U.S. patent application number 15/207999 was filed with the patent office on 2016-11-03 for animal pest control method.
This patent application is currently assigned to E. I. DU PONT DE NEMOURS AND COMPANY. The applicant listed for this patent is GEORGE PHILIP LAHM, JEFFREY KEITH LONG, MING XU. Invention is credited to GEORGE PHILIP LAHM, JEFFREY KEITH LONG, MING XU.
Application Number | 20160317520 15/207999 |
Document ID | / |
Family ID | 40003056 |
Filed Date | 2016-11-03 |
United States Patent
Application |
20160317520 |
Kind Code |
A1 |
LAHM; GEORGE PHILIP ; et
al. |
November 3, 2016 |
ANIMAL PEST CONTROL METHOD
Abstract
Disclosed is a method for protecting an animal from a parasitic
invertebrate pest comprising treating an animal orally or by
injection with a pesticidally effective amount of a compound of
Formula 1, ##STR00001## wherein R.sup.1 is halogen, C.sub.1-C.sub.3
haloalkyl or C.sub.1-C.sub.3 haloalkoxy; R.sup.2 is H, halogen,
C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 haloalkyl or cyano; R.sup.3
is H, halogen, C.sub.1-C.sub.3 haloalkyl or C.sub.1-C.sub.3
haloalkoxy; R.sup.4 is halogen, C.sub.1-C.sub.3 alkyl,
C.sub.1-C.sub.3 haloalkyl or C.sub.1-C.sub.3 haloalkoxy; R.sup.5 is
H, CH.sub.3, C.sub.2-C.sub.4 alkylcarbonyl, C.sub.2-C.sub.4
haloalkylcarbonyl, C.sub.2-C.sub.5 alkoxycarbonyl or
CH.sub.2O(C.sub.1-C.sub.3 alkyl); R.sup.6 is C.sub.1-C.sub.6 alkyl,
C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl or
C.sub.3-C.sub.6 halocycloalkyl, each group substituted with one
R.sup.7; or R.sup.6 is (CH.sub.2).sub.mQ; and Q, R.sup.7, R.sup.8a
and R.sup.8b are as defined in the disclosure.
Inventors: |
LAHM; GEORGE PHILIP;
(WILMINGTON, DE) ; LONG; JEFFREY KEITH;
(WILMINGTON, DE) ; XU; MING; (NEWARK, DE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
LAHM; GEORGE PHILIP
LONG; JEFFREY KEITH
XU; MING |
WILMINGTON
WILMINGTON
NEWARK |
DE
DE
DE |
US
US
US |
|
|
Assignee: |
E. I. DU PONT DE NEMOURS AND
COMPANY
Wilmington
DE
|
Family ID: |
40003056 |
Appl. No.: |
15/207999 |
Filed: |
July 12, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12663848 |
Dec 10, 2009 |
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PCT/US08/68268 |
Jun 26, 2008 |
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15207999 |
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60937389 |
Jun 27, 2007 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A01N 43/80 20130101;
A61K 31/42 20130101; A61P 33/14 20180101; A61K 9/0019 20130101;
A61K 9/0053 20130101; A61P 33/00 20180101; A61P 33/10 20180101;
A61K 31/4439 20130101 |
International
Class: |
A61K 31/4439 20060101
A61K031/4439; A61K 31/42 20060101 A61K031/42; A01N 43/80 20060101
A01N043/80; A61K 9/00 20060101 A61K009/00 |
Claims
1. A method for protecting an animal from a parasitic invertebrate
pest comprising orally or parenterally administering to the animal
a pesticidally effective amount of a compound of Formula 1, an
N-oxide or a salt thereof ##STR00014## wherein R.sup.1 is halogen,
C.sub.1-C.sub.3 haloalkyl or C.sub.1-C.sub.3 haloalkoxy; R.sup.2 is
H, halogen, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 haloalkyl or
cyano; R.sup.3 is H, halogen, C.sub.1-C.sub.3 haloalkyl or
C.sub.1-C.sub.3 haloalkoxy; R.sup.4 is halogen, C.sub.1-C.sub.3
alkyl, C.sub.1-C.sub.3 haloalkyl or C.sub.1-C.sub.3 haloalkoxy;
R.sup.5 is H, CH.sub.3, C.sub.2-C.sub.4 alkylcarbonyl,
C.sub.2-C.sub.4 haloalkylcarbonyl, C.sub.2-C.sub.5 alkoxycarbonyl
or CH.sub.2O(C.sub.1-C.sub.3 alkyl); R.sup.6 is C.sub.1-C.sub.6
alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl or
C.sub.3-C.sub.6 halocycloalkyl, each group substituted with one
R.sup.7; or R.sup.6 is (CH.sub.2).sub.mQ; Q is a 4- to 6-membered
saturated ring containing carbon atoms and one O or S(O).sub.n as
ring members and optionally substituted with 1 or 2 R.sup.8a and
one R.sup.8b; R.sup.7 is OR.sup.9, S(O).sub.nR.sup.10 or
C(O)NR.sup.11R.sup.12; or R.sup.7 is pyridine or thiazole, each
optionally substituted with 1 or 2 R.sup.15; each R.sup.8a is
independently halogen, cyano or C.sub.1-C.sub.2 alkyl; R.sup.8b is
OR.sup.9, S(O).sub.nR.sup.10 or C(O)NR.sup.11R.sup.12; R.sup.9 is
H, CHO, C.sub.2-C.sub.4 alkylcarbonyl, C.sub.2-C.sub.4
haloalkylcarbonyl or C.sub.2-C.sub.5 alkoxycarbonyl; or R.sup.9 is
C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl, each optionally
substituted with one R.sup.13; or R.sup.9 is pyridine or thiazole,
each optionally substituted with 1 or 2 R.sup.15; R.sup.10 is
C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl, each optionally
substituted with one R.sup.13; or R.sup.10 is pyridine or thiazole,
each optionally substituted with 1 or 2 R.sup.15; R.sup.11 is H,
CHO, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 haloalkyl,
CH.sub.2O(C.sub.1-C.sub.3 alkyl), C.sub.2-C.sub.4 alkylcarbonyl,
C.sub.2-C.sub.4 haloalkylcarbonyl or C.sub.2-C.sub.5
alkoxycarbonyl; R.sup.12 is C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4
haloalkyl or C.sub.3-C.sub.6 cycloalkyl, each optionally
substituted with one R.sup.13; or R.sup.12 is H, C.sub.3-C.sub.6
alkenyl, C.sub.3-C.sub.6 haloalkenyl, C.sub.3-C.sub.6 alkynyl or
OR.sup.14; R.sup.13 is cyano, C.sub.3-C.sub.6 cycloalkyl,
C.sub.3-C.sub.6 halocycloalkyl, OH, OR.sup.14 or
S(O).sub.nR.sup.16; or R.sup.13 is pyridine or thiazole, each
optionally substituted with 1 or 2 R.sup.15; R.sup.14 is
C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl; each R.sup.15
is independently halogen, cyano, C.sub.1-C.sub.3 alkyl,
C.sub.1-C.sub.3 haloalkyl or C.sub.1-C.sub.3 haloalkoxy; R.sup.16
is C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl; m is 0 or 1;
and n is 0, 1 or 2.
2. The method of claim 1 wherein R.sup.4 is Cl or CH.sub.3; R.sup.5
is H; R.sup.6 is C.sub.1-C.sub.6 alkyl substituted with one
R.sup.7; and R.sup.7 is OR.sup.9, S(O).sub.nR.sup.10 or
C(O)NR.sup.11R.sup.12.
3. The method of claim 2 wherein R.sup.1 is Cl, Br, CF.sub.3,
OCF.sub.3 or OCH.sub.2CF.sub.3; R.sup.2 is H; and R.sup.3 is H, F,
Cl, Br or CF.sub.3.
4. The method of claim 3 wherein R.sup.4 is CH.sub.3; and R.sup.7
is C(O)NR.sup.11R.sup.12.
5. The method of claim 4 wherein R.sup.1 is CF.sub.3; and R.sup.3
is Cl, Br or CF.sub.3.
6. The method of claim 4 wherein R.sup.11 is H; and R.sup.12 is
C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl.
7. The method of claim 4 wherein R.sup.11 is H; and R.sup.12 is
cyclopropyl or cyclopropylmethyl.
8. The method of claim 1 wherein the pesticidally effective amount
of a compound of Formula 1 is administered orally.
9. The method of claim 1 wherein the pesticidally effective amount
of a compound of Formula 1 is administered parenterally.
10. The method of claim 9 wherein the pesticidally effective amount
of a compound of Formula 1 is administered by injection.
11. The method of claim 1 wherein the animal to be protected is a
mammal.
12. The method of claim 11 wherein the mammal to be protected is
livestock.
13. The method of claim 11 wherein the mammal to be protected is a
canine.
14. The method of claim 11 wherein the mammal to be protected is a
feline.
15. The method of claim 1 wherein the parasitic invertebrate pest
is an ectoparasite.
16. The method of claim 1 wherein the parasitic invertebrate pest
is an arthropod.
17. The method of claim 1 wherein the parasitic invertebrate pest
is a fly, mosquito, mite, tick, louse, flea, true bug or
maggot.
18. The method of claim 17 wherein the animal to be protected is a
cat or dog and the parasitic invertebrate pest is a flea, tick or
mite.
Description
FIELD OF THE INVENTION
[0001] This invention relates to a method for protecting an animal
from a parasitic pest and parasitic pest infestation.
BACKGROUND OF THE INVENTION
[0002] The control of animal parasites in animal health is
essential, especially in the areas of food production and companion
animals. Existing methods of treatment and parasite control are
being compromised due to growing resistance to many current
commercial parasiticides. The discovery of more effective ways to
control animal parasites is therefore imperative. In addition, it
is advantageous to discover ways to apply pesticides to animals
orally or parenterally so as to prevent the possible contamination
of humans or the surrounding environment.
[0003] PCT Patent Publication WO 05/085216 discloses isoxazoline
derivatives of Formula i as insecticides
##STR00002##
wherein, inter alia, each of A.sup.1, A.sup.2 and A.sup.3 are
independently C or N; G is a benzene ring; W is O or S; and X is
halogen or C.sub.1-C.sub.6 haloalkyl.
[0004] The method of the present invention is not disclosed in this
publication.
SUMMARY OF THE INVENTION
[0005] This invention pertains to a method for protecting animals
from a parasitic invertebrate pest comprising orally or
parenterally administering to the animal a pesticidally effective
amount of a compound of Formula 1 (including all geometric and
steroisomers), an N-oxide or a salt thereof
##STR00003##
wherein [0006] R.sup.1 is halogen, C.sub.1-C.sub.3 haloalkyl or
C.sub.1-C.sub.3 haloalkoxy; [0007] R.sup.2 is H, halogen,
C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 haloalkyl or cyano; [0008]
R.sup.3 is H, halogen, C.sub.1-C.sub.3 haloalkyl or C.sub.1-C.sub.3
haloalkoxy; [0009] R.sup.4 is halogen, C.sub.1-C.sub.3 alkyl,
C.sub.1-C.sub.3 haloalkyl or C.sub.1-C.sub.3 haloalkoxy; [0010]
R.sup.5 is H, CH.sub.3, C.sub.2-C.sub.4 alkylcarbonyl,
C.sub.2-C.sub.4 haloalkylcarbonyl, C.sub.2-C.sub.5 alkoxycarbonyl
or CH.sub.2O(C.sub.1-C.sub.3 alkyl); [0011] R.sup.6 is
C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6
cycloalkyl or C.sub.3-C.sub.6 halocycloalkyl, each group
substituted with one R.sup.7; or R.sup.6 is (CH.sub.2).sub.mQ;
[0012] Q is a 4- to 6-membered saturated ring containing carbon
atoms and one O or S(O).sub.n as ring members and optionally
substituted with 1 or 2 R.sup.8a and one R.sup.8b; [0013] R.sup.7
is OR.sup.9, S(O).sub.nR.sup.10 or C(O)NR.sup.11R.sup.12; or
R.sup.7 is pyridine or thiazole, each optionally substituted with 1
or 2 R.sup.15; [0014] each R.sup.8a is independently halogen, cyano
or C.sub.1-C.sub.2 alkyl; [0015] R.sup.8b is OR.sup.9,
S(O).sub.nR.sup.10 or C(O)NR.sup.11R.sup.12; [0016] R.sup.9 is H,
CHO, C.sub.2-C.sub.4 alkylcarbonyl, C.sub.2-C.sub.4
haloalkylcarbonyl or C.sub.2-C.sub.5 alkoxycarbonyl; or R.sup.9 is
C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl, each optionally
substituted with one R.sup.13; or R.sup.9 is pyridine or thiazole,
each optionally substituted with 1 or 2 R.sup.15; [0017] R.sup.10
is C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl, each
optionally substituted with one R.sup.13; or R.sup.10 is pyridine
or thiazole, each optionally substituted with 1 or 2 R.sup.15;
[0018] R.sup.11 is H, CHO, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4
haloalkyl, CH.sub.2O(C.sub.1-C.sub.3 alkyl), C.sub.2-C.sub.4
alkylcarbonyl, C.sub.2-C.sub.4 haloalkylcarbonyl or C.sub.2-C.sub.5
alkoxycarbonyl; [0019] R.sup.12 is C.sub.1-C.sub.4 alkyl,
C.sub.1-C.sub.4 haloalkyl or C.sub.3-C.sub.6 cycloalkyl, each
optionally substituted with one R.sup.13; or R.sup.12 is H,
C.sub.3-C.sub.6 alkenyl, C.sub.3-C.sub.6 haloalkenyl,
C.sub.3-C.sub.6 alkynyl or OR.sup.14; [0020] R.sup.13 is cyano,
C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 halocycloalkyl, OH,
OR.sup.14 or S(O).sub.nR.sup.16; or R.sup.13 is pyridine or
thiazole, each optionally substituted with 1 or 2 R.sup.15; [0021]
R.sup.14 is C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl;
[0022] each R.sup.15 is independently halogen, cyano,
C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 haloalkyl or C.sub.1-C.sub.3
haloalkoxy; [0023] R.sup.16 is C.sub.1-C.sub.4 alkyl or
C.sub.1-C.sub.4 haloalkyl; [0024] m is 0 or 1; and [0025] n is 0, 1
or 2.
[0026] This invention also relates to such method wherein the
parasitic invertebrate pest or its environment is contacted with a
composition comprising a biologically effective amount of a
compound of Formula 1, an N-oxide or a salt thereof, and at least
one additional component selected from the group consisting of
surfactants, solid diluents and liquid diluents, said composition
optionally further comprising a biologically effective amount of at
least one additional biologically active compound or agent.
[0027] This invention further provides a method for treating,
preventing, inhibiting and/or killing ecto- and/or endoparasites
comprising administering to and/or on the animal a pesticidally
effective amount of a compound of Formula 1, an N-oxide or a salt
thereof, (e.g., as a composition described herein). This invention
also relates to such method wherein a pesticidally effective amount
of a compound of Formula 1, an N-oxide or a salt thereof, (e.g., as
a composition described herein) is administered to the environment
(e.g., a stall or blanket) in which an animal resides.
DETAILS OF THE INVENTION
[0028] As used herein, the terms "comprises," "comprising,"
"includes," "including," "has," "having," "contains" or
"containing," or any other variation thereof, are intended to cover
a non-exclusive inclusion. For example, a composition, a mixture,
process, method, article, or apparatus that comprises a list of
elements is not necessarily limited to only those elements but may
include other elements not expressly listed or inherent to such
composition, mixture, process, method, article, or apparatus.
Further, unless expressly stated to the contrary, "or" refers to an
inclusive or and not to an exclusive or. For example, a condition A
or B is satisfied by any one of the following: A is true (or
present) and B is false (or not present), A is false (or not
present) and B is true (or present), and both A and B are true (or
present).
[0029] Also, the indefinite articles "a" and "an" preceding an
element or component of the invention are intended to be
nonrestrictive regarding the number of instances (i.e. occurrences)
of the element or component. Therefore "a" or "an" should be read
to include one or at least one, and the singular word form of the
element or component also includes the plural unless the number is
obviously meant to be singular.
[0030] As referred to in this disclosure, the terms "pest",
"invertebrate pest" and "parasitic invertebrate pest" include
arthropods, gastropods and nematodes of economic importance as
pests. The term "arthropod" includes insects, mites, spiders,
scorpions, centipedes, millipedes, pill bugs and symphylans. The
term "gastropod" includes snails, slugs and other Stylommatophora.
The term "nematode" includes all of the helminths, such as
roundworms, heartworms, and phytophagous nematodes (Nematoda),
flukes (Tematoda), Acanthocephala, and tapeworms (Cestoda).
[0031] In the context of this disclosure "invertebrate pest
control" means inhibition of invertebrate pest development
(including mortality, feeding reduction, and/or mating disruption),
and related expressions are defined analogously. The terms
"pesticidal" and "pesticidally" refer to observable effects on a
pest to provide protection of an animal from the pest. Pesticidal
effects typically relate to diminishing the occurrence or activity
of the target parasitic invertebrate pest. Such effects on the pest
include necrosis, death, retarded growth, diminished mobility or
lessened ability to remain on or in the host animal, reduced
feeding and inhibition of reproduction. These effects on parasitic
invertebrate pests provide control (including prevention, reduction
or elimination) of parasitic infestation or infection of the
animal.
[0032] A parasite "infestation" refers to the presence of parasites
in numbers that pose a risk to humans or animals. The infestation
can be in the environment (e.g., in human or animal housing,
bedding, and surrounding property or structures), on agricultural
crops or other types of plants, or on the skin or fur of an animal.
When the infestation is within an animal (e.g., in the blood or
other internal tissues), the term infestation is also intended to
be synonymous with the term "infection" as that term is generally
understood in the art, unless otherwise stated.
[0033] In the above recitations, the term "alkyl", used either
alone or in compound words such as "haloalkyl" includes
straight-chain or branched alkyls, such as methyl, ethyl, n-propyl,
i-propyl, or the different butyl, pentyl or hexyl isomers.
"Alkenyl" includes straight-chain or branched alkenes such as
ethenyl, 1-propenyl, 2-propenyl, and the different butenyl,
pentenyl and hexenyl isomers. "Alkenyl" also includes polyenes such
as 1,2-propadienyl and 2,4-hexadienyl. "Alkynyl" includes
straight-chain or branched alkynes such as ethynyl, 1-propynyl,
2-propynyl and the different butynyl, pentynyl and hexynyl isomers.
"Alkynyl" can also include moieties comprised of multiple triple
bonds such as 2,5-hexadiynyl.
[0034] "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl,
cyclopentyl and cyclohexyl. The term "cyclopropylmethyl" denotes
cyclopropyl substitution on a methyl moiety.
[0035] The term "halogen", either alone or in compound words such
as "haloalkyl", or when used in descriptions such as "alkyl
substituted with halogen" includes fluorine, chlorine, bromine or
iodine. Further, when used in compound words such as "haloalkyl",
or when used in descriptions such as "alkyl substituted with
halogen" said alkyl may be partially or fully substituted with
halogen atoms which may be the same or different. Examples of
"haloalkyl" or "alkyl substituted with halogen" include CF.sub.3,
CH.sub.2Cl, CH.sub.2CF.sub.3 and CCl.sub.2CF.sub.3. The terms
"halocycloalkyl", "haloalkoxy", "haloalkenyl", and the like, are
defined analogously to the term "haloalkyl". Examples of
"haloalkoxy" include OCF.sub.3, OCH.sub.2CCl.sub.3,
OCH.sub.2CH.sub.2CHF.sub.2 and OCH.sub.2CF.sub.3. Examples of
"haloalkenyl" include CH.sub.2CH.dbd.C(Cl).sub.2 and
CH.sub.2CH.dbd.CHCH.sub.2CF.sub.3.
[0036] "Alkylcarbonyl" denotes a straight-chain or branched alkyl
moiety bonded to a C(O) moiety. The chemical abbreviation C(O) as
used herein represents a carbonyl moiety. Examples of
"alkylcarbonyl" include C(O)CH.sub.3, C(O)CH.sub.2CH.sub.2CH.sub.3
and C(O)CH(CH.sub.3).sub.2.
[0037] The total number of carbon atoms in a substituent group is
indicated by the "C.sub.i-C.sub.j" prefix where i and j are numbers
from 1 to 6. For example, C.sub.1-C.sub.3 alkyl designates methyl
through propyl.
[0038] When a group contains a substituent which can be hydrogen,
for example R.sup.5 or R.sup.11, then when this substituent is
taken as hydrogen, it is recognized that this is equivalent to said
group being unsubstituted.
[0039] The term "ring member", as used in the definition of the
substituent Q in the Summary of the Invention, refers to an atom or
other moiety (e.g., O or S(O).sub.n) forming the backbone of a
ring. Examples of Q include
##STR00004##
[0040] Compounds of Formula 1 can exist as one or more
stereoisomers. The various stereoisomers include enantiomers,
diastereomers and atropisomers. One skilled in the art will
appreciate that one stereoisomer may be more active and/or may
exhibit beneficial effects when enriched relative to the other
stereoisomer(s) or when separated from the other stereoisomer(s).
Additionally, the skilled artisan knows how to separate, enrich,
and/or to selectively prepare said stereoisomers. The compounds
Formula 1 may be present as a mixture of stereoisomers, individual
stereoisomers or as an optically active form. For example, two
possible enantiomers of Formula 1 are depicted as Formula 1a and
Formula 1b involving the isoxazoline chiral center identified with
an asterisk (*). Analogously, other chiral centers are possible at,
for example, R.sup.1, R.sup.6, R.sup.9 and R.sup.11.
##STR00005##
[0041] Molecular depictions drawn herein follow standard
conventions for depicting stereochemistry. To indicate
stereoconfiguration, bonds rising from the plane of the drawing and
towards the viewer are denoted by solid wedges wherein the broad
end of the wedge is attached to the atom rising from the plane of
the drawing towards the viewer. Bonds going below the plane of the
drawing and away from the viewer are denoted by dashed wedges
wherein the narrow end of the wedge is attached to the atom further
away from the viewer. Constant width lines indicate bonds with a
direction opposite or neutral relative to bonds shown with solid or
dashed wedges; constant width lines also depict bonds in molecules
or parts of molecules in which no particular stereoconfiguration is
intended to be specified.
[0042] The more biologically active enantiomer is believed to be
Formula 1a. Formula 1a has the (S) configuration at the chiral
carbon, and Formula 1b has the (R) configuration at the chiral
carbon.
[0043] The method of this invention comprises racemic mixtures, for
example, equal amounts of the enantiomers of Formulae 1a and 1b. In
addition, the method of this invention includes compounds that are
enriched compared to the racemic mixture in an enantiomer of
Formula 1. Also included are the essentially pure enantiomers of
compounds of Formula 1, for example, Formula 1a and Formula 1b.
[0044] When enantiomerically enriched, one enantiomer is present in
greater amounts than the other, and the extent of enrichment can be
defined by an expression of enantiomeric excess ("ee"), which is
defined as (2x-1)100%, where x is the mole fraction of the dominant
enantiomer in the mixture (e.g., an ee of 20% corresponds to a
60:40 ratio of enantiomers).
[0045] Preferably the compositions of Formula 1 have at least a 50%
enantiomeric excess; more preferably at least a 75% enantiomeric
excess; still more preferably at least a 90% enantiomeric excess;
and the most preferably at least a 94% enantiomeric excess of the
more active isomer. Of particular note are enantiomerically pure
embodiments of the more active isomer.
[0046] Compounds of Formula 1 can comprise additional chiral
centers. The method of this invention comprises racemic mixtures as
well as enriched and essentially pure stereoconfigurations at these
additional chiral centers. Compounds of Formula 1 can exist as one
or more conformational isomers due to restricted rotation about the
amide bond in Formula 1. The method of this invention comprises
mixtures of conformational isomers. In addition, the method of this
invention includes compounds that are enriched in one conformer
relative to others.
[0047] Embodiments of the present invention as described in the
Summary of the Invention include those described below. In the
following Embodiments, reference to "a compound of Formula 1"
includes the definitions of substituents specified in the Summary
of the Invention unless further defined in the Embodiments.
Embodiment 1
[0048] The method described in the Summary of the Invention wherein
the pesticidally effective compound is selected from an isoxazoline
of Formula 1 (including all geometric and steroisomers), an N-oxide
or a salt thereof
##STR00006##
wherein [0049] R.sup.1 is halogen, C.sub.1-C.sub.3 haloalkyl or
C.sub.1-C.sub.3 haloalkoxy; [0050] R.sup.2 is H, halogen,
C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 haloalkyl or cyano; [0051]
R.sup.3 is H, halogen, C.sub.1-C.sub.3 haloalkyl or C.sub.1-C.sub.3
haloalkoxy; [0052] R.sup.4 is halogen, C.sub.1-C.sub.3 alkyl,
C.sub.1-C.sub.3 haloalkyl or C.sub.1-C.sub.3 haloalkoxy; [0053]
R.sup.5 is H, CH.sub.3, C.sub.2-C.sub.4 alkylcarbonyl,
C.sub.2-C.sub.4 haloalkylcarbonyl, C.sub.2-C.sub.5 alkoxycarbonyl
or CH.sub.2O(C.sub.1-C.sub.3 alkyl); [0054] R.sup.6 is
C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6
cycloalkyl or C.sub.3-C.sub.6 halocycloalkyl, each group
substituted with one R.sup.7; or R.sup.6 is (CH.sub.2).sub.mQ;
[0055] Q is a 4- to 6-membered saturated ring containing carbon
atoms and one O or S(O).sub.n as ring members and optionally
substituted with 1 or 2 R.sup.8a and one R.sup.8b; [0056] R.sup.7
is OR.sup.9, S(O).sub.nR.sup.10 or C(O)NR.sup.11R.sup.12; or
R.sup.7 is pyridine or thiazole, each optionally substituted with 1
or 2 R.sup.15; [0057] each R.sup.8a is independently halogen, cyano
or C.sub.1-C.sub.2 alkyl; [0058] R.sup.8b is OR.sup.9,
S(O).sub.nR.sup.10 or C(O)NR.sup.11R.sup.12; [0059] R.sup.9 is H,
CHO, C.sub.2-C.sub.4 alkylcarbonyl, C.sub.2-C.sub.4
haloalkylcarbonyl or C.sub.2-C.sub.5 alkoxycarbonyl; or R.sup.9 is
C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl, each optionally
substituted with one R.sup.13; or R.sup.9 is pyridine or thiazole,
each optionally substituted with 1 or 2 R.sup.15; [0060] R.sup.10
is C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl, each
optionally substituted with one R.sup.13; or R.sup.10 is pyridine
or thiazole, each optionally substituted with 1 or 2 R.sup.15;
[0061] R.sup.11 is H, CHO, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4
haloalkyl, CH.sub.2O(C.sub.1-C.sub.3 alkyl), C.sub.2-C.sub.4
alkylcarbonyl, C.sub.2-C.sub.4 haloalkylcarbonyl or C.sub.2-C.sub.5
alkoxycarbonyl; R.sup.12 is C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4
haloalkyl or C.sub.3-C.sub.6 cycloalkyl, each optionally
substituted with one R.sup.13; or R.sup.12 is H, C.sub.3-C.sub.6
alkenyl, C.sub.3-C.sub.6 haloalkenyl, C.sub.3-C.sub.6 alkynyl or
OR.sup.14; [0062] R.sup.13 is cyano, C.sub.3-C.sub.6 cycloalkyl,
C.sub.3-C.sub.6 halocycloalkyl, OH, OR.sup.14 or
S(O).sub.nR.sup.16; or R.sup.13 is pyridine or thiazole, each
optionally substituted with 1 or 2 R.sup.15; [0063] R.sup.14 is
C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl; [0064] each
R.sup.15 is independently halogen, cyano, C.sub.1-C.sub.3 alkyl,
C.sub.1-C.sub.3 haloalkyl or C.sub.1-C.sub.3 haloalkoxy; [0065]
R.sup.16 is C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl;
[0066] m is 0 or 1; and [0067] n is 0, 1 or 2.
Embodiment 2
[0068] The method of Embodiment 1 wherein R.sup.1 is Cl, Br,
CF.sub.3, OCF.sub.3 or OCH.sub.2CF.sub.3.
Embodiment 3
[0069] The method of Embodiment 2 wherein R.sup.1 is Cl, Br or
CF.sub.3.
Embodiment 4
[0070] The method of Embodiment 3 wherein R.sup.1 is Cl.
Embodiment 5
[0071] The method of Embodiment 3 wherein R.sup.1 is Br.
Embodiment 6
[0072] The method of Embodiment 3 wherein R.sup.1 is CF.sub.3.
Embodiment 7
[0073] The method of Embodiment 1 wherein R.sup.2 is H, F or
Cl.
Embodiment 8
[0074] The method of Embodiment 7 wherein R.sup.2 is H.
Embodiment 9
[0075] The method of Embodiment 7 wherein R.sup.2 is F.
Embodiment 10
[0076] The method of Embodiment 7 wherein R.sup.2 is Cl.
Embodiment 11
[0077] The method of Embodiment 1 wherein R.sup.3 is H, F, Cl, Br
or CF.sub.3.
Embodiment 12
[0078] The method of Embodiment 11 wherein R.sup.3 is H, Cl, Br or
CF.sub.3.
Embodiment 13
[0079] The method of Embodiment 12 wherein R.sup.3 is Cl, Br or
CF.sub.3.
Embodiment 14
[0080] The method of Embodiment 11 wherein R.sup.3 is H.
Embodiment 15
[0081] The method of Embodiment 11 wherein R.sup.3 is Cl.
Embodiment 16
[0082] The method of Embodiment 11 wherein R.sup.3 is Br.
Embodiment 17
[0083] The method of Embodiment 11 wherein R.sup.3 is CF.sub.3.
Embodiment 18
[0084] The method of Embodiment 1 wherein R.sup.4 is halogen or
C.sub.1-C.sub.3 alkyl.
Embodiment 19
[0085] The method of Embodiment 18 wherein R.sup.4 is halogen or
methyl.
Embodiment 20
[0086] The method of Embodiment 19 wherein R.sup.4 is halogen.
Embodiment 21
[0087] The method of Embodiment 20 wherein R.sup.4 is Cl.
Embodiment 22
[0088] The method of Embodiment 19 wherein R.sup.4 is methyl.
Embodiment 23
[0089] The method of Embodiment 1 wherein R.sup.5 is H.
Embodiment 24
[0090] The method of Embodiment 1 wherein R.sup.6 is halogen or
C.sub.1-C.sub.6 alkyl.
Embodiment 25
[0091] The method of Embodiment 1 wherein R.sup.6 is
C.sub.1-C.sub.6 alkyl substituted with one R.sup.7;
Embodiment 26
[0092] The method of Embodiment 1 wherein R.sup.7 is OR.sup.9,
S(O).sub.nR.sup.10 or C(O)NR.sup.11R.sup.12.
Embodiment 27
[0093] The method of Embodiment 26 wherein R.sup.7 is OR.sup.9.
Embodiment 28
[0094] The method of Embodiment 26 wherein R.sup.7 is
S(O).sub.nR.sup.10.
Embodiment 29
[0095] The method of Embodiment 26 wherein R.sup.7 is
C(O)NR.sup.11R.sup.12.
Embodiment 30
[0096] The method of Embodiment 1 wherein R.sup.9 is H or
C.sub.1-C.sub.4 alkyl.
Embodiment 31
[0097] The method of Embodiment 30 wherein R.sup.9 is H or
methyl.
Embodiment 32
[0098] The method of Embodiment 31 wherein R.sup.9 is H.
Embodiment 33
[0099] The method of Embodiment 31 wherein R.sup.9 is methyl.
Embodiment 34
[0100] The method of Embodiment 1 wherein R.sup.10 is
C.sub.1-C.sub.4 alkyl.
Embodiment 35
[0101] The method of Embodiment 1 wherein R.sup.11 is H.
Embodiment 36
[0102] The method of Embodiment 1 wherein R.sup.12 is
C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl, each optionally
substituted with one R.sup.13.
Embodiment 37
[0103] The method of Embodiment 1 wherein R.sup.12 is
C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl.
Embodiment 38
[0104] The method of Embodiment 37 wherein R.sup.12 is
C.sub.1-C.sub.4 haloalkyl.
Embodiment 38a
[0105] The method of Embodiment 1 wherein R.sup.12 is cyclopropyl
or cyclopropylmethyl.
Embodiment 39
[0106] The method of Embodiment 1 wherein R.sup.13 is cyano, OH,
OR.sup.14 or S(O).sub.nR.sup.16.
Embodiment 40
[0107] The method of Embodiment 39 wherein R.sup.13 is cyano.
Embodiment 41
[0108] The method of Embodiment 39 wherein R.sup.13 is OH.
Embodiment 42
[0109] The method of Embodiment 39 wherein R.sup.13 is
OR.sup.14.
Embodiment 43
[0110] The method of Embodiment 39 wherein R.sup.13 is
S(O).sub.nR.sup.16.
Embodiment 44
[0111] The method of Embodiment 1 wherein the pesticidally
effective amount of a compound of Formula 1 is administered
orally.
Embodiment 45
[0112] The method of Embodiment 1 wherein the pesticidally
effective amount of a compound of Formula 1 is administered
parenterally.
Embodiment 46
[0113] The method of Embodiment 45 wherein the pesticidally
effective amount of a compound of Formula 1 is administered by
injection.
Embodiment 47
[0114] The method of Embodiment 1 wherein the animal to be
protected is a vertebrate.
Embodiment 48
[0115] The method of Embodiment 47 wherein the vertebrate to be
protected is a mammal, avian or fish.
Embodiment 49
[0116] The method of Embodiment 48 wherein the vertebrate to be
protected is a mammal.
Embodiment 50
[0117] The method of Embodiment 48 wherein the vertebrate to be
protected is an avian.
Embodiment 51
[0118] The method of Embodiment 48 wherein the vertebrate to be
protected is a fish.
Embodiment 52
[0119] The method of Embodiment 49 wherein the mammal to be
protected is a human.
Embodiment 53
[0120] The method of Embodiment 49 wherein the mammal to be
protected is livestock.
Embodiment 54
[0121] The method of Embodiment 49 wherein the mammal to be
protected is a canine.
Embodiment 55
[0122] The method of Embodiment 49 wherein the mammal to be
protected is a feline.
Embodiment 56
[0123] The method of Embodiment 1 wherein the parasitic
invertebrate pest is an ectoparasite.
Embodiment 57
[0124] The method of Embodiment 1 wherein the parasitic
invertebrate pest is an endoparasite.
Embodiment 58
[0125] The method of Embodiment 1 wherein the parasitic
invertebrate pest is an helminth.
Embodiment 59
[0126] The method of Embodiment 1 wherein the parasitic
invertebrate pest is an arthropod.
Embodiment 60
[0127] The method of Embodiment 1 wherein the parasitic
invertebrate pest is a fly, mosquito, mite, tick, louse, flea, true
bug or maggot.
Embodiment 61
[0128] The method of Embodiment 1 wherein the parasitic
invertebrate pest is a fly, mosquito, mite, tick, louse, flea, bed
bug, kissing bug or maggot.
Embodiment 62
[0129] The method of Embodiment 61 wherein the parasitic
invertebrate pest is a fly or maggot.
Embodiment 63
[0130] The method of Embodiment 61 wherein the parasitic
invertebrate pest is a mosquito.
Embodiment 64
[0131] The method of Embodiment 61 wherein the parasitic
invertebrate pest is a tick or mite.
Embodiment 65
[0132] The method of Embodiment 61 wherein the parasitic
invertebrate pest is a louse.
Embodiment 66
[0133] The method of Embodiment 61 wherein the parasitic
invertebrate pest is a flea.
Embodiment 67
[0134] The method of Embodiment 61 wherein the parasitic
invertebrate pest is a true bug.
Embodiment 68
[0135] The method of Embodiment 61 wherein the parasitic
invertebrate pest is a bed bug or kissing bug.
Embodiment 69
[0136] The method of Embodiment 61 wherein the animal to be
protected is a cat or dog and the parasitic invertebrate pest is a
flea, tick or mite.
Embodiment 70
[0137] The method of Embodiment 44 wherein the parasiticidally
effective amount of a compound of Formula 1 is administered orally
two times a year.
Embodiment 71
[0138] The method of Embodiment 44 wherein the parasiticidally
effective amount of a compound of Formula 1 is administered orally
once a month.
Embodiment 72
[0139] The method of Embodiment 44 wherein the parasiticidally
effective amount of a compound of Formula 1 is administered orally
two times a month.
[0140] Embodiments of this invention, including Embodiments 1-72
above as well as any other embodiments described herein, can be
combined in any manner.
[0141] Combinations of Embodiments 1-43 are illustrated by:
Embodiment A
[0142] The method of Embodiment 1 wherein [0143] R.sup.1 is Cl, Br
or CF.sub.3; [0144] R.sup.2 is H, F or Cl; and [0145] R.sup.3 is H,
Cl, Br or CF.sub.3.
Embodiment B
[0146] A method of Embodiment A wherein [0147] R.sup.1 and R.sup.3
are Cl; and [0148] R.sup.2 is H.
Embodiment C
[0149] A method of Embodiment A wherein [0150] R.sup.1 and R.sup.3
are Br; and [0151] R.sup.2 is H.
Embodiment D
[0152] A method of Embodiment A wherein [0153] R.sup.1 and R.sup.3
are CF.sub.3; and [0154] R.sup.2 is H.
Embodiment E
[0155] A method of Embodiment A wherein [0156] R.sup.1, R.sup.2 and
R.sup.3 are Cl.
Embodiment F
[0157] A method of Embodiment A wherein [0158] R.sup.1 and R.sup.3
are Cl; and [0159] R.sup.2 is F.
Embodiment G
[0160] A method of Embodiment A wherein [0161] R.sup.1 is CF.sub.3;
and [0162] R.sup.2 and R.sup.3 are H.
Embodiment H
[0163] A method of Embodiment A wherein [0164] R.sup.4 is methyl;
and [0165] R.sup.5 is H.
Embodiment I
[0166] A method of Embodiment A wherein [0167] R.sup.5 is H; [0168]
R.sup.6 is C.sub.1-C.sub.6 alkyl substituted with one R.sup.7; and
[0169] R.sup.7 is OR.sup.9, S(O).sub.nR.sup.10 or
C(O)NR.sup.11R.sup.12.
Embodiment J
[0170] A method of Embodiment A wherein [0171] R.sup.7 is
C(O)NR.sup.11R.sup.12; and [0172] R.sup.12 is C.sub.1-C.sub.4 alkyl
or C.sub.1-C.sub.4 haloalkyl, each optionally substituted with one
R.sup.13.
Embodiment K
[0173] A method of Embodiment A wherein [0174] R.sup.4 is Cl or
CH.sub.3; [0175] R.sup.5 is H; [0176] R.sup.6 is C.sub.1-C.sub.6
alkyl substituted with one R.sup.7; and [0177] R.sup.7 is OR.sup.9,
S(O).sub.11R.sup.10 or C(O)NR.sup.11R.sup.12.
Embodiment L
[0178] A method of Embodiment K wherein [0179] R.sup.1 is Cl, Br,
CF.sub.3, OCF.sub.3 or OCH.sub.2CF.sub.3; [0180] R.sup.2 is H; and
[0181] R.sup.3 is H, F, Cl, Br or CF.sub.3.
Embodiment M
[0182] A method of Embodiment L wherein [0183] R.sup.4 is CH.sub.3;
and [0184] R.sup.7 is C(O)NR.sup.11R.sup.12.
Embodiment N
[0185] A method of Embodiment M wherein [0186] R.sup.1 is CF.sub.3;
and [0187] R.sup.3 is Cl, Br or CF.sub.3.
Embodiment O
[0188] A method of Embodiment M wherein [0189] R.sup.11 is H; and
[0190] R.sup.12 is C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4
haloalkyl.
Embodiment P
[0191] A method of Embodiment M wherein [0192] R.sup.11 is H; and
[0193] R.sup.12 is cyclopropyl or cyclopropylmethyl.
[0194] Specific embodiments include the method of Embodiment 1
wherein compounds of Formula 1 are selected from the group
consisting of: [0195]
4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-
-methyl-N-(2-pyridinylmethyl)benzamide, [0196]
4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-
-methyl-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]benzamide,
[0197]
4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-
-methyl-N-[2-(methylthio)ethyl]benzamide, [0198]
4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-
-methyl-N-[2-(methylsulfinyl)ethyl]benzamide, [0199]
4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-
-methyl-N-[2-(methylsulfonyl)ethyl]benzamide, and [0200]
4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-
-methyl-N-[1-methyl-3-(methylthio)propyl]benzamide.
[0201] Further specific embodiments include the method of
Embodiment 1 wherein compounds of Formula 1 are selected from Table
A and B. The following abbreviation is used in Table A: c-Pr means
cyclopropyl.
TABLE-US-00001 TABLE A ##STR00007## R.sup.1 R.sup.3 R.sup.12
R.sup.a is H Cl Cl CH.sub.3 Cl Cl CH.sub.2CH.sub.3 Cl Cl
CH(CH.sub.3).sub.2 Cl Cl CH.sub.2CF.sub.3 Cl Cl c-Pr Cl Cl
CH.sub.2--c-Pr Cl CF.sub.3 CH.sub.3 Cl CF.sub.3 CH.sub.2CH.sub.3 Cl
CF.sub.3 CH(CH.sub.3).sub.2 Cl CF.sub.3 CH.sub.2CF.sub.3 Cl
CF.sub.3 c-Pr Cl CF.sub.3 CH.sub.2--c-Pr Cl OCH.sub.2CF.sub.3
CH.sub.3 Cl OCH.sub.2CF.sub.3 CH.sub.2CH.sub.3 Cl OCH.sub.2CF.sub.3
CH(CH.sub.3).sub.2 Cl OCH.sub.2CF.sub.3 CH.sub.2CF.sub.3 Cl
OCH.sub.2CF.sub.3 c-Pr Cl OCH.sub.2CF.sub.3 CH.sub.2--c-Pr Br
CF.sub.3 CH.sub.3 Br CF.sub.3 CH.sub.2CH.sub.3 Br CF.sub.3
CH(CH.sub.3).sub.2 Br CF.sub.3 CH.sub.2CF.sub.3 Br CF.sub.3 c-Pr Br
CF.sub.3 CH.sub.2--c-Pr CF.sub.3 CF.sub.3 CH.sub.3 CF.sub.3
CF.sub.3 CH.sub.2CH.sub.3 CF.sub.3 CF.sub.3 CH(CH.sub.3).sub.2
CF.sub.3 CF.sub.3 CH.sub.2CF.sub.3 CF.sub.3 CF.sub.3 c-Pr CF.sub.3
CF.sub.3 CH.sub.2--c-Pr R.sup.a is CH.sub.3 Cl Cl CH.sub.3 Cl Cl
CH.sub.2CH.sub.3 Cl Cl CH(CH.sub.3).sub.2 Cl Cl CH.sub.2CF.sub.3 Cl
Cl c-Pr Cl Cl CH.sub.2--c-Pr Cl CF.sub.3 CH.sub.3 Cl CF.sub.3
CH.sub.2CH.sub.3 Cl CF.sub.3 CH(CH.sub.3).sub.2 Cl CF.sub.3
CH.sub.2CF.sub.3 Cl CF.sub.3 c-Pr Cl CF.sub.3 CH.sub.2--c-Pr Cl
OCH.sub.2CF.sub.3 CH.sub.3 Cl OCH.sub.2CF.sub.3 CH.sub.2CH.sub.3 Cl
OCH.sub.2CF.sub.3 CH(CH.sub.3).sub.2 Cl OCH.sub.2CF.sub.3
CH.sub.2CF.sub.3 Cl OCH.sub.2CF.sub.3 c-Pr Cl OCH.sub.2CF.sub.3
CH.sub.2--c-Pr Br CF.sub.3 CH.sub.3 Br CF.sub.3 CH.sub.2CH.sub.3 Br
CF.sub.3 CH(CH.sub.3).sub.2 Br CF.sub.3 CH.sub.2CF.sub.3 Br
CF.sub.3 c-Pr Br CF.sub.3 CH.sub.2--c-Pr CF.sub.3 CF.sub.3 CH.sub.3
CF.sub.3 CF.sub.3 CH.sub.2CH.sub.3 CF.sub.3 CF.sub.3
CH(CH.sub.3).sub.2 CF.sub.3 CF.sub.3 CH.sub.2CF.sub.3 CF.sub.3
CF.sub.3 c-Pr CF.sub.3 CF.sub.3 CH.sub.2--c-Pr
TABLE-US-00002 TABLE B ##STR00008## R.sup.1 R.sup.3 n R.sup.b
R.sup.a is H Cl Cl 0 CH.sub.3 Cl Cl 1 CH.sub.3 Cl Cl 2 CH.sub.3 Cl
Cl 0 CH.sub.2CH.sub.3 Cl Cl 1 CH.sub.2CH.sub.3 Cl Cl 2
CH.sub.2CH.sub.3 Cl CF.sub.3 0 CH.sub.3 Cl CF.sub.3 1 CH.sub.3 Cl
CF.sub.3 2 CH.sub.3 Cl CF.sub.3 0 CH.sub.2CH.sub.3 Cl CF.sub.3 1
CH.sub.2CH.sub.3 Cl CF.sub.3 2 CH.sub.2CH.sub.3 Cl
OCH.sub.2CF.sub.3 0 CH.sub.3 Cl OCH.sub.2CF.sub.3 1 CH.sub.3 Cl
OCH.sub.2CF.sub.3 2 CH.sub.3 Cl OCH.sub.2CF.sub.3 0
CH.sub.2CH.sub.3 Cl OCH.sub.2CF.sub.3 1 CH.sub.2CH.sub.3 Cl
OCH.sub.2CF.sub.3 2 CH.sub.2CH.sub.3 Br CF.sub.3 0 CH.sub.3 Br
CF.sub.3 1 CH.sub.3 Br CF.sub.3 2 CH.sub.3 Br CF.sub.3 0
CH.sub.2CH.sub.3 Br CF.sub.3 1 CH.sub.2CH.sub.3 Br CF.sub.3 2
CH.sub.2CH.sub.3 CF.sub.3 CF.sub.3 0 CH.sub.3 CF.sub.3 CF.sub.3 1
CH.sub.3 CF.sub.3 CF.sub.3 2 CH.sub.3 CF.sub.3 CF.sub.3 0
CH.sub.2CH.sub.3 CF.sub.3 CF.sub.3 1 CH.sub.2CH.sub.3 CF.sub.3
CF.sub.3 2 CH.sub.2CH.sub.3 R.sup.a is CH.sub.3 Cl Cl 0 CH.sub.3 Cl
Cl 1 CH.sub.3 Cl Cl 2 CH.sub.3 Cl Cl 0 CH.sub.2CH.sub.3 Cl Cl 1
CH.sub.2CH.sub.3 Cl Cl 2 CH.sub.2CH.sub.3 Cl CF.sub.3 0 CH.sub.3 Cl
CF.sub.3 1 CH.sub.3 Cl CF.sub.3 2 CH.sub.3 Cl CF.sub.3 0
CH.sub.2CH.sub.3 Cl CF.sub.3 1 CH.sub.2CH.sub.3 Cl CF.sub.3 2
CH.sub.2CH.sub.3 Cl OCH.sub.2CF.sub.3 0 CH.sub.3 Cl
OCH.sub.2CF.sub.3 1 CH.sub.3 Cl OCH.sub.2CF.sub.3 2 CH.sub.3 Cl
OCH.sub.2CF.sub.3 0 CH.sub.2CH.sub.3 Cl OCH.sub.2CF.sub.3 1
CH.sub.2CH.sub.3 Cl OCH.sub.2CF.sub.3 2 CH.sub.2CH.sub.3 Br
CF.sub.3 0 CH.sub.3 Br CF.sub.3 1 CH.sub.3 Br CF.sub.3 2 CH.sub.3
Br CF.sub.3 0 CH.sub.2CH.sub.3 Br CF.sub.3 1 CH.sub.2CH.sub.3 Br
CF.sub.3 2 CH.sub.2CH.sub.3 CF.sub.3 CF.sub.3 0 CH.sub.3 CF.sub.3
CF.sub.3 1 CH.sub.3 CF.sub.3 CF.sub.3 2 CH.sub.3 CF.sub.3 CF.sub.3
0 CH.sub.2CH.sub.3 CF.sub.3 CF.sub.3 1 CH.sub.2CH.sub.3 CF.sub.3
CF.sub.3 2 CH.sub.2CH.sub.3
[0202] The compounds of Formula 1 or any of Embodiments 1-43 or
Embodiments A-P can be used for the protection of an animal from an
invertebrate parasitic pest by oral or parenteral administration of
the compound.
[0203] Therefore, the invention is understood to include the
compounds of Formula 1 or any of Embodiments 1-43 or Embodiments
A-P (and compositions containing them) for use as an animal
medicament, or more particularly a parasiticidal animal medicament.
The animals to be protected are as defined in any of Embodiments
47-55. The invertebrate parasitic pests are as defined in any of
Embodiments 56-68. The medicament may be in oral or parenteral
dosage forms.
[0204] The invention is also understood to include the use of
compounds of Formula 1 or any of Embodiments 1-43 or Embodiments
A-P in the manufacture of medicaments for the protection of an
animal from a an invertebrate parasitic pest. The animals to be
protected are as defined in any of Embodiments 47-55. The
invertebrate parasitic pests are as defined in any of Embodiments
56-68. The medicament may be in oral or parenteral dosage
forms.
[0205] The invention is also understood to include compounds of
Formula 1 or any of Embodiments 1-43 or Embodiments A-P for use in
the manufacture of medicaments for the protection of an animal from
an invertebrate parasitic pest. The animals to be protected are as
defined in any of Embodiments 47-55. The invertebrate parasitic
pests are as defined in any of Embodiments 56-68. The medicament
may be in oral or parenteral dosage forms.
[0206] The invention is also understood to include compounds of
Formula 1 or any of Embodiments 1-43 or Embodiments A-P packaged
and presented for the protection of an animal from an invertebrate
parasitic pest. The animals to be protected are as defined in any
of Embodiments 47-55. The invertebrate parasitic pests are as
defined in any of Embodiments 56-68. The compounds of the invention
may be packaged and presented as oral or parenteral dosage
forms.
[0207] The invention is also understood to include a process for
manufacturing a composition for protecting an animal from an
invertebrate parasitic pest characterized in that a compound of
Claim 1 is admixed with at least one pharmaceutically or
veterinarily acceptable carrier. The animals to be protected are as
defined in any of Embodiments 47-55. The invertebrate parasitic
pests are as defined in any of Embodiments 56-68. The compositions
of the invention may be packaged and presented as oral or
parenteral dosage forms.
[0208] Isoxazolines of Formula 1 can be prepared as described in
PCT Patent Publication WO 2005/085216.
[0209] One skilled in the art will appreciate that not all pyridine
heterocycles can form N-oxides; one skilled in the art will
recognize those pyridine heterocycles which can form N-oxides.
Synthetic methods for the preparation of N-oxides of pyridine
heterocycles are very well known by one skilled in the art
including the oxidation of heterocycles with peroxy acids such as
peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide,
alkyl hydroperoxides such as t-butyl hydroperoxide, sodium
perborate, and dioxiranes such as dimethyldioxirane. These methods
for the preparation of N-oxides have been extensively described and
reviewed in the literature, see for example: T. L. Gilchrist in
Comprehensive Organic Synthesis, vol. 7, pp 748-750, S. V. Ley,
Ed., Pergamon Press; M. Tisler and B. Stanovnik in Comprehensive
Heterocyclic Chemistry, vol. 3, pp 18-20, A. J. Boulton and A.
McKillop, Eds., Pergamon Press; M. R. Grimmett and B. R. T. Keene
in Advances in Heterocyclic Chemistry, vol. 43, pp 149-161, A. R.
Katritzky, Ed., Academic Press; M. Tisler and B. Stanovnik in
Advances in Heterocyclic Chemistry, vol. 9, pp 285-291, A. R.
Katritzky and A. J. Boulton, Eds., Academic Press; and G. W. H.
Cheeseman and E. S. G. Werstiuk in Advances in Heterocyclic
Chemistry, vol. 22, pp 390-392, A. R. Katritzky and A. J. Boulton,
Eds., Academic Press.
[0210] One skilled in the art recognizes that because in the
environment and under physiological conditions salts of chemical
compounds are in equilibrium with their corresponding nonsalt
forms, salts share the biological utility of the nonsalt forms.
Thus a wide variety of salts of the compounds of Formula 1 are
useful for control of invertebrate pests and animal parasites. The
salts of the compounds of Formula 1 include acid-addition salts
with inorganic or organic acids such as hydrobromic, hydrochloric,
nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic,
maleic, malonic, oxalic, propionic, salicylic, tartaric,
4-toluenesulfonic or valeric acids. Accordingly, the method of the
present invention comprises compounds selected from Formula 1,
N-oxides and salts thereof.
[0211] By the procedures described in PCT Patent Publication WO
2005/085216 together with methods known in the art, the following
compounds of Tables 1-4 can be prepared. These tables disclose
specific compounds illustrative of compounds of Formula 1 useful in
the present method. The following abbreviations are used in the
Tables which follow: Me means methyl, Et means ethyl, n-Pr means
CH.sub.2CH.sub.2CH.sub.3, i-Pr means CH(CH.sub.3).sub.2, c-Pr means
cyclopropyl, i-Bu means CH.sub.2CH(CH.sub.3).sub.2, s-Bu means
CH(CH.sub.3)CH.sub.2CH.sub.3, t-Bu means C(CH.sub.3).sub.3, S(O)
means sulfinyl, S(O).sub.2 means sulfonyl, and C(O) means
carbonyl.
TABLE-US-00003 TABLE 1 ##STR00009## R.sup.6 R.sup.1 is Cl, R.sup.3
is Cl CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is Br, R.sup.3 is Br
CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is CF.sub.3, R.sup.3 is
H CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is CF.sub.3, R.sup.3 is
F CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is CF.sub.3, R.sup.3 is
Cl CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is CF.sub.3, R.sup.3 is
Br CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is CF.sub.3, R.sup.3 is
CF.sub.3 CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is OCF.sub.3, R.sup.3 is
Cl CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is OCH.sub.2CF.sub.3,
R.sup.3 is F CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is OCH.sub.2CF.sub.3,
R.sup.3 is Cl CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is OCH.sub.2CF.sub.3,
R.sup.3 is Br CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3
TABLE-US-00004 TABLE 2 ##STR00010## R.sup.6 R.sup.1 is Cl, R.sup.2
is Cl, R.sup.3 is Cl CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is Cl, R.sup.2 is F,
R.sup.3 is Cl CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is Cl, R.sup.2 is CN,
R.sup.3 is Cl CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is Br, R.sup.2 is H,
R.sup.3 is H CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is Br, R.sup.2 is H,
R.sup.3 is Cl CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is Br, R.sup.2 is F,
R.sup.3 is Br CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is Br, R.sup.2 is Cl,
R.sup.3 is Cl CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is Br, R.sup.2 is Cl,
R.sup.3 is Br CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is OCF.sub.3, R.sup.2 is
H, R.sup.3 is Br CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3
TABLE-US-00005 TABLE 3 ##STR00011## R.sup.6 R.sup.1 is Cl, R.sup.3
is Cl CH.sub.2CH.sub.2OH CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2O(i-Pr) CH.sub.2CH(Me)OH CH.sub.2CH(CF.sub.3)OH
CH.sub.2C(Me).sub.2OH CH.sub.2C(CF.sub.3)(Me)OH CH(Me)CH.sub.2OH
C(Me).sub.2CH.sub.2OH CH(Et)CH.sub.2OH CH(i-Pr)CH.sub.2OH
CH(i-Bu)CH.sub.2OH CH(Me)CH(CF.sub.3)OH CH.sub.2CH.sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2CH(CF.sub.3)OH CH(Me)CH.sub.2CH.sub.2OH
CH.sub.2CH(Me)CH.sub.2OH CH.sub.2C(Me).sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH(Me)OH CH.sub.2CH.sub.2C(Me).sub.2OH
CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2S(i-Pr) CH.sub.2CH.sub.2S(i-Bu) CH.sub.2CH(Me)SMe
CH.sub.2CH(CF.sub.3)SMe CH.sub.2C(Me).sub.2SMe CH(Me)CH.sub.2SMe
C(Me).sub.2CH.sub.2SMe CH(Et)CH.sub.2SMe CH(i-Pr)CH.sub.2SMe
CH(i-Bu)CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2CH(Me)SMe
CH.sub.2CH.sub.2CH(CF.sub.3)SMe CH(Me)CH.sub.2CH.sub.2SMe
CH(Et)CH.sub.2CH.sub.2SMe CH.sub.2CH(Me)CH.sub.2SMe
CH.sub.2C(Me).sub.2CH.sub.2SMe CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2S(O)(i-Pr) CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH(Me)S(O)Me CH.sub.2CH(CF.sub.3)S(O)Me
CH.sub.2C(Me).sub.2S(O)Me CH(Me)CH.sub.2S(O)Me CH(Et)CH.sub.2S(O)Me
CH(i-Bu)CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH.sub.2CH(Me)S(O)Me CH.sub.2CH.sub.2CH(CF.sub.3)S(O)Me
CH(Me)CH.sub.2CH.sub.2S(O)Me CH(Et)CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH(Me)CH.sub.2S(O)Me CH.sub.2C(Me).sub.2CH.sub.2S(O)Me
CH.sub.2(2-pyridinyl) CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2SO.sub.2(i-Pr) CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH(CF.sub.3)SO.sub.2Me CH.sub.2C(Me).sub.2SO.sub.2Me
CH(Me)CH.sub.2SO.sub.2Me C(Me).sub.2CH.sub.2SO.sub.2Me
CH(Et)CH.sub.2SO.sub.2Me CH(i-Pr)CH.sub.2SO.sub.2Me
CH(i-Bu)CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH.sub.2CH(CF.sub.3)SO.sub.2Me
CH(Me)CH.sub.2CH.sub.2SO.sub.2Me CH(Et)CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH(Me)CH.sub.2SO.sub.2Me
CH.sub.2C(Me).sub.2CH.sub.2SO.sub.2Me
CH.sub.2C(O)NHCH.sub.2CH.sub.2F CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl
CH.sub.2C(O)NHCH.sub.2CHF.sub.2 CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me) CH.sub.2C(O)NHCH.sub.2C(Me).sub.2F
CH.sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CHFCF.sub.3
CH.sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH(CF.sub.3).sub.2 CH.sub.2C(O)NHC(Me).sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
CH.sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2F CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)F CH(Me)C(O)NHCH.sub.2C(Me).sub.2F
CH(Me)C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CHFCF.sub.3
CH(Me)C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH(CF.sub.3).sub.2 CH(Me)C(O)NHC(Me).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3
CH(Me)C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)NHCH.sub.2CHF.sub.2
C(Me).sub.2C(O)NHCH.sub.2CF.sub.3 C(Me).sub.2C(O)NHCH.sub.2CH(Me)F
C(Me).sub.2C(O)NHCH.sub.2C(Me).sub.2F
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CHFCF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NH(c-Pr)
CH.sub.2C(O)NH(CH.sub.2--c-Pr) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et) CH.sub.2C(O)NH(n-Pr)
CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(n-Bu) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH.sub.2C(O)NMe.sub.2 CH.sub.2C(O)NMe(Et)
CH.sub.2C(O)NEt.sub.2 CH.sub.2C(O)NMe(n-Pr) CH.sub.2C(O)NMe(i-Pr)
CH.sub.2C(O)NMe(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(n-Bu)
CH(Me)C(O)NH(i-Bu) CH(Me)C(O)NH(s-Bu) C(Me).sub.2C(O)NH(Me)
C(Me).sub.2C(O)NH(Et) C(Me).sub.2C(O)NH(n-Pr)
C(Me).sub.2C(O)NH(i-Pr) (Me).sub.2C(O)NH(n-Bu)
C(Me).sub.2C(O)NH(i-Bu) C(Me).sub.2C(O)NH(s-Bu)
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
CH.sub.2C(O)N(Me)CH.sub.2CHF.sub.2
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH(Me)CF.sub.3 CH.sub.2C(O)N(Me)CH(CF.sub.3).sub.2
CH.sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2F CH(Me)C(O)N(Me)CH.sub.2CH.sub.2Cl
CH(Me)C(O)N(Me)CH.sub.2CHF.sub.2 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH(Me)CF.sub.3 CH(Me)C(O)N(Me)CH(CF.sub.3).sub.2
CH(Me)C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)N(Me)CH.sub.2CHF.sub.2
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH(Me)CF.sub.3
C(Me).sub.2C(O)N(Me)CH(CF.sub.3).sub.2
C(Me).sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(Me)CF.sub.3 C(Me).sub.2C(O)NHCH(CF.sub.3).sub.2
C(Me).sub.2C(O)NHC(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(i-Pr)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) R.sup.1 is Br, R.sup.3 is Br
CH.sub.2CH.sub.2OH CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2O(i-Pr) CH.sub.2CH(Me)OH CH.sub.2CH(CF.sub.3)OH
CH.sub.2C(Me).sub.2OH CH.sub.2C(CF.sub.3)(Me)OH CH(Me)CH.sub.2OH
C(Me).sub.2CH.sub.2OH CH(Et)CH.sub.2OH CH(i-Pr)CH.sub.2OH
CH(i-Bu)CH.sub.2OH CH(Me)CH(CF.sub.3)OH CH.sub.2CH.sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2CH(CF.sub.3)OH CH(Me)CH.sub.2CH.sub.2OH
CH.sub.2CH(Me)CH.sub.2OH CH.sub.2C(Me).sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH(Me)OH CH.sub.2CH.sub.2C(Me).sub.2OH
CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2S(i-Pr) CH.sub.2CH.sub.2S(i-Bu) CH.sub.2CH(Me)SMe
CH.sub.2CH(CF.sub.3)SMe CH.sub.2C(Me).sub.2SMe CH(Me)CH.sub.2SMe
C(Me).sub.2CH.sub.2SMe CH(Et)CH.sub.2SMe CH(i-Pr)CH.sub.2SMe
CH(i-Bu)CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2CH(Me)SMe
CH.sub.2CH.sub.2CH(CF.sub.3)SMe CH(Me)CH.sub.2CH.sub.2SMe
CH(Et)CH.sub.2CH.sub.2SMe CH.sub.2CH(Me)CH.sub.2SMe
CH.sub.2C(Me).sub.2CH.sub.2SMe CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2S(O)(i-Pr)
CH.sub.2CH.sub.2S(O)(i-Bu) CH.sub.2CH(Me)S(O)Me
CH.sub.2CH(CF.sub.3)S(O)Me CH.sub.2C(Me).sub.2S(O)Me
CH(Me)CH.sub.2S(O)Me CH(Et)CH.sub.2S(O)Me CH(i-Bu)CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2CH.sub.2S(O)(i-Bu) CH.sub.2CH.sub.2CH(Me)S(O)Me
CH.sub.2CH.sub.2CH(CF.sub.3)S(O)Me CH(Me)CH.sub.2CH.sub.2S(O)Me
CH(Et)CH.sub.2CH.sub.2S(O)Me CH.sub.2CH(Me)CH.sub.2S(O)Me
CH.sub.2C(Me).sub.2CH.sub.2S(O)Me CH.sub.2(2-pyridinyl)
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2SO.sub.2(i-Pr)
CH.sub.2CH(Me)SO.sub.2Me CH.sub.2CH(CF.sub.3)SO.sub.2Me
CH.sub.2C(Me).sub.2SO.sub.2Me CH(Me)CH.sub.2SO.sub.2Me
C(Me).sub.2CH.sub.2SO.sub.2Me CH(Et)CH.sub.2SO.sub.2Me
CH(i-Pr)CH.sub.2SO.sub.2Me CH(i-Bu)CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH.sub.2CH(CF.sub.3)SO.sub.2Me
CH(Me)CH.sub.2CH.sub.2SO.sub.2Me CH(Et)CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH(Me)CH.sub.2SO.sub.2Me
CH.sub.2C(Me).sub.2CH.sub.2SO.sub.2Me
CH.sub.2C(O)NHCH.sub.2CH.sub.2F CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl
CH.sub.2C(O)NHCH.sub.2CHF.sub.2 CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me) CH.sub.2C(O)NHCH.sub.2C(Me).sub.2F
CH.sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CHFCF.sub.3
CH.sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH(CF.sub.3).sub.2 CH.sub.2C(O)NHC(Me).sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
CH.sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2F CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)F CH(Me)C(O)NHCH.sub.2C(Me).sub.2F
CH(Me)C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CHFCF.sub.3
CH(Me)C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH(CF.sub.3).sub.2 CH(Me)C(O)NHC(Me).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3
CH(Me)C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)NHCH.sub.2CHF.sub.2
C(Me).sub.2C(O)NHCH.sub.2CF.sub.3 C(Me).sub.2C(O)NHCH.sub.2CH(Me)F
C(Me).sub.2C(O)NHCH.sub.2C(Me).sub.2F
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CHFCF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NH(c-Pr)
CH.sub.2C(O)NH(CH.sub.2--c-Pr) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et) CH.sub.2C(O)NH(n-Pr)
CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(n-Bu) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH.sub.2C(O)NMe.sub.2 CH.sub.2C(O)NMe(Et)
CH.sub.2C(O)NEt.sub.2 CH.sub.2C(O)NMe(n-Pr) CH.sub.2C(O)NMe(i-Pr)
CH.sub.2C(O)NMe(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(n-Bu)
CH(Me)C(O)NH(i-Bu) CH(Me)C(O)NH(s-Bu) C(Me).sub.2C(O)NH(Me)
C(Me).sub.2C(O)NH(Et) C(Me).sub.2C(O)NH(n-Pr)
C(Me).sub.2C(O)NH(i-Pr) (Me).sub.2C(O)NH(n-Bu)
C(Me).sub.2C(O)NH(i-Bu) C(Me).sub.2C(O)NH(s-Bu)
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
CH.sub.2C(O)N(Me)CH.sub.2CHF.sub.2
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH(Me)CF.sub.3 CH.sub.2C(O)N(Me)CH(CF.sub.3).sub.2
CH.sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2F CH(Me)C(O)N(Me)CH.sub.2CH.sub.2Cl
CH(Me)C(O)N(Me)CH.sub.2CHF.sub.2 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH(Me)CF.sub.3 CH(Me)C(O)N(Me)CH(CF.sub.3).sub.2
CH(Me)C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)N(Me)CH.sub.2CHF.sub.2
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH(Me)CF.sub.3
C(Me).sub.2C(O)N(Me)CH(CF.sub.3).sub.2
C(Me).sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(Me)CF.sub.3 C(Me).sub.2C(O)NHCH(CF.sub.3).sub.2
C(Me).sub.2C(O)NHC(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(i-Pr)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) R.sup.1 is CF.sub.3, R.sup.3 is H
CH.sub.2CH.sub.2OH CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2O(i-Pr) CH.sub.2CH(Me)OH CH.sub.2CH(CF.sub.3)OH
CH.sub.2C(Me).sub.2OH CH.sub.2C(CF.sub.3)(Me)OH CH(Me)CH.sub.2OH
C(Me).sub.2CH.sub.2OH CH(Et)CH.sub.2OH CH(i-Pr)CH.sub.2OH
CH(i-Bu)CH.sub.2OH CH(Me)CH(CF.sub.3)OH CH.sub.2CH.sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2CH(CF.sub.3)OH CH(Me)CH.sub.2CH.sub.2OH
CH.sub.2CH(Me)CH.sub.2OH CH.sub.2C(Me).sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH(Me)OH CH.sub.2CH.sub.2C(Me).sub.2OH
CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2S(i-Pr) CH.sub.2CH.sub.2S(i-Bu) CH.sub.2CH(Me)SMe
CH.sub.2CH(CF.sub.3)SMe CH.sub.2C(Me).sub.2SMe CH(Me)CH.sub.2SMe
C(Me).sub.2CH.sub.2SMe CH(Et)CH.sub.2SMe CH(i-Pr)CH.sub.2SMe
CH(i-Bu)CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2CH(Me)SMe
CH.sub.2CH.sub.2CH(CF.sub.3)SMe CH(Me)CH.sub.2CH.sub.2SMe
CH(Et)CH.sub.2CH.sub.2SMe CH.sub.2CH(Me)CH.sub.2SMe
CH.sub.2C(Me).sub.2CH.sub.2SMe CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2S(O)(i-Pr) CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH(Me)S(O)Me CH.sub.2CH(CF.sub.3)S(O)Me
CH.sub.2C(Me).sub.2S(O)Me CH(Me)CH.sub.2S(O)Me CH(Et)CH.sub.2S(O)Me
CH(i-Bu)CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH.sub.2CH(Me)S(O)Me CH.sub.2CH.sub.2CH(CF.sub.3)S(O)Me
CH(Me)CH.sub.2CH.sub.2S(O)Me CH(Et)CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH(Me)CH.sub.2S(O)Me CH.sub.2C(Me).sub.2CH.sub.2S(O)Me
CH.sub.2(2-pyridinyl) CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2SO.sub.2(i-Pr) CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH(CF.sub.3)SO.sub.2Me CH.sub.2C(Me).sub.2SO.sub.2Me
CH(Me)CH.sub.2SO.sub.2Me C(Me).sub.2CH.sub.2SO.sub.2Me
CH(Et)CH.sub.2SO.sub.2Me CH(i-Pr)CH.sub.2SO.sub.2Me
CH(i-Bu)CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH.sub.2CH(CF.sub.3)SO.sub.2Me
CH(Me)CH.sub.2CH.sub.2SO.sub.2Me CH(Et)CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH(Me)CH.sub.2SO.sub.2Me
CH.sub.2C(Me).sub.2CH.sub.2SO.sub.2Me
CH.sub.2C(O)NHCH.sub.2CH.sub.2F CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl
CH.sub.2C(O)NHCH.sub.2CHF.sub.2 CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me) CH.sub.2C(O)NHCH.sub.2C(Me).sub.2F
CH.sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CHFCF.sub.3
CH.sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH(CF.sub.3).sub.2 CH.sub.2C(O)NHC(Me).sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
CH.sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2F CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)F CH(Me)C(O)NHCH.sub.2C(Me).sub.2F
CH(Me)C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CHFCF.sub.3
CH(Me)C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH(CF.sub.3).sub.2 CH(Me)C(O)NHC(Me).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3
CH(Me)C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)NHCH.sub.2CHF.sub.2
C(Me).sub.2C(O)NHCH.sub.2CF.sub.3 C(Me).sub.2C(O)NHCH.sub.2CH(Me)F
C(Me).sub.2C(O)NHCH.sub.2C(Me).sub.2F
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CHFCF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NH(c-Pr)
CH.sub.2C(O)NH(CH.sub.2--c-Pr) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et) CH.sub.2C(O)NH(n-Pr)
CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(n-Bu) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH.sub.2C(O)NMe.sub.2 CH.sub.2C(O)NMe(Et)
CH.sub.2C(O)NEt.sub.2 CH.sub.2C(O)NMe(n-Pr) CH.sub.2C(O)NMe(i-Pr)
CH.sub.2C(O)NMe(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(n-Bu)
CH(Me)C(O)NH(i-Bu) CH(Me)C(O)NH(s-Bu) C(Me).sub.2C(O)NH(Me)
C(Me).sub.2C(O)NH(Et) C(Me).sub.2C(O)NH(n-Pr)
C(Me).sub.2C(O)NH(i-Pr) (Me).sub.2C(O)NH(n-Bu)
C(Me).sub.2C(O)NH(i-Bu) C(Me).sub.2C(O)NH(s-Bu)
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
CH.sub.2C(O)N(Me)CH.sub.2CHF.sub.2
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH(Me)CF.sub.3 CH.sub.2C(O)N(Me)CH(CF.sub.3).sub.2
CH.sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2F CH(Me)C(O)N(Me)CH.sub.2CH.sub.2Cl
CH(Me)C(O)N(Me)CH.sub.2CHF.sub.2 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH(Me)CF.sub.3 CH(Me)C(O)N(Me)CH(CF.sub.3).sub.2
CH(Me)C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)N(Me)CH.sub.2CHF.sub.2
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH(Me)CF.sub.3
C(Me).sub.2C(O)N(Me)CH(CF.sub.3).sub.2
C(Me).sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(Me)CF.sub.3 C(Me).sub.2C(O)NHCH(CF.sub.3).sub.2
C(Me).sub.2C(O)NHC(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(i-Pr)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) R.sup.1 is CF.sub.3, R.sup.3 is F
CH.sub.2CH.sub.2OH CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2O(i-Pr) CH.sub.2CH(Me)OH CH.sub.2CH(CF.sub.3)OH
CH.sub.2C(Me).sub.2OH CH.sub.2C(CF.sub.3)(Me)OH CH(Me)CH.sub.2OH
C(Me).sub.2CH.sub.2OH CH(Et)CH.sub.2OH CH(i-Pr)CH.sub.2OH
CH(i-Bu)CH.sub.2OH CH(Me)CH(CF.sub.3)OH CH.sub.2CH.sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2CH(CF.sub.3)OH CH(Me)CH.sub.2CH.sub.2OH
CH.sub.2CH(Me)CH.sub.2OH CH.sub.2C(Me).sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH(Me)OH CH.sub.2CH.sub.2C(Me).sub.2OH
CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2S(i-Pr) CH.sub.2CH.sub.2S(i-Bu) CH.sub.2CH(Me)SMe
CH.sub.2CH(CF.sub.3)SMe CH.sub.2C(Me).sub.2SMe CH(Me)CH.sub.2SMe
C(Me).sub.2CH.sub.2SMe CH(Et)CH.sub.2SMe CH(i-Pr)CH.sub.2SMe
CH(i-Bu)CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2CH(Me)SMe
CH.sub.2CH.sub.2CH(CF.sub.3)SMe CH(Me)CH.sub.2CH.sub.2SMe
CH(Et)CH.sub.2CH.sub.2SMe CH.sub.2CH(Me)CH.sub.2SMe
CH.sub.2C(Me).sub.2CH.sub.2SMe CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2S(O)(i-Pr) CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH(Me)S(O)Me CH.sub.2CH(CF.sub.3)S(O)Me
CH.sub.2C(Me).sub.2S(O)Me CH(Me)CH.sub.2S(O)Me CH(Et)CH.sub.2S(O)Me
CH(i-Bu)CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH.sub.2CH(Me)S(O)Me CH.sub.2CH.sub.2CH(CF.sub.3)S(O)Me
CH(Me)CH.sub.2CH.sub.2S(O)Me CH(Et)CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH(Me)CH.sub.2S(O)Me CH.sub.2C(Me).sub.2CH.sub.2S(O)Me
CH.sub.2(2-pyridinyl) CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2SO.sub.2(i-Pr) CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH(CF.sub.3)SO.sub.2Me CH.sub.2C(Me).sub.2SO.sub.2Me
CH(Me)CH.sub.2SO.sub.2Me C(Me).sub.2CH.sub.2SO.sub.2Me
CH(Et)CH.sub.2SO.sub.2Me CH(i-Pr)CH.sub.2SO.sub.2Me
CH(i-Bu)CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH.sub.2CH(CF.sub.3)SO.sub.2Me
CH(Me)CH.sub.2CH.sub.2SO.sub.2Me CH(Et)CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH(Me)CH.sub.2SO.sub.2Me
CH.sub.2C(Me).sub.2CH.sub.2SO.sub.2Me
CH.sub.2C(O)NHCH.sub.2CH.sub.2F CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl
CH.sub.2C(O)NHCH.sub.2CHF.sub.2 CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me) CH.sub.2C(O)NHCH.sub.2C(Me).sub.2F
CH.sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CHFCF.sub.3
CH.sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH(CF.sub.3).sub.2 CH.sub.2C(O)NHC(Me).sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
CH.sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2F CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)F CH(Me)C(O)NHCH.sub.2C(Me).sub.2F
CH(Me)C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CHFCF.sub.3
CH(Me)C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH(CF.sub.3).sub.2 CH(Me)C(O)NHC(Me).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3
CH(Me)C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)NHCH.sub.2CHF.sub.2
C(Me).sub.2C(O)NHCH.sub.2CF.sub.3 C(Me).sub.2C(O)NHCH.sub.2CH(Me)F
C(Me).sub.2C(O)NHCH.sub.2C(Me).sub.2F
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CHFCF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NH(c-Pr)
CH.sub.2C(O)NH(CH.sub.2--c-Pr) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et) CH.sub.2C(O)NH(n-Pr)
CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(n-Bu) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH.sub.2C(O)NMe.sub.2 CH.sub.2C(O)NMe(Et)
CH.sub.2C(O)NEt.sub.2 CH.sub.2C(O)NMe(n-Pr) CH.sub.2C(O)NMe(i-Pr)
CH.sub.2C(O)NMe(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(n-Bu)
CH(Me)C(O)NH(i-Bu) CH(Me)C(O)NH(s-Bu) C(Me).sub.2C(O)NH(Me)
C(Me).sub.2C(O)NH(Et) C(Me).sub.2C(O)NH(n-Pr)
C(Me).sub.2C(O)NH(i-Pr)
(Me).sub.2C(O)NH(n-Bu) C(Me).sub.2C(O)NH(i-Bu)
C(Me).sub.2C(O)NH(s-Bu) CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
CH.sub.2C(O)N(Me)CH.sub.2CHF.sub.2
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH(Me)CF.sub.3 CH.sub.2C(O)N(Me)CH(CF.sub.3).sub.2
CH.sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2F CH(Me)C(O)N(Me)CH.sub.2CH.sub.2Cl
CH(Me)C(O)N(Me)CH.sub.2CHF.sub.2 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH(Me)CF.sub.3 CH(Me)C(O)N(Me)CH(CF.sub.3).sub.2
CH(Me)C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)N(Me)CH.sub.2CHF.sub.2
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH(Me)CF.sub.3
C(Me).sub.2C(O)N(Me)CH(CF.sub.3).sub.2
C(Me).sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(Me)CF.sub.3 C(Me).sub.2C(O)NHCH(CF.sub.3).sub.2
C(Me).sub.2C(O)NHC(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(i-Pr)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) R.sup.1 is CF.sub.3, R.sup.3 is Cl
CH.sub.2CH.sub.2OH CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2O(i-Pr) CH.sub.2CH(Me)OH CH.sub.2CH(CF.sub.3)OH
CH.sub.2C(Me).sub.2OH CH.sub.2C(CF.sub.3)(Me)OH CH(Me)CH.sub.2OH
C(Me).sub.2CH.sub.2OH CH(Et)CH.sub.2OH CH(i-Pr)CH.sub.2OH
CH(i-Bu)CH.sub.2OH CH(Me)CH(CF.sub.3)OH CH.sub.2CH.sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2CH(CF.sub.3)OH CH(Me)CH.sub.2CH.sub.2OH
CH.sub.2CH(Me)CH.sub.2OH CH.sub.2C(Me).sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH(Me)OH CH.sub.2CH.sub.2C(Me).sub.2OH
CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2S(i-Pr) CH.sub.2CH.sub.2S(i-Bu) CH.sub.2CH(Me)SMe
CH.sub.2CH(CF.sub.3)SMe CH.sub.2C(Me).sub.2SMe CH(Me)CH.sub.2SMe
C(Me).sub.2CH.sub.2SMe CH(Et)CH.sub.2SMe CH(i-Pr)CH.sub.2SMe
CH(i-Bu)CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2CH(Me)SMe
CH.sub.2CH.sub.2CH(CF.sub.3)SMe CH(Me)CH.sub.2CH.sub.2SMe
CH(Et)CH.sub.2CH.sub.2SMe CH.sub.2CH(Me)CH.sub.2SMe
CH.sub.2C(Me).sub.2CH.sub.2SMe CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2S(O)(i-Pr) CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH(Me)S(O)Me CH.sub.2CH(CF.sub.3)S(O)Me
CH.sub.2C(Me).sub.2S(O)Me CH(Me)CH.sub.2S(O)Me CH(Et)CH.sub.2S(O)Me
CH(i-Bu)CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH.sub.2CH(Me)S(O)Me CH.sub.2CH.sub.2CH(CF.sub.3)S(O)Me
CH(Me)CH.sub.2CH.sub.2S(O)Me CH(Et)CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH(Me)CH.sub.2S(O)Me CH.sub.2C(Me).sub.2CH.sub.2S(O)Me
CH.sub.2(2-pyridinyl) CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2SO.sub.2(i-Pr) CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH(CF.sub.3)SO.sub.2Me CH.sub.2C(Me).sub.2SO.sub.2Me
CH(Me)CH.sub.2SO.sub.2Me C(Me).sub.2CH.sub.2SO.sub.2Me
CH(Et)CH.sub.2SO.sub.2Me CH(i-Pr)CH.sub.2SO.sub.2Me
CH(i-Bu)CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH.sub.2CH(CF.sub.3)SO.sub.2Me
CH(Me)CH.sub.2CH.sub.2SO.sub.2Me CH(Et)CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH(Me)CH.sub.2SO.sub.2Me
CH.sub.2C(Me).sub.2CH.sub.2SO.sub.2Me
CH.sub.2C(O)NHCH.sub.2CH.sub.2F CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl
CH.sub.2C(O)NHCH.sub.2CHF.sub.2 CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me) CH.sub.2C(O)NHCH.sub.2C(Me).sub.2F
CH.sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CHFCF.sub.3
CH.sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH(CF.sub.3).sub.2 CH.sub.2C(O)NHC(Me).sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
CH.sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2F CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)F CH(Me)C(O)NHCH.sub.2C(Me).sub.2F
CH(Me)C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CHFCF.sub.3
CH(Me)C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH(CF.sub.3).sub.2 CH(Me)C(O)NHC(Me).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3
CH(Me)C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)NHCH.sub.2CHF.sub.2
C(Me).sub.2C(O)NHCH.sub.2CF.sub.3 C(Me).sub.2C(O)NHCH.sub.2CH(Me)F
C(Me).sub.2C(O)NHCH.sub.2C(Me).sub.2F
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CHFCF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NH(c-Pr)
CH.sub.2C(O)NH(CH.sub.2--c-Pr) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et) CH.sub.2C(O)NH(n-Pr)
CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(n-Bu) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH.sub.2C(O)NMe.sub.2 CH.sub.2C(O)NMe(Et)
CH.sub.2C(O)NEt.sub.2 CH.sub.2C(O)NMe(n-Pr) CH.sub.2C(O)NMe(i-Pr)
CH.sub.2C(O)NMe(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(n-Bu)
CH(Me)C(O)NH(i-Bu) CH(Me)C(O)NH(s-Bu) C(Me).sub.2C(O)NH(Me)
C(Me).sub.2C(O)NH(Et) C(Me).sub.2C(O)NH(n-Pr)
C(Me).sub.2C(O)NH(i-Pr) (Me).sub.2C(O)NH(n-Bu)
C(Me).sub.2C(O)NH(i-Bu) C(Me).sub.2C(O)NH(s-Bu)
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
CH.sub.2C(O)N(Me)CH.sub.2CHF.sub.2
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH(Me)CF.sub.3 CH.sub.2C(O)N(Me)CH(CF.sub.3).sub.2
CH.sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2F CH(Me)C(O)N(Me)CH.sub.2CH.sub.2Cl
CH(Me)C(O)N(Me)CH.sub.2CHF.sub.2 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH(Me)CF.sub.3 CH(Me)C(O)N(Me)CH(CF.sub.3).sub.2
CH(Me)C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)N(Me)CH.sub.2CHF.sub.2
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH(Me)CF.sub.3
C(Me).sub.2C(O)N(Me)CH(CF.sub.3).sub.2
C(Me).sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(Me)CF.sub.3 C(Me).sub.2C(O)NHCH(CF.sub.3).sub.2
C(Me).sub.2C(O)NHC(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(i-Pr)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) R.sup.1 is CF.sub.3, R.sup.3 is Br
CH.sub.2CH.sub.2OH CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2O(i-Pr) CH.sub.2CH(Me)OH CH.sub.2CH(CF.sub.3)OH
CH.sub.2C(Me).sub.2OH CH.sub.2C(CF.sub.3)(Me)OH CH(Me)CH.sub.2OH
C(Me).sub.2CH.sub.2OH CH(Et)CH.sub.2OH
CH(i-Pr)CH.sub.2OH CH(i-Bu)CH.sub.2OH CH(Me)CH(CF.sub.3)OH
CH.sub.2CH.sub.2CH.sub.2OH CH.sub.2CH.sub.2CH.sub.2OMe
CH.sub.2CH.sub.2CH.sub.2OEt CH.sub.2CH.sub.2CH(CF.sub.3)OH
CH(Me)CH.sub.2CH.sub.2OH CH.sub.2CH(Me)CH.sub.2OH
CH.sub.2C(Me).sub.2CH.sub.2OH CH.sub.2CH.sub.2CH(Me)OH
CH.sub.2CH.sub.2C(Me).sub.2OH CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2S(i-Pr)
CH.sub.2CH.sub.2S(i-Bu) CH.sub.2CH(Me)SMe CH.sub.2CH(CF.sub.3)SMe
CH.sub.2C(Me).sub.2SMe CH(Me)CH.sub.2SMe C(Me).sub.2CH.sub.2SMe
CH(Et)CH.sub.2SMe CH(i-Pr)CH.sub.2SMe CH(i-Bu)CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2CH(Me)SMe CH.sub.2CH.sub.2CH(CF.sub.3)SMe
CH(Me)CH.sub.2CH.sub.2SMe CH(Et)CH.sub.2CH.sub.2SMe
CH.sub.2CH(Me)CH.sub.2SMe CH.sub.2C(Me).sub.2CH.sub.2SMe
CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2S(O)(i-Pr)
CH.sub.2CH.sub.2S(O)(i-Bu) CH.sub.2CH(Me)S(O)Me
CH.sub.2CH(CF.sub.3)S(O)Me CH.sub.2C(Me).sub.2S(O)Me
CH(Me)CH.sub.2S(O)Me CH(Et)CH.sub.2S(O)Me CH(i-Bu)CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2CH.sub.2S(O)(i-Bu) CH.sub.2CH.sub.2CH(Me)S(O)Me
CH.sub.2CH.sub.2CH(CF.sub.3)S(O)Me CH(Me)CH.sub.2CH.sub.2S(O)Me
CH(Et)CH.sub.2CH.sub.2S(O)Me CH.sub.2CH(Me)CH.sub.2S(O)Me
CH.sub.2C(Me).sub.2CH.sub.2S(O)Me CH.sub.2(2-pyridinyl)
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2SO.sub.2(i-Pr)
CH.sub.2CH(Me)SO.sub.2Me CH.sub.2CH(CF.sub.3)SO.sub.2Me
CH.sub.2C(Me).sub.2SO.sub.2Me CH(Me)CH.sub.2SO.sub.2Me
C(Me).sub.2CH.sub.2SO.sub.2Me CH(Et)CH.sub.2SO.sub.2Me
CH(i-Pr)CH.sub.2SO.sub.2Me CH(i-Bu)CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH.sub.2CH(CF.sub.3)SO.sub.2Me
CH(Me)CH.sub.2CH.sub.2SO.sub.2Me CH(Et)CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH(Me)CH.sub.2SO.sub.2Me
CH.sub.2C(Me).sub.2CH.sub.2SO.sub.2Me
CH.sub.2C(O)NHCH.sub.2CH.sub.2F CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl
CH.sub.2C(O)NHCH.sub.2CHF.sub.2 CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me) CH.sub.2C(O)NHCH.sub.2C(Me).sub.2F
CH.sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CHFCF.sub.3
CH.sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH(CF.sub.3).sub.2 CH.sub.2C(O)NHC(Me).sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
CH.sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2F CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)F CH(Me)C(O)NHCH.sub.2C(Me).sub.2F
CH(Me)C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CHFCF.sub.3
CH(Me)C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH(CF.sub.3).sub.2 CH(Me)C(O)NHC(Me).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3
CH(Me)C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)NHCH.sub.2CHF.sub.2
C(Me).sub.2C(O)NHCH.sub.2CF.sub.3 C(Me).sub.2C(O)NHCH.sub.2CH(Me)F
C(Me).sub.2C(O)NHCH.sub.2C(Me).sub.2F
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CHFCF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NH(c-Pr)
CH.sub.2C(O)NH(CH.sub.2--c-Pr) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et) CH.sub.2C(O)NH(n-Pr)
CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(n-Bu) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH.sub.2C(O)NMe.sub.2 CH.sub.2C(O)NMe(Et)
CH.sub.2C(O)NEt.sub.2 CH.sub.2C(O)NMe(n-Pr) CH.sub.2C(O)NMe(i-Pr)
CH.sub.2C(O)NMe(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(n-Bu)
CH(Me)C(O)NH(i-Bu) CH(Me)C(O)NH(s-Bu) C(Me).sub.2C(O)NH(Me)
C(Me).sub.2C(O)NH(Et) C(Me).sub.2C(O)NH(n-Pr)
C(Me).sub.2C(O)NH(i-Pr) (Me).sub.2C(O)NH(n-Bu)
C(Me).sub.2C(O)NH(i-Bu) C(Me).sub.2C(O)NH(s-Bu)
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
CH.sub.2C(O)N(Me)CH.sub.2CHF.sub.2
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH(Me)CF.sub.3 CH.sub.2C(O)N(Me)CH(CF.sub.3).sub.2
CH.sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2F CH(Me)C(O)N(Me)CH.sub.2CH.sub.2Cl
CH(Me)C(O)N(Me)CH.sub.2CHF.sub.2 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH(Me)CF.sub.3 CH(Me)C(O)N(Me)CH(CF.sub.3).sub.2
CH(Me)C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)N(Me)CH.sub.2CHF.sub.2
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH(Me)CF.sub.3
C(Me).sub.2C(O)N(Me)CH(CF.sub.3).sub.2
C(Me).sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(Me)CF.sub.3 C(Me).sub.2C(O)NHCH(CF.sub.3).sub.2
C(Me).sub.2C(O)NHC(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(i-Pr)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) R.sup.1 is CF.sub.3, R.sup.3 is
CF.sub.3 CH.sub.2CH.sub.2OH CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2O(i-Pr) CH.sub.2CH(Me)OH CH.sub.2CH(CF.sub.3)OH
CH.sub.2C(Me).sub.2OH CH.sub.2C(CF.sub.3)(Me)OH CH(Me)CH.sub.2OH
C(Me).sub.2CH.sub.2OH CH(Et)CH.sub.2OH CH(i-Pr)CH.sub.2OH
CH(i-Bu)CH.sub.2OH CH(Me)CH(CF.sub.3)OH CH.sub.2CH.sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2CH(CF.sub.3)OH CH(Me)CH.sub.2CH.sub.2OH
CH.sub.2CH(Me)CH.sub.2OH CH.sub.2C(Me).sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH(Me)OH CH.sub.2CH.sub.2C(Me).sub.2OH
CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2S(i-Pr) CH.sub.2CH.sub.2S(i-Bu) CH.sub.2CH(Me)SMe
CH.sub.2CH(CF.sub.3)SMe CH.sub.2C(Me).sub.2SMe CH(Me)CH.sub.2SMe
C(Me).sub.2CH.sub.2SMe CH(Et)CH.sub.2SMe CH(i-Pr)CH.sub.2SMe
CH(i-Bu)CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2CH(Me)SMe
CH.sub.2CH.sub.2CH(CF.sub.3)SMe CH(Me)CH.sub.2CH.sub.2SMe
CH(Et)CH.sub.2CH.sub.2SMe CH.sub.2CH(Me)CH.sub.2SMe
CH.sub.2C(Me).sub.2CH.sub.2SMe CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2S(O)(i-Pr) CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH(Me)S(O)Me CH.sub.2CH(CF.sub.3)S(O)Me
CH.sub.2C(Me).sub.2S(O)Me CH(Me)CH.sub.2S(O)Me CH(Et)CH.sub.2S(O)Me
CH(i-Bu)CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH.sub.2CH(Me)S(O)Me CH.sub.2CH.sub.2CH(CF.sub.3)S(O)Me
CH(Me)CH.sub.2CH.sub.2S(O)Me CH(Et)CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH(Me)CH.sub.2S(O)Me CH.sub.2C(Me).sub.2CH.sub.2S(O)Me
CH.sub.2(2-pyridinyl)
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2SO.sub.2(i-Pr)
CH.sub.2CH(Me)SO.sub.2Me CH.sub.2CH(CF.sub.3)SO.sub.2Me
CH.sub.2C(Me).sub.2SO.sub.2Me CH(Me)CH.sub.2SO.sub.2Me
C(Me).sub.2CH.sub.2SO.sub.2Me CH(Et)CH.sub.2SO.sub.2Me
CH(i-Pr)CH.sub.2SO.sub.2Me CH(i-Bu)CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH.sub.2CH(CF.sub.3)SO.sub.2Me
CH(Me)CH.sub.2CH.sub.2SO.sub.2Me CH(Et)CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH(Me)CH.sub.2SO.sub.2Me
CH.sub.2C(Me).sub.2CH.sub.2SO.sub.2Me
CH.sub.2C(O)NHCH.sub.2CH.sub.2F CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl
CH.sub.2C(O)NHCH.sub.2CHF.sub.2 CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me) CH.sub.2C(O)NHCH.sub.2C(Me).sub.2F
CH.sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CHFCF.sub.3
CH.sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH(CF.sub.3).sub.2 CH.sub.2C(O)NHC(Me).sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
CH.sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2F CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)F CH(Me)C(O)NHCH.sub.2C(Me).sub.2F
CH(Me)C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CHFCF.sub.3
CH(Me)C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH(CF.sub.3).sub.2 CH(Me)C(O)NHC(Me).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3
CH(Me)C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)NHCH.sub.2CHF.sub.2
C(Me).sub.2C(O)NHCH.sub.2CF.sub.3 C(Me).sub.2C(O)NHCH.sub.2CH(Me)F
C(Me).sub.2C(O)NHCH.sub.2C(Me).sub.2F
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CHFCF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NH(c-Pr)
CH.sub.2C(O)NH(CH.sub.2--c-Pr) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et) CH.sub.2C(O)NH(n-Pr)
CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(n-Bu) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH.sub.2C(O)NMe.sub.2 CH.sub.2C(O)NMe(Et)
CH.sub.2C(O)NEt.sub.2 CH.sub.2C(O)NMe(n-Pr) CH.sub.2C(O)NMe(i-Pr)
CH.sub.2C(O)NMe(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(n-Bu)
CH(Me)C(O)NH(i-Bu) CH(Me)C(O)NH(s-Bu) C(Me).sub.2C(O)NH(Me)
C(Me).sub.2C(O)NH(Et) C(Me).sub.2C(O)NH(n-Pr)
C(Me).sub.2C(O)NH(i-Pr) (Me).sub.2C(O)NH(n-Bu)
C(Me).sub.2C(O)NH(i-Bu) C(Me).sub.2C(O)NH(s-Bu)
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
CH.sub.2C(O)N(Me)CH.sub.2CHF.sub.2
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH(Me)CF.sub.3 CH.sub.2C(O)N(Me)CH(CF.sub.3).sub.2
CH.sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2F CH(Me)C(O)N(Me)CH.sub.2CH.sub.2Cl
CH(Me)C(O)N(Me)CH.sub.2CHF.sub.2 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH(Me)CF.sub.3 CH(Me)C(O)N(Me)CH(CF.sub.3).sub.2
CH(Me)C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)N(Me)CH.sub.2CHF.sub.2
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH(Me)CF.sub.3
C(Me).sub.2C(O)N(Me)CH(CF.sub.3).sub.2
C(Me).sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(Me)CF.sub.3 C(Me).sub.2C(O)NHCH(CF.sub.3).sub.2
C(Me).sub.2C(O)NHC(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(i-Pr)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) R.sup.1 is OCF.sub.3, R.sup.3 is Cl
CH.sub.2CH.sub.2OH CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2O(i-Pr) CH.sub.2CH(Me)OH CH.sub.2CH(CF.sub.3)OH
CH.sub.2C(Me).sub.2OH CH.sub.2C(CF.sub.3)(Me)OH CH(Me)CH.sub.2OH
C(Me).sub.2CH.sub.2OH CH(Et)CH.sub.2OH CH(i-Pr)CH.sub.2OH
CH(i-Bu)CH.sub.2OH CH(Me)CH(CF.sub.3)OH CH.sub.2CH.sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2CH(CF.sub.3)OH CH(Me)CH.sub.2CH.sub.2OH
CH.sub.2CH(Me)CH.sub.2OH CH.sub.2C(Me).sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH(Me)OH CH.sub.2CH.sub.2C(Me).sub.2OH
CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2S(i-Pr) CH.sub.2CH.sub.2S(i-Bu) CH.sub.2CH(Me)SMe
CH.sub.2CH(CF.sub.3)SMe CH.sub.2C(Me).sub.2SMe CH(Me)CH.sub.2SMe
C(Me).sub.2CH.sub.2SMe CH(Et)CH.sub.2SMe CH(i-Pr)CH.sub.2SMe
CH(i-Bu)CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2CH(Me)SMe
CH.sub.2CH.sub.2CH(CF.sub.3)SMe CH(Me)CH.sub.2CH.sub.2SMe
CH(Et)CH.sub.2CH.sub.2SMe CH.sub.2CH(Me)CH.sub.2SMe
CH.sub.2C(Me).sub.2CH.sub.2SMe CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2S(O)(i-Pr) CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH(Me)S(O)Me CH.sub.2CH(CF.sub.3)S(O)Me
CH.sub.2C(Me).sub.2S(O)Me CH(Me)CH.sub.2S(O)Me CH(Et)CH.sub.2S(O)Me
CH(i-Bu)CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH.sub.2CH(Me)S(O)Me CH.sub.2CH.sub.2CH(CF.sub.3)S(O)Me
CH(Me)CH.sub.2CH.sub.2S(O)Me CH(Et)CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH(Me)CH.sub.2S(O)Me CH.sub.2C(Me).sub.2CH.sub.2S(O)Me
CH.sub.2(2-pyridinyl) CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2SO.sub.2(i-Pr) CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH(CF.sub.3)SO.sub.2Me CH.sub.2C(Me).sub.2SO.sub.2Me
CH(Me)CH.sub.2SO.sub.2Me C(Me).sub.2CH.sub.2SO.sub.2Me
CH(Et)CH.sub.2SO.sub.2Me CH(i-Pr)CH.sub.2SO.sub.2Me
CH(i-Bu)CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH.sub.2CH(CF.sub.3)SO.sub.2Me
CH(Me)CH.sub.2CH.sub.2SO.sub.2Me CH(Et)CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH(Me)CH.sub.2SO.sub.2Me
CH.sub.2C(Me).sub.2CH.sub.2SO.sub.2Me
CH.sub.2C(O)NHCH.sub.2CH.sub.2F CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl
CH.sub.2C(O)NHCH.sub.2CHF.sub.2 CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me) CH.sub.2C(O)NHCH.sub.2C(Me).sub.2F
CH.sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CHFCF.sub.3
CH.sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH(CF.sub.3).sub.2 CH.sub.2C(O)NHC(Me).sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
CH.sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2F CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)F CH(Me)C(O)NHCH.sub.2C(Me).sub.2F
CH(Me)C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CHFCF.sub.3
CH(Me)C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH(CF.sub.3).sub.2 CH(Me)C(O)NHC(Me).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3
CH(Me)C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)NHCH.sub.2CHF.sub.2
C(Me).sub.2C(O)NHCH.sub.2CF.sub.3 C(Me).sub.2C(O)NHCH.sub.2CH(Me)F
C(Me).sub.2C(O)NHCH.sub.2C(Me).sub.2F
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CHFCF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NH(c-Pr)
CH.sub.2C(O)NH(CH.sub.2--c-Pr) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et) CH.sub.2C(O)NH(n-Pr)
CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(n-Bu) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH.sub.2C(O)NMe.sub.2 CH.sub.2C(O)NMe(Et)
CH.sub.2C(O)NEt.sub.2 CH.sub.2C(O)NMe(n-Pr) CH.sub.2C(O)NMe(i-Pr)
CH.sub.2C(O)NMe(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(n-Bu)
CH(Me)C(O)NH(i-Bu) CH(Me)C(O)NH(s-Bu) C(Me).sub.2C(O)NH(Me)
C(Me).sub.2C(O)NH(Et) C(Me).sub.2C(O)NH(n-Pr)
C(Me).sub.2C(O)NH(i-Pr) (Me).sub.2C(O)NH(n-Bu)
C(Me).sub.2C(O)NH(i-Bu) C(Me).sub.2C(O)NH(s-Bu)
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
CH.sub.2C(O)N(Me)CH.sub.2CHF.sub.2
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH(Me)CF.sub.3 CH.sub.2C(O)N(Me)CH(CF.sub.3).sub.2
CH.sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2F CH(Me)C(O)N(Me)CH.sub.2CH.sub.2Cl
CH(Me)C(O)N(Me)CH.sub.2CHF.sub.2 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH(Me)CF.sub.3 CH(Me)C(O)N(Me)CH(CF.sub.3).sub.2
CH(Me)C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)N(Me)CH.sub.2CHF.sub.2
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH(Me)CF.sub.3
C(Me).sub.2C(O)N(Me)CH(CF.sub.3).sub.2
C(Me).sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(Me)CF.sub.3 C(Me).sub.2C(O)NHCH(CF.sub.3).sub.2
C(Me).sub.2C(O)NHC(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(i-Pr)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) R.sup.1 is OCH.sub.2CF.sub.3, R.sup.3
is F CH.sub.2CH.sub.2OH CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2O(i-Pr) CH.sub.2CH(Me)OH CH.sub.2CH(CF.sub.3)OH
CH.sub.2C(Me).sub.2OH CH.sub.2C(CF.sub.3)(Me)OH CH(Me)CH.sub.2OH
C(Me).sub.2CH.sub.2OH CH(Et)CH.sub.2OH CH(i-Pr)CH.sub.2OH
CH(i-Bu)CH.sub.2OH CH(Me)CH(CF.sub.3)OH CH.sub.2CH.sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2CH(CF.sub.3)OH CH(Me)CH.sub.2CH.sub.2OH
CH.sub.2CH(Me)CH.sub.2OH CH.sub.2C(Me).sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH(Me)OH CH.sub.2CH.sub.2C(Me).sub.2OH
CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2S(i-Pr) CH.sub.2CH.sub.2S(i-Bu) CH.sub.2CH(Me)SMe
CH.sub.2CH(CF.sub.3)SMe CH.sub.2C(Me).sub.2SMe CH(Me)CH.sub.2SMe
C(Me).sub.2CH.sub.2SMe CH(Et)CH.sub.2SMe CH(i-Pr)CH.sub.2SMe
CH(i-Bu)CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2CH(Me)SMe
CH.sub.2CH.sub.2CH(CF.sub.3)SMe CH(Me)CH.sub.2CH.sub.2SMe
CH(Et)CH.sub.2CH.sub.2SMe CH.sub.2CH(Me)CH.sub.2SMe
CH.sub.2C(Me).sub.2CH.sub.2SMe CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2S(O)(i-Pr) CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH(Me)S(O)Me CH.sub.2CH(CF.sub.3)S(O)Me
CH.sub.2C(Me).sub.2S(O)Me CH(Me)CH.sub.2S(O)Me CH(Et)CH.sub.2S(O)Me
CH(i-Bu)CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH.sub.2CH(Me)S(O)Me CH.sub.2CH.sub.2CH(CF.sub.3)S(O)Me
CH(Me)CH.sub.2CH.sub.2S(O)Me CH(Et)CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH(Me)CH.sub.2S(O)Me CH.sub.2C(Me).sub.2CH.sub.2S(O)Me
CH.sub.2(2-pyridinyl) CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2SO.sub.2(i-Pr) CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH(CF.sub.3)SO.sub.2Me CH.sub.2C(Me).sub.2SO.sub.2Me
CH(Me)CH.sub.2SO.sub.2Me C(Me).sub.2CH.sub.2SO.sub.2Me
CH(Et)CH.sub.2SO.sub.2Me CH(i-Pr)CH.sub.2SO.sub.2Me
CH(i-Bu)CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH.sub.2CH(CF.sub.3)SO.sub.2Me
CH(Me)CH.sub.2CH.sub.2SO.sub.2Me CH(Et)CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH(Me)CH.sub.2SO.sub.2Me
CH.sub.2C(Me).sub.2CH.sub.2SO.sub.2Me
CH.sub.2C(O)NHCH.sub.2CH.sub.2F CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl
CH.sub.2C(O)NHCH.sub.2CHF.sub.2 CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me) CH.sub.2C(O)NHCH.sub.2C(Me).sub.2F
CH.sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CHFCF.sub.3
CH.sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH(CF.sub.3).sub.2 CH.sub.2C(O)NHC(Me).sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
CH.sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2F CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)F CH(Me)C(O)NHCH.sub.2C(Me).sub.2F
CH(Me)C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CHFCF.sub.3
CH(Me)C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH(CF.sub.3).sub.2 CH(Me)C(O)NHC(Me).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3
CH(Me)C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)NHCH.sub.2CHF.sub.2
C(Me).sub.2C(O)NHCH.sub.2CF.sub.3 C(Me).sub.2C(O)NHCH.sub.2CH(Me)F
C(Me).sub.2C(O)NHCH.sub.2C(Me).sub.2F
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CHFCF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NH(c-Pr)
CH.sub.2C(O)NH(CH.sub.2--c-Pr) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et) CH.sub.2C(O)NH(n-Pr)
CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(n-Bu) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH.sub.2C(O)NMe.sub.2 CH.sub.2C(O)NMe(Et)
CH.sub.2C(O)NEt.sub.2 CH.sub.2C(O)NMe(n-Pr) CH.sub.2C(O)NMe(i-Pr)
CH.sub.2C(O)NMe(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(n-Bu)
CH(Me)C(O)NH(i-Bu) CH(Me)C(O)NH(s-Bu) C(Me).sub.2C(O)NH(Me)
C(Me).sub.2C(O)NH(Et) C(Me).sub.2C(O)NH(n-Pr)
C(Me).sub.2C(O)NH(i-Pr) (Me).sub.2C(O)NH(n-Bu)
C(Me).sub.2C(O)NH(i-Bu) C(Me).sub.2C(O)NH(s-Bu)
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
CH.sub.2C(O)N(Me)CH.sub.2CHF.sub.2
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH(Me)CF.sub.3 CH.sub.2C(O)N(Me)CH(CF.sub.3).sub.2
CH.sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2F CH(Me)C(O)N(Me)CH.sub.2CH.sub.2Cl
CH(Me)C(O)N(Me)CH.sub.2CHF.sub.2 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH(Me)CF.sub.3 CH(Me)C(O)N(Me)CH(CF.sub.3).sub.2
CH(Me)C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)N(Me)CH.sub.2CHF.sub.2
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH(Me)CF.sub.3
C(Me).sub.2C(O)N(Me)CH(CF.sub.3).sub.2
C(Me).sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(Me)CF.sub.3 C(Me).sub.2C(O)NHCH(CF.sub.3).sub.2
C(Me).sub.2C(O)NHC(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(i-Pr)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) R.sup.1 is OCH.sub.2CF.sub.3, R.sup.3
is Cl CH.sub.2CH.sub.2OH CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2O(i-Pr) CH.sub.2CH(Me)OH CH.sub.2CH(CF.sub.3)OH
CH.sub.2C(Me).sub.2OH CH.sub.2C(CF.sub.3)(Me)OH CH(Me)CH.sub.2OH
C(Me).sub.2CH.sub.2OH CH(Et)CH.sub.2OH CH(i-Pr)CH.sub.2OH
CH(i-Bu)CH.sub.2OH CH(Me)CH(CF.sub.3)OH CH.sub.2CH.sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2CH(CF.sub.3)OH CH(Me)CH.sub.2CH.sub.2OH
CH.sub.2CH(Me)CH.sub.2OH CH.sub.2C(Me).sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH(Me)OH CH.sub.2CH.sub.2C(Me).sub.2OH
CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2S(i-Pr) CH.sub.2CH.sub.2S(i-Bu) CH.sub.2CH(Me)SMe
CH.sub.2CH(CF.sub.3)SMe CH.sub.2C(Me).sub.2SMe CH(Me)CH.sub.2SMe
C(Me).sub.2CH.sub.2SMe CH(Et)CH.sub.2SMe CH(i-Pr)CH.sub.2SMe
CH(i-Bu)CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2CH(Me)SMe
CH.sub.2CH.sub.2CH(CF.sub.3)SMe CH(Me)CH.sub.2CH.sub.2SMe
CH(Et)CH.sub.2CH.sub.2SMe CH.sub.2CH(Me)CH.sub.2SMe
CH.sub.2C(Me).sub.2CH.sub.2SMe CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2S(O)(i-Pr) CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH(Me)S(O)Me CH.sub.2CH(CF.sub.3)S(O)Me
CH.sub.2C(Me).sub.2S(O)Me CH(Me)CH.sub.2S(O)Me CH(Et)CH.sub.2S(O)Me
CH(i-Bu)CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2CH.sub.2S(O)(i-Bu)
CH.sub.2CH.sub.2CH(Me)S(O)Me CH.sub.2CH.sub.2CH(CF.sub.3)S(O)Me
CH(Me)CH.sub.2CH.sub.2S(O)Me CH(Et)CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH(Me)CH.sub.2S(O)Me CH.sub.2C(Me).sub.2CH.sub.2S(O)Me
CH.sub.2(2-pyridinyl) CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2SO.sub.2(i-Pr) CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH(CF.sub.3)SO.sub.2Me CH.sub.2C(Me).sub.2SO.sub.2Me
CH(Me)CH.sub.2SO.sub.2Me C(Me).sub.2CH.sub.2SO.sub.2Me
CH(Et)CH.sub.2SO.sub.2Me CH(i-Pr)CH.sub.2SO.sub.2Me
CH(i-Bu)CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH.sub.2CH(CF.sub.3)SO.sub.2Me
CH(Me)CH.sub.2CH.sub.2SO.sub.2Me CH(Et)CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH(Me)CH.sub.2SO.sub.2Me
CH.sub.2C(Me).sub.2CH.sub.2SO.sub.2Me
CH.sub.2C(O)NHCH.sub.2CH.sub.2F CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl
CH.sub.2C(O)NHCH.sub.2CHF.sub.2 CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me) CH.sub.2C(O)NHCH.sub.2C(Me).sub.2F
CH.sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CHFCF.sub.3
CH.sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH(CF.sub.3).sub.2 CH.sub.2C(O)NHC(Me).sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
CH.sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2F CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)F CH(Me)C(O)NHCH.sub.2C(Me).sub.2F
CH(Me)C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CHFCF.sub.3
CH(Me)C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH(CF.sub.3).sub.2 CH(Me)C(O)NHC(Me).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3
CH(Me)C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)NHCH.sub.2CHF.sub.2
C(Me).sub.2C(O)NHCH.sub.2CF.sub.3 C(Me).sub.2C(O)NHCH.sub.2CH(Me)F
C(Me).sub.2C(O)NHCH.sub.2C(Me).sub.2F
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CHFCF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NH(c-Pr)
CH.sub.2C(O)NH(CH.sub.2--c-Pr) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et) CH.sub.2C(O)NH(n-Pr)
CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(n-Bu) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH.sub.2C(O)NMe.sub.2 CH.sub.2C(O)NMe(Et)
CH.sub.2C(O)NEt.sub.2 CH.sub.2C(O)NMe(n-Pr) CH.sub.2C(O)NMe(i-Pr)
CH.sub.2C(O)NMe(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(n-Bu)
CH(Me)C(O)NH(i-Bu) CH(Me)C(O)NH(s-Bu) C(Me).sub.2C(O)NH(Me)
C(Me).sub.2C(O)NH(Et) C(Me).sub.2C(O)NH(n-Pr)
C(Me).sub.2C(O)NH(i-Pr) (Me).sub.2C(O)NH(n-Bu)
C(Me).sub.2C(O)NH(i-Bu) C(Me).sub.2C(O)NH(s-Bu)
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
CH.sub.2C(O)N(Me)CH.sub.2CHF.sub.2
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH(Me)CF.sub.3 CH.sub.2C(O)N(Me)CH(CF.sub.3).sub.2
CH.sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2F CH(Me)C(O)N(Me)CH.sub.2CH.sub.2Cl
CH(Me)C(O)N(Me)CH.sub.2CHF.sub.2 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH(Me)CF.sub.3 CH(Me)C(O)N(Me)CH(CF.sub.3).sub.2
CH(Me)C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)N(Me)CH.sub.2CHF.sub.2
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH(Me)CF.sub.3
C(Me).sub.2C(O)N(Me)CH(CF.sub.3).sub.2
C(Me).sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(Me)CF.sub.3 C(Me).sub.2C(O)NHCH(CF.sub.3).sub.2
C(Me).sub.2C(O)NHC(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(i-Pr)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) R.sup.1 is OCH.sub.2CF.sub.3, R.sup.3
is Br CH.sub.2CH.sub.2OH CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2O(i-Pr) CH.sub.2CH(Me)OH CH.sub.2CH(CF.sub.3)OH
CH.sub.2C(Me).sub.2OH CH.sub.2C(CF.sub.3)(Me)OH CH(Me)CH.sub.2OH
C(Me).sub.2CH.sub.2OH CH(Et)CH.sub.2OH CH(i-Pr)CH.sub.2OH
CH(i-Bu)CH.sub.2OH CH(Me)CH(CF.sub.3)OH CH.sub.2CH.sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH.sub.2OMe CH.sub.2CH.sub.2CH.sub.2OEt
CH.sub.2CH.sub.2CH(CF.sub.3)OH CH(Me)CH.sub.2CH.sub.2OH
CH.sub.2CH(Me)CH.sub.2OH CH.sub.2C(Me).sub.2CH.sub.2OH
CH.sub.2CH.sub.2CH(Me)OH CH.sub.2CH.sub.2C(Me).sub.2OH
CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2S(i-Pr) CH.sub.2CH.sub.2S(i-Bu) CH.sub.2CH(Me)SMe
CH.sub.2CH(CF.sub.3)SMe
CH.sub.2C(Me).sub.2SMe CH(Me)CH.sub.2SMe C(Me).sub.2CH.sub.2SMe
CH(Et)CH.sub.2SMe CH(i-Pr)CH.sub.2SMe CH(i-Bu)CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2CH(Me)SMe CH.sub.2CH.sub.2CH(CF.sub.3)SMe
CH(Me)CH.sub.2CH.sub.2SMe CH(Et)CH.sub.2CH.sub.2SMe
CH.sub.2CH(Me)CH.sub.2SMe CH.sub.2C(Me).sub.2CH.sub.2SMe
CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2S(O)(i-Pr)
CH.sub.2CH.sub.2S(O)(i-Bu) CH.sub.2CH(Me)S(O)Me
CH.sub.2CH(CF.sub.3)S(O)Me CH.sub.2C(Me).sub.2S(O)Me
CH(Me)CH.sub.2S(O)Me CH(Et)CH.sub.2S(O)Me CH(i-Bu)CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2CH.sub.2S(O)(i-Bu) CH.sub.2CH.sub.2CH(Me)S(O)Me
CH.sub.2CH.sub.2CH(CF.sub.3)S(O)Me CH(Me)CH.sub.2CH.sub.2S(O)Me
CH(Et)CH.sub.2CH.sub.2S(O)Me CH.sub.2CH(Me)CH.sub.2S(O)Me
CH.sub.2C(Me).sub.2CH.sub.2S(O)Me CH.sub.2(2-pyridinyl)
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2SO.sub.2(i-Pr)
CH.sub.2CH(Me)SO.sub.2Me CH.sub.2CH(CF.sub.3)SO.sub.2Me
CH.sub.2C(Me).sub.2SO.sub.2Me CH(Me)CH.sub.2SO.sub.2Me
C(Me).sub.2CH.sub.2SO.sub.2Me CH(Et)CH.sub.2SO.sub.2Me
CH(i-Pr)CH.sub.2SO.sub.2Me CH(i-Bu)CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2CH(Me)SO.sub.2Me
CH.sub.2CH.sub.2CH(CF.sub.3)SO.sub.2Me
CH(Me)CH.sub.2CH.sub.2SO.sub.2Me CH(Et)CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH(Me)CH.sub.2SO.sub.2Me
CH.sub.2C(Me).sub.2CH.sub.2SO.sub.2Me
CH.sub.2C(O)NHCH.sub.2CH.sub.2F CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl
CH.sub.2C(O)NHCH.sub.2CHF.sub.2 CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me) CH.sub.2C(O)NHCH.sub.2C(Me).sub.2F
CH.sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CHFCF.sub.3
CH.sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH(CF.sub.3).sub.2 CH.sub.2C(O)NHC(Me).sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
CH.sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2F CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)F CH(Me)C(O)NHCH.sub.2C(Me).sub.2F
CH(Me)C(O)NH(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CHFCF.sub.3
CH(Me)C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH(CF.sub.3).sub.2 CH(Me)C(O)NHC(Me).sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3
CH(Me)C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)NHCH.sub.2CHF.sub.2
C(Me).sub.2C(O)NHCH.sub.2CF.sub.3 C(Me).sub.2C(O)NHCH.sub.2CH(Me)F
C(Me).sub.2C(O)NHCH.sub.2C(Me).sub.2F
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CH.sub.2F
C(Me).sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CHFCF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CF.sub.2CF.sub.3 CH.sub.2C(O)NH(c-Pr)
CH.sub.2C(O)NH(CH.sub.2--c-Pr) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et) CH.sub.2C(O)NH(n-Pr)
CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(n-Bu) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH.sub.2C(O)NMe.sub.2 CH.sub.2C(O)NMe(Et)
CH.sub.2C(O)NEt.sub.2 CH.sub.2C(O)NMe(n-Pr) CH.sub.2C(O)NMe(i-Pr)
CH.sub.2C(O)NMe(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(n-Bu)
CH(Me)C(O)NH(i-Bu) CH(Me)C(O)NH(s-Bu) C(Me).sub.2C(O)NH(Me)
C(Me).sub.2C(O)NH(Et) C(Me).sub.2C(O)NH(n-Pr)
C(Me).sub.2C(O)NH(i-Pr) (Me).sub.2C(O)NH(n-Bu)
C(Me).sub.2C(O)NH(i-Bu) C(Me).sub.2C(O)NH(s-Bu)
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
CH.sub.2C(O)N(Me)CH.sub.2CHF.sub.2
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
CH.sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH.sub.2C(O)N(Me)CH(Me)CF.sub.3 CH.sub.2C(O)N(Me)CH(CF.sub.3).sub.2
CH.sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2F CH(Me)C(O)N(Me)CH.sub.2CH.sub.2Cl
CH(Me)C(O)N(Me)CH.sub.2CHF.sub.2 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)(CH.sub.2).sub.2CH.sub.2F
CH(Me)C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
CH(Me)C(O)N(Me)CH(Me)CF.sub.3 CH(Me)C(O)N(Me)CH(CF.sub.3).sub.2
CH(Me)C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2Cl
C(Me).sub.2C(O)N(Me)CH.sub.2CHF.sub.2
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CH.sub.2F
C(Me).sub.2C(O)N(Me)CH.sub.2CH.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH.sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)N(Me)CH(Me)CF.sub.3
C(Me).sub.2C(O)N(Me)CH(CF.sub.3).sub.2
C(Me).sub.2C(O)N(Me)C(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(Me)CF.sub.3 C(Me).sub.2C(O)NHCH(CF.sub.3).sub.2
C(Me).sub.2C(O)NHC(Me).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3
C(Me).sub.2C(O)NH(CH.sub.2).sub.2CF.sub.2CF.sub.3
C(Me).sub.2C(O)NHCH.sub.2(CF.sub.2).sub.2CF.sub.3
C(Me).sub.2C(O)NHCH(i-Pr)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr)
TABLE-US-00006 TABLE 4 ##STR00012## R.sup.6 R.sup.1 is Cl, R.sup.3
is Cl CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is Br, R.sup.3 is Br
CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is CF.sub.3, R.sup.3 is
H CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is CF.sub.3, R.sup.3 is
F CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is CF.sub.3, R.sup.3 is
Cl CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is CF.sub.3, R.sup.3 is
Br CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is CF.sub.3, R.sup.3 is
CF.sub.3 CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is OCF.sub.3, R.sup.3 is
Cl CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2S(O)(n-Pr) CH.sub.2CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2CH.sub.2SO.sub.2(n-Pr)
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is OCH.sub.2CF.sub.3,
R.sup.3 is F CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is OCH.sub.2CF.sub.3,
R.sup.3 is Cl CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3 R.sup.1 is OCH.sub.2CF.sub.3,
R.sup.3 is Br CH.sub.2CH.sub.2SMe CH.sub.2CH.sub.2SEt
CH.sub.2CH.sub.2S(n-Pr) CH.sub.2CH.sub.2CH.sub.2SMe
CH.sub.2CH.sub.2CH.sub.2SEt CH.sub.2CH.sub.2S(O)Me
CH.sub.2CH.sub.2S(O)Et CH.sub.2CH.sub.2S(O)(n-Pr)
CH.sub.2CH.sub.2CH.sub.2S(O)Me CH.sub.2CH.sub.2CH.sub.2S(O)Et
CH.sub.2CH.sub.2SO.sub.2Me CH.sub.2CH.sub.2SO.sub.2Et
CH.sub.2CH.sub.2SO.sub.2(n-Pr) CH.sub.2CH.sub.2CH.sub.2SO.sub.2Me
CH.sub.2CH.sub.2CH.sub.2SO.sub.2Et CH.sub.2(2-pyridinyl)
CH.sub.2C(O)NH.sub.2 CH.sub.2C(O)NH(Me) CH.sub.2C(O)NH(Et)
CH.sub.2C(O)NH(n-Pr) CH.sub.2C(O)NH(i-Pr) CH.sub.2C(O)NH(i-Bu)
CH.sub.2C(O)NH(s-Bu) CH(Me)C(O)NH(Me) CH(Me)C(O)NH(Et)
CH(Me)C(O)NH(n-Pr) CH(Me)C(O)NH(i-Pr) CH(Me)C(O)NH(i-Bu)
CH(Me)C(O)NH(s-Bu) CH.sub.2(4-thiazolyl)
CH.sub.2C(O)N(Me)CH.sub.2CF.sub.3 CH(Me)C(O)N(Me)CH.sub.2CF.sub.3
CH.sub.2C(O)NH(c-Pr) CH.sub.2C(O)NH(CH.sub.2--c-Pr)
CH.sub.2C(O)NHCH.sub.2CH.sub.2Cl CH.sub.2C(O)NHCH.sub.2CHF.sub.2
CH.sub.2C(O)NHCH.sub.2CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH.sub.2C(O)NHCH(Me)CF.sub.3
CH.sub.2C(O)NHCH.sub.2CH(Me)CF.sub.3 CH(Me)C(O)NH(c-Pr)
CH(Me)C(O)NH(CH.sub.2--c-Pr) CH(Me)C(O)NHCH.sub.2CH.sub.2Cl
CH(Me)C(O)NHCH.sub.2CHF.sub.2 CH(Me)C(O)NHCH.sub.2CF.sub.3
CH(Me)C(O)NHCH.sub.2CH.sub.2CF.sub.3 CH(Me)C(O)NHCH(Me)CF.sub.3
CH(Me)C(O)NHCH.sub.2CH(Me)CF.sub.3
[0212] Compositions of Formula 1 compounds may also contain
formulation auxiliaries and additives, known to those skilled in
the art as formulation aids (some of which may be considered to
also function as solid diluents, liquid diluents or surfactants).
Such formulation auxiliaries and additives may control: pH
(buffers), foaming during processing (antifoams such
polyorganosiloxanes), sedimentation of active ingredients
(suspending agents), viscosity (thixotropic thickeners),
in-container microbial growth (antimicrobials), product freezing
(antifreezes), color (dyes/pigment dispersions), wash-off (film
formers or stickers), evaporation (evaporation retardants), and
other formulation attributes. Film formers include, for example,
polyvinyl acetates, polyvinyl acetate copolymers,
polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols,
polyvinyl alcohol copolymers and waxes. Examples of formulation
auxiliaries and additives include those listed in McCutcheon's
Volume 2: Functional Materials, annual International and North
American editions published by McCutcheon's Division, The
Manufacturing Confectioner Publishing Co.; and PCT Publication WO
03/024222.
[0213] Of note is the present method using a combination of a
compound of Formula 1 with at least one other parasitic
invertebrate pest control active ingredient. Of particular note is
such a method where the other parasitic invertebrate pest control
active ingredient has a different site of action from the compound
of Formula 1. In certain instances, a combination with at least one
other parasitic invertebrate pest control active ingredient having
a similar spectrum of control but a different site of action will
be particularly advantageous for resistance management. Thus, a
composition comprising a compound of Formula 1 useful in the
present method can further comprise a biologically effective amount
of at least one additional parasitic invertebrate pest control
active ingredient having a similar spectrum of control but a
different site of action.
[0214] The compounds of Formula 1 can be applied without other
adjuvants, but most often application will be of a formulation
comprising one or more active ingredients with suitable carriers,
diluents, and surfactants and possibly in combination with a food
depending on the contemplated end use. One method of application
involves spraying a water dispersion or refined oil solution of a
compound of Formula 1. Combinations with spray oils, spray oil
concentrations, spreader stickers, adjuvants, other solvents, and
synergists such as piperonyl butoxide often enhance compound
efficacy. Such sprays can be applied from spray containers such as
a can, a bottle or other container, either by means of a pump or by
releasing it from a pressurized container, e.g., a pressurized
aerosol spray can. Such spray compositions can take various forms,
for example, sprays, mists, foams, fumes or fog. Such spray
compositions thus can further comprise propellants, foaming agents,
etc. as the case may be. Of note is a spray composition comprising
a biologically effective amount of a compound or a composition of
Formula 1 and a carrier. One embodiment of such a spray composition
comprises a biologically effective amount of a compound or a
composition of Formula 1 and a propellant. Representative
propellants include, but are not limited to, methane, ethane,
propane, butane, isobutane, butene, pentane, isopentane,
neopentane, pentene, hydrofluorocarbons, chlorofluorocarbons,
dimethyl ether, and mixtures of the foregoing. Of note is a spray
composition (and a method utilizing such a spray composition
dispensed from a spray container) used to control at least one
parasitic invertebrate pest selected from the group consisting of
mosquitoes, black flies, stable flies, deer flies, horse flies,
wasps, yellow jackets, hornets, ticks, spiders, ants, gnats, and
the like, including individually or in combinations.
[0215] The controlling of animal parasites includes controlling
external parasites that are parasitic to the surface of the body of
the host animal (e.g., shoulders, armpits, abdomen, inner part of
the thighs) and internal parasites that are parasitic to the inside
of the body of the host animal (e.g., stomach, intestine, lung,
veins, under the skin, lymphatic tissue). External parasitic or
disease transmitting pests include, for example, chiggers, ticks,
lice, mosquitoes, flies, mites and fleas. Internal parasites
include heartworms, hookworms and helminths. Compounds and
compositions of Formula 1 are particularly suitable for combating
external parasitic pests. Compounds and compositions of Formula 1
are suitable for systemic and/or non-systemic control of
infestation or infection by parasites on animals.
[0216] Compounds and compositions of Formula 1 are suitable for
combating parasitic invertebrate pests that infest animal subjects
including those in the wild, livestock and agricultural working
animals. Livestock is the term used to refer (singularly or
plurally) to a domesticated animal intentionally reared in an
agricultural setting to make produce such as food or fiber, or for
its labor; examples of livestock include cattle, sheep, goats,
horses, pigs, donkeys, camels, buffalo, rabbits, hens, turkeys,
ducks and geese (e.g., raised for meat, milk, butter, eggs, fur,
leather, feathers and/or wool). By combating parasites, fatalities
and performance reduction (in terms of meat, milk, wool, skins,
eggs, etc.) are reduced, so that applying a composition comprising
a compound of Formula 1 allows more economic and simple husbandry
of animals.
[0217] Compounds and compositions of Formula 1 are especially
suitable for combating parasitic invertebrate pests that infest
companion animals and pets (e.g., dogs, cats, pet birds and
aquarium fish), research and experimental animals (e.g., hamsters,
guinea pigs, rats and mice), as well as animals raised for/in zoos,
wild habitats and/or circuses.
[0218] In an embodiment of this invention, the animal is preferably
a vertebrate, and more preferably a mammal, avian or fish. In a
particular embodiment, the animal subject is a mammal (including
great apes, such as humans). Other mammalian subjects include
primates (e.g., monkeys), bovine (e.g., cattle or dairy cows),
porcine (e.g., hogs or pigs), ovine (e.g., goats or sheep), equine
(e.g., horses), canine (e.g., dogs), feline (e.g., house cats),
camels, deer, donkeys, buffalos, antelopes, rabbits, and rodents
(e.g., guinea pigs, squirrels, rats, mice, gerbils, and hamsters).
Avians include Anatidae (swans, ducks and geese), Columbidae (e.g.,
doves and pigeons), Phasianidae (e.g., partridges, grouse and
turkeys), Thesienidae (e.g., domestic chickens), Psittacines (e.g.,
parakeets, macaws, and parrots), game birds, and ratites (e.g.,
ostriches).
[0219] Birds treated or protected by the compounds of Formula 1 can
be associated with either commercial or noncommercial aviculture.
These include Anatidae, such as swans, geese, and ducks,
Columbidae, such as doves and domestic pigeons, Phasianidae, such
as partridge, grouse and turkeys, Thesienidae, such as domestic
chickens, and Psittacines, such as parakeets, macaws and parrots
raised for the pet or collector market, among others.
[0220] For purposes of the present invention, the term "fish" shall
be understood to include without limitation, the Teleosti grouping
of fish, i.e., teleosts. Both the Salmoniformes order (which
includes the Salmonidae family) and the Perciformes order (which
includes the Centrarchidae family) are contained within the
Teleosti grouping. Examples of potential fish recipients include
the Salmonidae, Serranidae, Sparidae, Cichlidae, and Centrarchidae,
among others.
[0221] Other animals are also contemplated to benefit from the
inventive methods, including marsupials (such as kangaroos),
reptiles (such as farmed turtles), and other economically important
domestic animals for which the inventive methods are safe and
effective in treating or preventing parasite infection or
infestation.
[0222] Examples of parasitic invertebrate pests controlled by
administering a pesticidally effective amount of a compound of
Formula 1 to an animal to be protected include ectoparasites
(arthropods, acarines, etc.) and endoparasites (helminths, e.g.,
nematodes, trematodes, cestodes, acanthocephalans, etc.).
[0223] The disease or group of diseases described generally as
helminthiasis is due to infection of an animal host with parasitic
worms known as helminths. The term `helminths` is meant to include
nematodes, trematodes, cestodes and acanthocephalans. Helminthiasis
is a prevalent and serious economic problem with domesticated
animals such as swine, sheep, horses, cattle, goats, dogs, cats and
poultry.
[0224] Among the helminths, the group of worms described as
nematodes causes widespread and at times serious infection in
various species of animals. Nematodes that are contemplated to be
treated by the compounds of this invention and by the inventive
methods include, without limitation, the following genera:
Acanthocheilonema, Aelurostrongylus, Ancylostoma, Angiostrongylus,
Ascaridia, Ascaris, Brugia, Bunostomum, Capillaria, Chabertia,
Cooperia, Crenosoma, Dictyocaulus, Dioctophyme, Dipetalonema,
Diphyllobothrium, Dirofilaria, Dracunculus, Enterobius, Filaroides,
Haemonchus, Heterakis, Lagochilascaris, Loa, Mansonella,
Muellerius, Necator, Nematodirus, Oesophagostomum, Ostertagia,
Oxyuris, Parafilaria, Parascaris, Physaloptera, Protostrongylus,
Setaria, Spirocerca, Stephanofilaria, Strongyloides, Strongylus,
Thelazia, Toxascaris, Toxocara, Trichinella, Trichonema,
Trichostrongylus, Trichuris, Uncinaria and Wuchereria.
[0225] Of the above, the most common genera of nematodes infecting
the animals referred to above are Haemonchus, Trichostrongylus,
Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostomum,
Oesophagostomum, Chabertia, Trichuris, Strongylus, Trichonema,
Dictyocaulus, Capillaria, Heterakis, Toxocara, Ascaridia, Oxyuris,
Ancylostoma, Uncinaria, Toxascaris and Parascaris. Certain of
these, such as Nematodirus, Cooperia and Oesophagostomum attack
primarily the intestinal tract while others, such as Haemonchus and
Ostertagia, are more prevalent in the stomach while others such as
Dictyocaulus are found in the lungs. Still other parasites may be
located in other tissues such as the heart and blood vessels,
subcutaneous and lymphatic tissue and the like.
[0226] Trematodes that are contemplated to be treated by the
compounds of this invention and by the inventive methods include,
without limitation, the following genera: Alaria, Fasciola,
Nanophyetus, Opisthorchis, Paragonimus and Schistosoma.
[0227] Cestodes that are contemplated to be treated by the
compounds of this invention and by the inventive methods include,
without limitation, the following genera: Diphyllobothrium,
Diplydium, Spirometra and Taenia.
[0228] The most common genera of parasites of the gastrointestinal
tract of humans are Ancylostoma, Necator, Ascaris, Strongyloides,
Trichinella, Capillaria, Trichuris and Enterobius. Other medically
important genera of parasites which are found in the blood or other
tissues and organs outside the gastrointestinal tract are the
filarial worms such as Wuchereria, Brugia, Onchocerca and Loa, as
well as Dracunculus and extra intestinal stages of the intestinal
worms Strongyloides and Trichinella.
[0229] Numerous other helminth genera and species are known to the
art, and are also contemplated to be treated by the compounds of
Formula 1. These are enumerated in great detail in Textbook of
Veterinary Clinical Parasitology, Volume 1, Helminths, E. J. L.
Soulsby, F. A. Davis Co., Philadelphia, Pa.; Helminths, Arthropods
and Protozoa, (6.sup.th Edition of Monnig's Veterinary
Helminthology and Entomology), E. J. L. Soulsby, The Williams and
Wilkins Co., Baltimore, Md.
[0230] The compounds of Formula 1 are effective against a number of
animal ectoparasites (e.g., arthropod ectoparasites of mammals and
birds).
[0231] Insect and acarine pests include, e.g., biting insects such
as flies and mosquitoes, mites, ticks, lice, fleas, true bugs,
parasitic maggots, and the like.
[0232] Adult flies include, e.g., the horn fly or Haematobia
irritans, the horse fly or Tabanus spp., the stable fly or Stomoxys
calcitrans, the black fly or Simulium spp., the deer fly or
Chrysops spp., the louse fly or Melophagus ovinus, and the tsetse
fly or Glossina spp. Parasitic fly maggots include, e.g., the bot
fly (Oestrus ovis and Cuterebra spp.), the blow fly or Phaenicia
spp., the screwworm or Cochliomyia hominivorax, the cattle grub or
Hypoderma spp., the fleeceworm and the Gastrophilus of horses.
Mosquitoes include, for example, Culex spp., Anopheles spp. and
Aedes spp.
[0233] Mites include Mesostigmata spp. e.g., mesostigmatids such as
the chicken mite, Dermanyssus gallinae; itch or scab mites such as
Sarcoptidae spp. for example, Sarcoptes scabiei; mange mites such
as Psoroptidae spp. including Chorioptes bovis and Psoroptes ovis;
chiggers e.g., Trombiculidae spp. for example the North American
chigger, Trombicula alfreddugesi.
[0234] Ticks include, e.g., soft-bodied ticks including Argasidae
spp. for example Argas spp. and Ornithodoros spp.; hard-bodied
ticks including Ixodidae spp., for example Rhipicephalus
sanguineus, Dermacentor variabilis, Dermacentor andersoni,
Amblyomma americanum, Ixodes scapularis and other Rhipicephalus
spp. (including the former Boophilus genera).
[0235] Lice include, e.g., sucking lice, e.g., Menopon spp. and
Bovicola spp.; biting lice, e.g., Haematopinus spp., Linognathus
spp. and Solenopotes spp.
[0236] Fleas include, e.g., Ctenocephalides spp., such as dog flea
(Ctenocephalides canis) and cat flea (Ctenocephalides felis);
Xenopsylla spp. such as oriental rat flea (Xenopsylla cheopis); and
Pulex spp. such as human flea (Pulex irritans).
[0237] True bugs include, e.g., Cimicidae or e.g., the common bed
bug (Cimex lectularius); Triatominae spp. including triatomid bugs
also known as kissing bugs; for example Rhodnius prolixus and
Triatoma spp.
[0238] Generally, flies, fleas, lice, mosquitoes, gnats, mites,
ticks and helminths cause tremendous losses to the livestock and
companion animal sectors. Arthropod parasites also are a nuisance
to humans and can vector disease-causing organisms in humans and
animals.
[0239] Numerous other parasitic invertebrate pests are known to the
art, and are also contemplated to be treated by the compounds of
Formula 1. These are enumerated in great detail in Medical and
Veterinary Entomology, D. S. Kettle, John Wiley & Sons, New
York and Toronto; Control of Arthropod Pests of Livestock: A Review
of Technology, R. O. Drummand, J. E. George, and S. E. Kunz, CRC
Press, Boca Raton, Fla.
[0240] In particular, the compounds of Formula 1 are especially
effective against ectoparasites including Stomoxys calcitrans
(stable fly); ticks such as Ixodes spp., Boophilus spp.,
Rhipicephalus spp., Amblyomma spp., Dermacentor spp., Hyalomma spp.
and Haemaphysalis spp.; and fleas such as Ctenocephalides felis
(cat flea) and Ctenocephalides canis (dog flea).
[0241] The compounds of Formula 1 may also be effective against
ectoparasites including: flies such as Haematobia (Lyperosia)
irritans (horn fly), Simulium spp. (blackfly), Glossina spp.
(tsetse flies), Hydrotaea irritans (head fly), Musca autumnalis
(face fly), Musca domestica (house fly), Morellia simplex (sweat
fly), Tabanus spp. (horse fly), Hypoderma bovis, Hypoderma
lineatum, Lucilia sericata, Lucilia cuprina (green blowfly),
Calliphora spp. (blowfly), Protophormia spp., Oestrus ovis (nasal
botfly), Culicoides spp. (midges), Hippobosca equine, Gastrophilus
intestinalis, Gastrophilus haemorrhoidalis and Gastrophilus
nasalis; lice such as Bovicola (Damalinia) bovis, Bovicola equi,
Haematopinus asini, Felicola subrostratus, Heterodoxus spiniger,
Lignonathus setosus and Trichodectes canis; keds such as Melophagus
ovinus; and mites such as Psoroptes spp., Sarcoptes scabei,
Chorioptes bovis, Demodex equi, Cheyletiella spp., Notoedres cati,
Trombicula spp. and Otodectes cyanotis (ear mites).
[0242] Other biologically active compounds or agents may be
administered at the same or different times as the compounds of
Formula 1. Such compounds, for example, may be useful adjuncts in
Formula 1 compositions for the present method. As noted below, such
biologically active compounds may be included in the composition of
Formula 1. Such biologically active compounds for use in the
present invention include the organophosphate pesticides. This
class of pesticides has very broad activity as insecticides and, in
certain instances, anthelminitic activity. Organophosphate
pesticides include, e.g., dicrotophos, terbufos, dimethoate,
diazinon, disulfoton, trichlorfon, azinphos-methyl, chlorpyrifos,
malathion, oxydemeton-methyl, methamidophos, acephate, ethyl
parathion, methyl parathion, mevinphos, phorate, carbofenthion and
phosalone. Compositions of Formula 1 compounds for the present
method are also comtemplated to include carbamate-type pesticides,
including, e.g., carbaryl, carbofuran, aldicarb, molinate,
methomyl, carbofuran, etc., as well as combinations with the
organochlorine type pesticides. Compositions of Formula 1 compounds
are further contemplated to include combinations with biological
pesticides, including repellents, the pyrethrins (as well as
synthetic variations thereof, e.g., allethrin, resmethrin,
permethrin, tralomethrin), and nicotine, that is often employed as
an acaricide. Other contemplated combinations are with
miscellaneous pesticides including: Bacillus thuringiensis,
chlorobenzilate, formamidines (e.g., amitraz), copper compounds
(e.g., copper hydroxide and cupric oxychloride sulfate),
cyfluthrin, cypermethrin, dicofol, endosulfan, esfenvalerate,
fenvalerate, lambda-cyhalothrin, methoxychlor and sulfur.
[0243] Of note are additional biologically active compounds or
agents selected from art-known anthelmintics, such as, for example,
avermectins (e.g., ivermectin, moxidectin, milbemycin),
benzimidazoles (e.g., albendazole, triclabendazole),
salicylanilides (e.g., closantel, oxyclozanide), substituted
phenols (e.g., nitroxynil), pyrimidines (e.g., pyrantel),
imidazothiazoles (e.g., levamisole) and praziquantel.
[0244] Other biologically active compounds or agents useful in the
Formula 1 compositions for the present method can be selected from
Insect Growth Regulators (IGRs) and Juvenile Hormone Analogues
(JHAs) such as diflubenzuron, triflumuron, fluazuron, cyromazine,
methoprene, etc., thereby providing both initial and sustained
control of parasites (at all stages of insect development,
including eggs) on the animal subject, as well as within the
environment of the animal subject.
[0245] Of note are biologically active compounds or agents useful
in the Formula 1 compositions for the present method selected from
the avermectin class of antiparasitic compounds. As stated above,
the avermectin family of compounds includes very potent
antiparasitic agents known to be useful against a broad spectrum of
endoparasites and ectoparasites in mammals.
[0246] A preferred compound for use within the scope of the present
invention is ivermectin. Ivermectin is a semi-synthetic derivative
of avermectin and is generally produced as a mixture of at least
80% 22,23-dihydroavermectin B.sub.1a and less than 20%
22,23-dihydroavermectin B.sub.1b. Ivermectin is disclosed in U.S.
Pat. No. 4,199,569.
[0247] Abamectin is an avermectin that is disclosed as avermectin
B.sub.1a/B.sub.1b in U.S. Pat. No. 4,310,519. Abamectin contains at
least 80% of avermectin B.sub.1a and not more than 20% of
avermectin B.sub.1b.
[0248] Another preferred avermectin is doramectin, also known as
25-cyclohexyl-avermectin B.sub.1. The structure and preparation of
doramectin is disclosed in U.S. Pat. No. 5,089,480.
[0249] Another preferred avermectin is moxidectin. Moxidectin, also
known as LL-F28249 alpha, is known from U.S. Pat. No.
4,916,154.
[0250] Another preferred avermectin is selamectin. Selamectin is
25-cyclohexyl-25-de(1-methylpropyl)-5-deoxy-22,23-dihydro-5-(hydroxyimino-
)-avermectin B.sub.1 monosaccharide.
[0251] Milbemycin, or B41, is a substance which is isolated from
the fermentation broth of a milbemycin-producing strain of
Streptomyces. The microorganism, the fermentation conditions and
the isolation procedures are described in U.S. Pat. Nos. 3,950,360
and 3,984,564.
[0252] Emamectin (4''-deoxy-4''-epi-methylaminoavermectin B.sub.1),
which can be prepared as described in U.S. Pat. Nos. 5,288,710 and
5,399,717, is a mixture of two homologues,
4''-deoxy-4''-epi-methylaminoavermectin B.sub.1a and
4''-deoxy-4''-epi-methylaminoavermectin B.sub.1b. Preferably, a
salt of emamectin is used. Non-limiting examples of salts of
emamectin which may be used in the present invention include the
salts described in U.S. Pat. No. 5,288,710, e.g., salts derived
from benzoic acid, substituted benzoic acid, benzenesulfonic acid,
citric acid, phosphoric acid, tartaric acid, maleic acid, and the
like. Most preferably, the emamectin salt used in the present
invention is emamectin benzoate.
[0253] Eprinomectin is chemically known as
4''-epi-acetylamino-4''-deoxy-avermectin Eprinomectin was
specifically developed to be used in all cattle classes and age
groups. It was the first avermectin to show broad-spectrum activity
against both endo- and ectoparasites while also leaving minimal
residues in meat and milk. It has the additional advantage of being
highly potent when delivered topically.
[0254] The Formula 1 compositions for the present method optionally
comprise combinations of one or more of the following antiparasite
compounds: imidazo[1,2-b]pyridazine compounds as described by U.S.
Patent Application Publication No. 2005/0182059 A1; 1-(4-mono and
di-halomethylsulphonylphenyl)-2-acylamino-3-fluoropropanol
compounds, as described by U.S. Pat. No. 7,361,689;
trifluoromethanesulfonanilide oxime ether derivatives, as described
by U.S. Pat. No. 7,312,248; and
n-[(phenyloxy)phenyl]-1,1,1-trifluoromethanesulfonamide and
n-[(phenylsulfanyl)phenyl]-1,1,1-trifluoromethanesulfonamide
derivatives, as described by PCT Patent Application Publication WO
2006/135648.
[0255] The Formula 1 compositions may also further comprise a
flukicide. Suitable flukicides include, for example,
triclabendazole, fenbendazole, albendazole, clorsulon and
oxibendazole. It will be appreciated that the above combinations
may further include combinations of antibiotic, antiparasitic and
anti-fluke active compounds.
[0256] In addition to the above combinations, it is also
contemplated to provide Formula 1 compositions, as described herein
for the present method, with other animal health remedies such as
trace elements, anti-inflammatories, anti-infectives, hormones,
dermatological preparations, including antiseptics and
disinfectants, and immunobiologicals such as vaccines and antisera
for the prevention of disease.
[0257] For example, such antinfectives include one or more
antibiotics that are optionally co-administered during treatment
using the inventive methods, e.g., in a combined composition and/or
in separate dosage forms. Art-known antibiotics suitable for this
purpose include, for example, those listed herein below.
[0258] One useful antibiotic is florfenicol, also known as
D-(threo)-1-(4-methylsulfonylphenyl)chloroacetamido-3-fluoro-1-propanol.
Another preferred antibiotic compound is
D-(threo)-1-(4-methylsulfonylphenyl)-2-difluoroacetamido-3-fluoro-1-propa-
nol. Another useful antibiotic is thiamphenicol. Processes for the
manufacture of these antibiotic compounds, and intermediates useful
in such processes, are described in U.S. Pat. No. 431,857;
4,582,918; 4,973,750; 4,876,352; 5,227,494; 4,743,700; 5,567,844;
5,105,009; 5,382,673; 5,352,832; and 5,663,361. Other florfenicol
analogs and/or prodrugs have been disclosed and such analogs also
can be used in the compositions and methods of the present
invention (see e.g., U.S. Pat. Nos. 7,041,670 and 7,153,842).
[0259] Another useful antibiotic compound is tilmicosin. Tilmicosin
is a macrolide antibiotic that is chemically defined as
20-dihydro-20-deoxy-20-(cis-3,5-dimethylpiperidin-1-yl)-desmycosin
and is disclosed in U.S. Pat. No. 4,820,695.
[0260] Another useful antibiotic for use in the present invention
is tulathromycin. Tulathromycin may be prepared in accordance with
the procedures set forth in U.S. Pat. No. 6,825,327.
[0261] Further antibiotics for use in the present invention include
the cephalosporins such as, for example, ceftiofur, cefquinome,
etc. The concentration of the cephalosporin in the formulation of
the present invention optionally varies between about 1 mg/mL to
500 mg/mL.
[0262] Another useful antibiotic includes the fluoroquinolones,
such as, for example, enrofloxacin, danofloxacin, difloxacin,
orbifloxacin and marbofloxacin. In the case of enrofloxacin, it may
be administered in a concentration of about 100 mg/mL. Danofloxacin
may be present in a concentration of about 180 mg/mL.
[0263] Other useful macrolide antibiotics include compounds from
the class of ketolides, or, more specifically, the azalides. Such
compounds are described in, for example, U.S. Pat. Nos. 6,514,945;
6,472,371; 6,270,768; 6,437,151; 6,271,255; 6,239,12; 5,958,888;
6,339,063; and 6,054,434.
[0264] Other useful antibiotics include the tetracyclines,
particularly chlortetracycline and oxytetracycline. Other
antibiotics may include .beta.-lactams such as penicillins, e.g.,
penicillin, ampicillin, amoxicillin, or a combination of
amoxicillin with clavulanic acid or other beta lactamase
inhibitors.
[0265] Treatments of the invention are by conventional means such
as by enteral administration in the form of, for example, tablets,
capsules, drinks, drenching preparations, granulates, pastes, boli,
feed-through procedures, or suppositories; or by parenteral
administration, such as, for example, by injection (including
intramuscular, subcutaneous, intravenous, intraperitoneal) or
implants; or by nasal administration.
[0266] The compounds of Formula 1 may be administered in a
controlled release form, for example in subcutaneous or orally
adminstered slow release formulations.
[0267] Typically a parasiticidal composition according to the
present invention comprises a mixture of a compound of Formula 1,
an N-oxide or a salt thereof, with one or more pharmaceutically or
veterinarily acceptable carriers comprising excipients and
auxiliaries selected with regard to the intended route of
administration (e.g., oral or parenteral administration such as
injection) and in accordance with standard practice. In addition, a
suitable carrier is selected on the basis of compatibility with the
one or more active ingredients in the composition, including such
considerations as stability relative to pH and moisture content.
Therefore of note is a composition for protecting an animal from an
invertebrate parasitic pest comprising a parasitically effective
amount of a compound of Formula 1 and at least one carrier.
[0268] For parenteral administration including intravenous,
intramuscular and subcutaneous injection, a compound of Formula 1
can be formulated in suspension, solution or emulsion in oily or
aqueous vehicles, and may contain adjuncts such as suspending,
stabilizing and/or dispersing agents. The compounds of Formula 1
may also be formulated for bolus injection or continuous infusion.
Pharmaceutical compositions for injection include aqueous solutions
of water-soluble forms of active ingredients (e.g., a salt of an
active compound), preferably in physiologically compatible buffers
containing other excipients or auxiliaries as are known in the art
of pharmaceutical formulation. Additionally, suspensions of the
active compounds may be prepared in a lipophilic vehicle. Suitable
lipophilic vehicles include fatty oils such as sesame oil,
synthetic fatty acid esters such as ethyl oleate and triglycerides,
or materials such as liposomes. Aqueous injection suspensions may
contain substances that increase the viscosity of the suspension,
such as sodium carboxymethyl cellulose, sorbitol, or dextran.
Formulations for injection may be presented in unit dosage form,
e.g., in ampoules or in multi-dose containers. Alternatively, the
active ingredient may be in powder form for constitution with a
suitable vehicle, e.g., sterile, pyrogen-free water, before
use.
[0269] In addition to the formulations described supra, the
compounds of Formula 1 may also be formulated as a depot
preparation. Such long acting formulations may be administered by
implantation (for example, subcutaneously or intramuscularly) or by
intramuscular or subcutaneous injection. The compounds of Formula 1
may be formulated for this route of administration with suitable
polymeric or hydrophobic materials (for instance, in an emulsion
with a pharmacologically acceptable oil), with ion exchange resins,
or as a sparingly soluble derivative such as, without limitation, a
sparingly soluble salt.
[0270] For administration by inhalation, the compounds of Formula 1
can be delivered in the form of an aerosol spray using a
pressurized pack or a nebulizer and a suitable propellant, e.g.,
without limitation, dichlorodifluoromethane,
trichlorofluoromethane, dichlorotetrafluoroethane or carbon
dioxide. In the case of a pressurized aerosol, the dosage unit may
be controlled by providing a valve to deliver a metered amount.
Capsules and cartridges of, for example, gelatin for use in an
inhaler or insufflator may be formulated containing a powder mix of
the compound and a suitable powder base such as lactose or
starch.
[0271] Compounds of Formula 1 have been discovered to have
surprisingly favorable pharmacokinetic and pharmacodynamic
properties providing systemic availability from oral administration
and ingestion. Therefore after ingestion by the animal to be
protected, parasiticidally effective concentrations of compounds of
Formula 1 in the bloodstream protect the treated animal from
blood-sucking pests such as fleas, ticks and lice. Therefore of
note is a composition for protecting an animal from an invertebrate
parasite pest in a form for oral administration (i.e. comprising,
in addition to a parasiticidally effective amount of a compound of
Formula 1, one or more carriers selected from binders and fillers
suitable for oral administration and feed concentrate
carriers).
[0272] For oral administration in the form of solutions (the most
readily available form for absorption), emulsions, suspensions,
pastes, gels, capsules, tablets, boluses, powders, granules,
rumen-retention and feed/water/lick blocks, a compound of Formula 1
can be formulated with binders/fillers known in the art to be
suitable for oral administration compositions, such as sugars and
sugar derivatives (e.g., lactose, sucrose, mannitol, sorbitol),
starch (e.g., maize starch, wheat starch, rice starch, potato
starch), cellulose and derivatives (e.g., methylcellulose,
carboxymethylcellulose, ethylhydroxycellulose), protein derivatives
(e.g., zein, gelatin), and synthetic polymers (e.g., polyvinyl
alcohol, polyvinylpyrrolidone). If desired, lubricants (e.g.,
magnesium stearate), disintegrating agents (e.g., cross-linked
polyvinylpyrrolidinone, agar, alginic acid) and dyes or pigments
can be added. Pastes and gels often also contain adhesives (e.g.,
acacia, alginic acid, bentonite, cellulose, xanthan gum, colloidal
magnesium aluminum silicate) to aid in keeping the composition in
contact with the oral cavity and not being easily ejected.
[0273] A preferred embodiment is a composition of the present
method formulated into a chewable and/or edible product (e.g., a
chewable treat or edible tablet). Such a product would ideally have
a taste, texture and/or aroma favored by the animal to be protected
so as to facilitate oral administration of the compound of Formula
1.
[0274] If the parasiticidal compositions are in the form of feed
concentrates, the carrier is typically selected from
high-performance feed, feed cereals or protein concentrates. Such
feed concentrate-containing compositions can, in addition to the
parasiticidal active ingredients, comprise additives promoting
animal health or growth, improving quality of meat from animals for
slaughter or otherwise useful to animal husbandry. These additives
can include, for example, vitamins, antibiotics, chemotherapeutics,
bacteriostats, fungistats, coccidiostats and hormones.
[0275] The compounds of Formula 1 may also be formulated in rectal
compositions such as suppositories or retention enemas, using,
e.g., conventional suppository bases such as cocoa butter or other
glycerides.
[0276] The formulations for the method of this invention may
include an antioxidant, such as BHT (butylated hydroxytoluene). The
antioxidant is generally present in amounts of at 0.1-5% (wt/vol).
Some of the formulations require a solubilizer, such as oleic acid,
to dissolve the active agent, particularly if spinosad is included.
Common spreading agents used in these pour-on formulations include
isopropyl myristate, isopropyl palmitate, caprylic/capric acid
esters of saturated C.sub.12-C.sub.18 fatty alcohols, oleic acid,
oleyl ester, ethyl oleate, triglycerides, silicone oils and
dipropylene glycol methyl ether. The pour-on formulations for the
method of this invention are prepared according to known
techniques. Where the pour-on is a solution, the
parasiticide/insecticide is mixed with the carrier or vehicle,
using heat and stirring if required. Auxiliary or additional
ingredients can be added to the mixture of active agent and
carrier, or they can be mixed with the active agent prior to the
addition of the carrier. Pour-on formulations in the form of
emulsions or suspensions are similarly prepared using known
techniques.
[0277] Other delivery systems for relatively hydrophobic
pharmaceutical compounds may be employed. Liposomes and emulsions
are well-known examples of delivery vehicles or carriers for
hydrophobic drugs. In addition, organic solvents such as
dimethylsulfoxide may be used, if needed.
[0278] The rate of application required for effective parasitic
invertebrate pest control (i.e. "pesticidally effective amount")
will depend on such factors as the species of parasitic
invertebrate pest to be controlled, the pest's life cycle, life
stage, its size, location, time of year, host crop or animal,
feeding behavior, mating behavior, ambient moisture, temperature,
and the like. One skilled in the art can easily determine the
pesticidally effective amount necessary for the desired level of
parasitic invertebrate pest control.
[0279] In general for veterinary use, a compound or composition of
Formula 1 is administered in a pesticidally effective amount to an
animal, particularly a homeothermic animal, to be protected from
parasitic invertebrate pests. A pesticidally effective amount is
the amount of active ingredient needed to achieve an observable
effect diminishing the occurrence or activity of the target
parasitic invertebrate pest. One skilled in the art will appreciate
that the pesticidally effective dose can vary for the various
compounds and compositions useful for the method of the present
invention, the desired pesticidal effect and duration, the target
parasitic invertebrate pest species, the animal to be protected,
the mode of application and the like, and the amount needed to
achieve a particular result can be determined through simple
experimentation.
[0280] For oral or parenteral administration to animals, a dose of
a compound of the present invention administered at suitable
intervals typically ranges from about 0.01 mg/kg to about 100
mg/kg, and preferably from about 0.01 mg/kg to about 30 mg/kg of
animal body weight.
[0281] Suitable intervals for the administration of compounds of
the present invention to animals range from about daily to about
yearly. Of note are administration intervals ranging from about
weekly to about once every 6 months. Of particular note are monthly
adminstration intervals (i.e. administering the compound to the
animal once every month).
[0282] The following Tests demonstrate the control efficacy of
compounds of Formula 1 on specific pests. "Control efficacy"
represents inhibition of parasitic invertebrate pest development
(including mortality) that causes significantly reduced feeding.
The pest control protection afforded by the compounds is not
limited, however, to these species. See Index Tables A and B for
compound descriptions.
TABLE-US-00007 INDEX TABLE A ##STR00013## mp Cmpd R.sup.1 R.sup.2
R.sup.3 R.sup.4 R.sup.6 (.degree. C.) 1 Cl H Cl CH.sub.3
CH.sub.2(2-pyridinyl) 67-69 2 Cl H Cl CH.sub.3
CH.sub.2CH.sub.2SCH.sub.3 * 3 Cl H Cl CH.sub.3
CH.sub.2C(O)NHCH.sub.2CF.sub.3 * 4 Cl H Cl CH.sub.3
CH(CH.sub.3)CH.sub.2CH.sub.2SCH.sub.3 * 5 Cl H Cl CH.sub.3
CH.sub.2CH.sub.2S(O)CH.sub.3 * 6 Cl H Cl CH.sub.3
CH.sub.2CH.sub.2S(O).sub.2CH.sub.3 * 7 Cl H Cl F
CH.sub.2(2-pyridinyl) * 8 Cl H Cl CH.sub.3
C(CH.sub.3).sub.2CH.sub.2SCH.sub.3 * 9 Cl H Cl CH.sub.3
(R)--CH(CH.sub.3)C(O)NHCH.sub.2CF.sub.3 * 10 Cl H Cl CH.sub.3
C(CH.sub.3).sub.2CH.sub.2S(O).sub.2CH.sub.3 * * See Index Table B
for .sup.1H NMR data.
TABLE-US-00008 INDEX TABLE B Compound .sup.1H NMR Data (CDCl.sub.3
solution unless indicated otherwise).sup.a 2 .delta. 7.52 (m, 4H),
7.43 (m, 2H), 6.20 (br s, 1H), 4.08 (d, 1H), 3.72 (d, 1H), 3.66 (m,
2H), 2.76 (t, 2H), 2.49 (s, 3H), 2.15 (s, 3H). 3 .delta. 7.43-7.54
(m, 6H), 6.99 (br t, 1H), 6.75 (br t, 1H), 4.21 (d, 2H), 4.08 (d,
1H), 3.95 (m, 2H), 3.70 (d, 1H), 2.47 (s, 3H). 4 .delta. 7.51 (m,
4H), 7.43 (m, 2H), 5.74 (br d, 1H), 4.08 (d, 1H), 3.70 (d, 1H),
2.60 (t, 2H), 2.47 (s, 3H), 2.13 (s, 3H), 1.3 (d, 3H). 5 .delta.
7.5 (m, 4H), 7.43 (m, 1H), 7.0 (s, 1H), 6.84 (br s, 1H), 4.08 (d,
1H), 4.0 (m, 2H), 3.71 (d, 1H), 3.17 (m, 1H), 2.91 (m, 1H), 2.68
(s, 3H), 2.49 (s, 3H). 6 .delta. 7.5 (m, 4H), 7.43 (m, 2H), 7.0 (s,
1H), 6.58 (br s, 1H), 4.08 (d, 1H), 4.0 (m, 2H), 3.71 (d, 1H), 3.36
(m, 2H), 3.0 (s, 3H), 2.49 (s, 3H). 7 .delta. 8.6 (d, 1H), 8.2 (t,
1H), 8.1 (m, 1H), 7.7 (dt, 1H), 7.6-7.4 (m, 5H), 7.35 (d, 1H), 7.25
(m, 1H), 4.8 (d, 2H), 4.1 (d, 1H), 3.7 (d, 1H). 8 .delta. 7.5 (m,
4H), 7.43 (m, 2H), 5.75 (br s, 1H), 4.08 (d, 1H), 3.71 (d, 1H),
3.07 (s, 2H), 2.48 (s, 3H), 2.18 (s, 3H), 1.51 (s, 6H). 9 .delta.
7.36-7.51 (m, 7H), 6.85 (dd, 1H), 4.83 (m, 1H), 4.09 (d, 1H), 3.88
(m, 2H), 3.71 (d, 1H), 2.40 (s, 3H), 1.51 (d, 3H). 10 .delta. 7.5
(m, 5H), 7.43 (s, 1H), 6.03 (br s, 1H), 4.08 (d, 1H), 3.79 (s, 2H),
3.71 (d, 1H), 2.95 (s, 3H), 2.47 (s, 3H), 1.69 (s, 6H). .sup.a1H
NMR data are in ppm downfield from tetramethylsilane. Couplings are
designated by (s)-singlet, (d)-doublet, (t)-triplet, (q)-quartet,
(dd)-doublet of doublets, (dt)-doublet of triplets, (br)-broad
peaks, (m)-multiplet.
[0283] Methods for preparing the compounds listed in Index Table A
are disclosed in PCT Patent Publication WO 2005/085216. To the
extent necessary to teach the methods of preparing the compounds
Formula 1, (and only to the extent that they are not inconsistent
with the disclosure herein) this patent publication is herein
incorporated by reference.
Biological Examples of the Invention
Test A
[0284] For evaluating control of the cat flea (Ctenocephalides
felis), a CD-1.RTM. mouse (about 30 g, male, obtained from Charles
River Laboratories, Wilmington, Mass.) was orally dosed with a test
compound in an amount of 10 mg/kg solubilized in propylene
glycol/glycerol formal (60:40). Two hours after oral administration
of the test compound, approximately 8 to 16 adult fleas were
applied to each mouse. The fleas were then evaluated for mortality
48 hours after flea application to the mouse.
[0285] Of the compounds tested, the following compounds resulted in
at least 50% mortality: 1, 2, 3 and 4.
Test B
[0286] For evaluating control of the cat flea (Ctenocephalides
felis), a CD-1.RTM. mouse (about 30 g, male, obtained from Charles
River Laboratories, Wilmington, Mass.) was orally dosed with a test
compound in an amount of 10 mg/kg solubilized in propylene
glycol/glycerol formal (60:40). Twenty four hours after oral
administration of the test compound, approximately 8 to 16 adult
fleas were applied to each mouse. The fleas were then evaluated for
mortality 48 hours after flea application to the mouse.
[0287] Of the compounds tested, the following compounds resulted in
at least 20% mortality: 1, 2 and 3. The following compounds
resulted in at least 50% mortality: 2 and 3.
Test C
[0288] For evaluating control of the cat flea (Ctenocephalides
felis), a CD-1.RTM. mouse (about 30 g, male, obtained from Charles
River Laboratories, Wilmington, Mass.) was subcutaneously dosed
with a test compound in an amount of 10 mg/kg solubilized in
propylene glycol/glycerol formal (60:40). Two hours after oral
administration of the test compound, approximately 8 to 16 adult
fleas were applied to each mouse. The fleas were then evaluated for
mortality 48 hours after flea application to the mouse.
[0289] Of the compounds tested, the following compounds resulted in
at least 20% mortality: 1, 2 and 3. The following compounds
resulted in at least 50% mortality: 1 and 3.
Test D
[0290] For evaluating control of the cat flea (Ctenocephalides
felis), a test compound was solubilized in propylene
glycol/glycerol formal (60:40) and then diluted in bovine blood to
a final test rate of 30 ppm. The treated blood was placed in a
tube, and the bottom of the tube was covered with a membrane.
Approximately 10 adult cat fleas were allowed to feed through the
membrane on the treated blood. The adult fleas were then evaluated
for mortality 72 hours later.
[0291] Of the compounds tested, the following compounds resulted in
at least 50% mortality: 1, 2, 3, 5, 6, 7, 8, 9 and 10.
* * * * *