the species, age, sex,
health, medical condition, and weight of the recipient; the nature
and extent of the symptoms; the kind of concurrent treatment; the
frequency of treatment; the route of administration, the renal and
hepatic function of the patient, and the effect desired. A
physician or veterinarian can determine and prescribe the effective
amount of the drug required to prevent, counter, or arrest the
progress of the thromboembolic disorder.
[1244] By way of general guidance, the daily oral dosage of each
active ingredient, when used for the indicated effects, will range
between about 0.001 to 1000 mg/kg of body weight, preferably
between about 0.01 to 100 mg/kg of body weight per day, and most
preferably between about 1.0 to 20 mg/kg/day. Intravenously, the
most preferred doses will range from about 1 to about 10
mg/kg/minute during a constant rate infusion. Compounds of this
invention may be administered in a single daily dose, or the total
daily dosage may be administered in divided doses of two, three, or
four times daily.
[1245] Compounds of this invention can be administered in
intranasal form via topical use of suitable intranasal vehicles, or
via transdermal routes, using transdermal skin patches. When
administered in the form of a transdermal delivery system, the
dosage administration will, of course, be continuous rather than
intermittent throughout the dosage regimen.
[1246] The compounds are typically administered in admixture with
suitable pharmaceutical diluents, excipients, or carriers
(collectively referred to herein as pharmaceutical carriers)
suitably selected with respect to the intended form of
administration, that is, oral tablets, capsules, elixirs, syrups
and the like, and consistent with conventional pharmaceutical
practices.
[1247] For instance, for oral administration in the form of a
tablet or capsule, the active drug component can be combined with
an oral, non-toxic, pharmaceutically acceptable, inert carrier such
as lactose, starch, sucrose, glucose, methyl callulose, magnesium
stearate, dicalcium phosphate, calcium sulfate, mannitol, sorbitol
and the like; for oral administration in liquid form, the oral drug
components can be combined with any oral, non-toxic,
pharmaceutically acceptable inert carrier such as ethanol,
glycerol, water, and the like. Moreover, when desired or necessary,
suitable binders, lubricants, disintegrating agents, and coloring
agents can also be incorporated into the mixture. Suitable binders
include starch, gelatin, natural sugars such as glucose or
beta-lactose, corn sweeteners, natural and synthetic gums such as
acacia, tragacanth, or sodium alginate, carboxymethylcellulose,
polyethylene glycol, waxes, and the like. Lubricants used in these
dosage forms include sodium oleate, sodium stearate, magnesium
stearate, sodium benzoate, sodium acetate, sodium chloride, and the
like. Disintegrators include, without limitation, starch, methyl
cellulose, agar, bentonite, xanthan gum, and the like.
[1248] The compounds of the present invention 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.
[1249] Compounds of the present invention may also be coupled with
soluble polymers as targetable drug carriers. Such polymers can
include polyvinylpyrrolidone, pyran copolymer,
polyhydroxypropylmethacrylamide-ph- enol,
polyhydroxyethylaspartamidephenol, or polyethyleneoxide-polylysine
substituted with palmitoyl residues. Furthermore, the compounds of
the present invention 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, polycyanoacylates, and crosslinked or
amphipathic block copolymers of hydrogels.
[1250] Dosage forms (pharmaceutical compositions) suitable for
administration may contain from about 1 milligram to about 100
milligrams of active ingredient per dosage unit. In these
pharmaceutical compositions the active ingredient will ordinarily
be present in an amount of about 0.5-95% by weight based on the
total weight of the composition.
[1251] Gelatin capsules may contain the active ingredient and
powdered carriers, such as lactose, starch, cellulose derivatives,
magnesium stearate, stearic acid, and the like. Similar diluents
can be used to make compressed tablets. Both tablets and capsules
can be manufactured as sustained release products to provide for
continuous release of medication over a period of hours. Compressed
tablets can be sugar coated or film coated to mask any unpleasant
taste and protect the tablet from the atmosphere, or enteric coated
for selective disintegration in the gastrointestinal tract.
[1252] Liquid dosage forms for oral administration can contain
coloring and flavoring to increase patient acceptance.
[1253] In general, water, a suitable oil, saline, aqueous dextrose
(glucose), and related sugar solutions and glycols such as
propylene glycol or polyethylene glycols are suitable carriers for
parenteral solutions. Solutions for parenteral administration
preferably contain a water soluble salt of the active ingredient,
suitable stabilizing agents, and if necessary, buffer substances.
Antioxidizing agents such as sodium bisulfite, sodium sulfite, or
ascorbic acid, either alone or combined, are suitable stabilizing
agents. Also used are citric acid and its salts and sodium EDTA. In
addition, parenteral solutions can contain preservatives, such as
benzalkonium chloride, methyl- or propyl-paraben, and
chlorobutanol.
[1254] Suitable pharmaceutical carriers are described in
Remington's Pharmaceutical Sciences, Mack Publishing Company, a
standard reference text in this field.
[1255] Representative useful pharmaceutical dosage-forms for
administration of the compounds of this invention can be
illustrated as follows:
[1256] Capsules
[1257] A large number of unit capsules can be prepared by filling
standard two-piece hard gelatin capsules each with 100 milligrams
of powdered active ingredient, 150 milligrams of lactose, 50
milligrams of cellulose, and 6 milligrams magnesium stearate.
[1258] Soft Gelatin Capsules
[1259] A mixture of active ingredient in a digestable oil such as
soybean oil, cottonseed oil or olive oil may be prepared and
injected by means of a positive displacement pump into gelatin to
form soft gelatin capsules containing 100 milligrams of the active
ingredient. The capsules should be washed and dried.
[1260] Tablets
[1261] Tablets may be prepared by conventional procedures so that
the dosage unit is 100 milligrams of active ingredient, 0.2
milligrams of colloidal silicon dioxide, 5 milligrams of magnesium
stearate, 275 milligrams of microcrystalline cellulose, 11
milligrams of starch and 98.8 milligrams of lactose. Appropriate
coatings may be applied to increase palatability or delay
absorption.
[1262] Injectable
[1263] A parenteral composition suitable for administration by
injection may be prepared by stirring 1.5% by weight of active
ingredient in 10% by volume propylene glycol and water. The
solution should be made isotonic with sodium chloride and
sterilized.
[1264] Suspension
[1265] An aqueous suspension can be prepared for oral
administration so that each 5 mL contain 100 mg of finely divided
active ingredient, 200 mg of sodium carboxymethyl cellulose, 5 mg
of sodium benzoate, 1.0 g of sorbitol solution, U.S.P., and 0.025
mL of vanillin.
[1266] Where the compounds of this invention are combined with
other anticoagulant agents, for example, a daily dosage may be
about 0.1 to 100 milligrams of the compound of Formula I and about
1 to 7.5 milligrams of the second anticoagulant, per kilogram of
patient body weight. For a tablet dosage form, the compounds of
this invention generally may be present in an amount of about 5 to
10 milligrams per dosage unit, and the second anti-coagulant in an
amount of about 1 to 5 milligrams per dosage unit.
[1267] Where the compounds of Formula I are administered in
combination with an anti-platelet agent, by way of general
guidance, typically a daily dosage may be about 0.01 to 25
milligrams of the compound of Formula I and about 50 to 150
milligrams of the anti-platelet agent, preferably about 0.1 to 1
milligrams of the compound of Formula I and about 1 to 3 milligrams
of antiplatelet agents, per kilogram of patient body weight.
[1268] Where the compounds of Formula I are adminstered in
combination with thrombolytic agent, typically a daily dosage may
be about 0.1 to 1 milligrams of the compound of Formula I, per
kilogram of patient body weight and, in the case of the
thrombolytic agents, the usual dosage of the thrombolyic agent when
administered alone may be reduced by about 70-80% when administered
with a compound of Formula I.
[1269] Where two or more of the foregoing second therapeutic agents
are administered with the compound of Formula I, generally the
amount of each component in a typical daily dosage and typical
dosage form may be reduced relative to the usual dosage of the
agent when administered alone, in view of the additive or
synergistic effect of the therapeutic agents when administered in
combination.
[1270] Particularly when provided as a single dosage unit, the
potential exists for a chemical interaction between the combined
active ingredients. For this reason, when the compound of Formula I
and a second therapeutic agent are combined in a single dosage unit
they are formulated such that although the active ingredients are
combined in a single dosage unit, the physical contact between the
active ingredients is minimized (that is, reduced). For example,
one active ingredient may be enteric coated. By enteric coating one
of the active ingredients, it is possible not only to minimize the
contact between the combined active ingredients, but also, it is
possible to control the release of one of these components in the
gastrointestinal tract such that one of these components is not
released in the stomach but rather is released in the intestines.
One of the active ingredients may also be coated with a material
that effects a sustained-release throughout the gastrointestinal
tract and also serves to minimize physical contact between the
combined active ingredients. Furthermore, the sustained-released
component can be additionally enteric coated such that the release
of this component occurs only in the intestine. Still another
approach would involve the formulation of a combination product in
which the one component is coated with a sustained and/or enteric
release polymer, and the other component is also coated with a
polymer such as a lowviscosity grade of hydroxypropyl
methylcellulose (HPMC) or other appropriate materials as known in
the art, in order to further separate the active components. The
polymer coating serves to form an additional barrier to interaction
with the other component. These as well as other ways of minimizing
contact between the components of combination products of the
present invention, whether administered in a single dosage form or
administered in separate forms but at the same time by the same
manner, will be readily apparent to those skilled in the art, once
armed with the present disclosure.
[1271] Numerous modifications and variations of the present
invention are possible in light of the above teachings. It is
therefore to be understood that within the scope of the appended
claims, the invention may be practiced otherwise that as
specifically described herein.
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