US2014256743A1PendingUtilityA1
Cathepsin cysteine protease inhibitors
Est. expiryMar 5, 2022(expired)· nominal 20-yr term from priority
Inventors:Christopher BaylyCameron BlackSerge LegerChun Sing LiDan MckayChristophe MellonJacques Yves GauthierVouy Linh TruongCheuk K. LauMichel TherienMichael J. GreenBernard L. HirschbeinJames William JancJames T. PalmerChitra Baskaran
A61P 43/00A61P 35/04A61P 3/14A61P 35/00A61P 29/00A61P 19/06A61P 19/08A61P 19/02A61P 19/10A61P 19/04A61P 19/00C07D 233/64C07D 231/12C07D 271/06C07C 255/46C07D 261/08C07C 255/29A61K 31/426C07D 307/52C07C 317/32C07D 239/26C07D 277/30C07D 333/20A61K 31/4418C07C 259/10C07D 277/28C07D 215/12C07C 255/58C07D 295/155C07C 2601/02C07D 401/04C07C 311/37C07D 213/57C07D 213/70C07D 241/12C07C 255/25C07D 213/38C07D 213/64C07D 213/89A61K 31/18C07D 295/135A61K 31/495C07C 237/20A61K 31/4174A61K 31/165A61K 31/44C07C 2601/14C07D 417/04C07D 209/08C07D 263/32C07C 255/17A61P 1/02
62
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.
Claims
exact text as granted — not AI-modified1 . The present invention relates to compounds of the following chemical formula:
wherein R 1 is hydrogen, C 1-6 alkyl or C 2-6 alkenyl wherein said alkyl and alkenyl groups are optionally substituted with one to six halo, C 3-6 cycloalkyl, —SR 9 , —SR 12 , —SOR 9 , —SOR 12 , —SO 2 R 9 , —SO 2 R 12 , —SO 2 CH(R 12 )(R 11 ), —OR 12 , —OR 9 , —N(R 12 ) 2 , aryl, heteroaryl or heterocyclyl wherein said aryl, heteroaryl and heterocyclyl groups are optionally substituted with one or two substitutents independently selected from C 1-6 alkyl, halo, hydroxyalkyl, hydroxy, alkoxy or keto;
R 2 is hydrogen, C 1-6 alkyl or C 2-6 alkenyl wherein said alkyl and alkenyl groups are optionally substituted with one to six halo, C 3-6 cycloalkyl, —SR 9 , —SR 12 , —SOR 9 , —SOR 12 , —SO 2 R 9 , —SO 2 R 12 , —SO 2 CH(R 12 )(R 11 ), —OR 12 , —OR 9 , —N(R 12 ) 2 , aryl, heteroaryl or heterocyclyl wherein said aryl, heteroaryl and heterocyclyl groups are optionally substituted with one or two substitutents independently selected from C 1-6 alkyl, halo, hydroxyalkyl, hydroxy, alkoxy or keto;
or R 1 and R 2 can be taken together with the carbon atom to which they are attached to form a C 3-8 cycloalkyl or heterocyclyl ring wherein said ring system is optionally substituted with one or two substituents independently selected from C 1-6 alkyl, hydroxyalkyl, haloalkyl, or halo;
R 3 is hydrogen, C 1-6 alkyl or C 2-6 alkenyl wherein said alkyl and alkenyl groups are optionally substituted with C 3-6 cycloalkyl or one to six halo;
R 4 is hydrogen, C 1-6 alkyl or C 2-6 alkenyl wherein said alkyl and alkenyl groups are optionally substituted with C 3-6 cycloalkyl or one to six halo;
or R 3 and R 4 can be taken together with the carbon atom to which they are attached to form a C 3-8 cycloalkyl ring, C 5-8 cycloalkenyl ring, or five to seven membered heterocyclyl wherein said cycloalkyl, cycloalkenyl and heterocyclyl groups are optionally substituted with one or two substitutents independently selected from C 1-6 alkyl, halo, hydroxyalkyl, hydroxy, alkoxy or keto;
R 5 is selected from hydrogen or C 1-6 alkyl substituted with 1-6 halo;
R 6 is aryl, heteroaryl, C 1-6 haloalkyl, arylalkyl or heteroarylalkyl, wherein said aryl, heteroaryl, arylalkyl and heteroarylalkyl groups are optionally substituted with one, two, or three substituents independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, haloalkoxy, —SR 9 , —SR 12 , —SOR 9 , —SOR 12 , —SO 2 R 9 , —SO 2 R 12 , —SO 2 CH(R 12 )(R 11 ), —OR 12 , —N(R 10 )(R 11 ), cyano, or aryl which is optionally substituted with —SO 2 R 12 ;
each D is independently C 1-3 alkyl, C 2-3 alkenyl, C 2-3 alkynyl, aryl, heteroaryl, C 3-8 cycloalkyl or heterocyclyl wherein each said aryl, heteroaryl, cycloalkyl and heterocyclyl groups, which may be monocyclic or bicyclic, is optionally substituted on either the carbon or the heteroatom with one to five substituents independently selected from C 1-6 alkyl, haloalkyl, halo, keto, alkoxy, —SR 9 , —SR 12 , —OR 9 , —OR 12 , N(R 12 ) 2 , —SO 2 R 9 , or —SO 2 R 10 ;
R 7 is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkyloxy, halo, nitro, cyano, aryl, heteroaryl, C 3-8 cycloalkyl, heterocyclyl, —C(O)OR 10 , —C(O)OSi[CH(CH 3 ) 2 ] 3 , —OR 9 , —ORM, —C(O)R 10 , —R 10 C(O)R 9 , —C(O)R 9 , —C(O)N(R a )(R b ), —C(O)N(R 12 )(R 12 ), —C(O)N(R 10 )(R 11 ), —C(R 10 )(R 11 )OH, —SR 12 , —SR 9 , —R 10 SR 9 , —R 9 , —C(R 9 ) 3 , —C(R 10 )(R 11 )N(R 9 ) 2 , —NR 10 C(O)NR 10 S(O) 2 R 9 , —SO 2 R 12 , —SO(R 12 ), —SO 2 R 9 , —SO m N(R c )(R d ), —SO m CH(R 10 )(R 11 ), —SO 2 N(R 10 )C(O)(R 12 ), —SO 2 (R 10 )C(O)N(R 12 ) 2 , —OSO 2 R 10 , —N(R 10 )(R 11 ), —N(R 10 )C(O)N(R 10 )(R 9 ), N(R 10 )CO(R 9 ), —N(R 10 )C(O)R 10 , —N(R 10 )C(O)OR 10 , —N(R 10 )SO 2 (R 10 ), —C(R 10 )(R 11 )NR 10 C(R 10 )(R 11 )R 9 , —C(R 10 )(R 11 )N(R 10 )R 9 , —C(R 10 )(R 11 )N(R 10 )(R 11 ), —C(R 10 )(R 11 )SC(R 10 )(R 11 )(R 9 ), R 10 S—, —C(R a )(R b )NR a C(R a )(R b )(R 9 ), —C(R a )(R b )N(R a )(R b ), —C(R a )(R b )C(R a )(R b )N(R a )(R b ), —C(O)C(R a )(R b )N(R a )(R b ), —C(R a )(R b )N(R a )C(O)R 9 , —C(O)C(R a )(R b )S(R a ), C(R a )(R b )C(O)N(R a )(R b ), —B(OH) 2 , —OCH 2 O— or 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl;
wherein said groups are optionally substituted on either the carbon or the heteroatom with one to five substituents independently selected from C 1-6 alkyl, halo, keto, cyano, haloalkyl, hydroxyalkyl, —OR 9 , —NO 2 , —NH 2 , —NHS(O) 2 R 8 , —R 9 SO 2 R 12 , —SO 2 R 12 , —SO(R 12 ), —SR 12 , —SR 9 , —SO m N(R c )(R d ), —SO m N(R 10 )C(O)(R 12 ), —C(R 10 )(R 11 )N(R 10 )(R 11 ), —C(R 10 )(R 11 )OH, —COOH, —C(R a )(R b )C(O)N(R a )(R b ), —C(O)(R a )(R b ), —N(R 10 )C(R 10 )(R 11 )(R 9 ), —N(R 10 )CO(R 9 ), —NH(CH 2 ) 2 OH, —NHC(O)OR 10 , —Si(CH 3 ) 3 , heterocycyl, aryl or heteroaryl;
R 8 is hydrogen or C 1-6 alkyl;
or R 4 and R 8 or can be taken together with any of the atoms to which they may be attached or are between them to form a 4-10 membered heterocyclyl ring system wherein said ring system, which may be monocyclic or bicyclic, is optionally substituted with one or two substituents independently selected from C 1-6 alkyl, halo, hydroxyalkyl, hydroxy, keto, —OR 10 , —SR 10 or —N(R 10 ) 2 ;
R 9 is selected from the group consisting of hydrogen, aryl, aryl(C 1-4 )alkyl, heteroaryl, heteroaryl(C 1-4 )alkyl, C 3-8 cycloalkyl, C 3-8 cycloalkyl(C 1-4 )alkyl, and heterocyclyl(C 1-4 )alkyl wherein said groups can be optionally substituted with one, two, or three substituents independently selected from halo, alkoxy or —SO 2 R 12 ;
R 10 is hydrogen or C 1-6 alkyl
R 11 is hydrogen or C 1-6 alkyl;
R 12 is hydrogen or C 1-6 alkyl which is optionally substituted with one, two, or three substituents independently selected from halo, alkoxy, cyano, —NR 10 or —SR 10 ;
R a is hydrogen, C 1-6 alkyl, (C 1-6 alkyl)aryl, (C 1-6 alkyl)hydroxyl, —O(C 1-6 alkyl), hydroxyl, halo, aryl, heteroaryl, C 3-8 cycloalkyl, heterocyclyl, wherein said alkyl, aryl, heteroaryl, C 3-8 cycloalkyl and heterocyclyl can be optionally substituted on either the carbon or the heteroatom with one, two, or three substituents independently selected from C 1-6 alkyl or halo;
R b is hydrogen, C 1-6 alkyl, (C 1-6 alkyl)aryl, (C 1-6 alkyl)hydroxyl, alkoxyl, hydroxyl, halo, aryl, heteroaryl, C 3-8 cycloalkyl, heterocyclyl, wherein said alkyl, aryl, heteroaryl, C 3-8 cycloalkyl and heterocyclyl can be optionally substituted on either the carbon or the heteroatom with one, two, or three substituents independently selected from C 1-6 alkyl or halo;
or R a and R b can be taken together with the carbon atom to which they are attached or are between them to form a C 3-8 cycloalkyl ring or C 3-8 heterocyclyl ring wherein said 3-8 membered ring system may be optionally substituted with one or two substituents independently selected from C 1-6 alkyl and halo;
R c is hydrogen or C 1-6 alkyl which is optionally substituted with one, two, or three substituents independently selected from halo or —OR 9 ;
R d is hydrogen or C 1-6 alkyl which is optionally substituted with one, two, or three substituents independently selected from halo or —OR 9 ;
or R c and R d can be taken together with the nitrogen atom to which they are attached or are between them to form a C 3-8 heterocyclyl ring which is optionally substituted with one or two substituents independently selected from C 1-6 alkyl, halo hydroxyalkyl, hydroxy, alkoxy or keto;
n is independently selected from an integer from one to three;
each m is independently selected from an integer from zero to two;
and the pharmaceutically acceptable salts, stereoisomers and N-oxide derivatives thereof.
2 . The compound of claim 1 wherein R 1 is hydrogen and R 2 is hydrogen, or R 1 and R 2 can be taken together with the carbon atom to which they are attached to form a C 3-8 cycloalkyl ring wherein said ring system is optionally substituted with one or two substituents selected from C 1-6 alkyl or halo, and the pharmaceutically acceptable salts, stereoisomers and N-oxide derivatives thereof.
3 . The compound of claim 2 wherein R 3 is C 1-6 alkyl which is optionally substituted with one to six halo and R 4 is hydrogen, and the pharmaceutically acceptable salts, stereoisomers and N-oxide derivatives thereof.
4 . The compound of claim 3 wherein R 3 is n-propyl, isobutyl, 2-fluoro-2-methylpropyl, 2-trifluoromethylpropyl, 3-fluoro-2-(2-fluoromethyl)propyl, 2,2-difluoroethyl, 2,2-difluoropropyl, 3,3,3-trifluoropropyl, or 2,2-dichloroethyl and R 4 is hydrogen; and the pharmaceutically acceptable salts, stereoisomers and N-oxide derivatives thereof.
5 . The compound of claim 3 wherein R 5 is hydrogen and R 6 is aryl or heteroaryl wherein said aryl or heteroaryl are optionally substituted with one, two or three substituents selected from halo or —SO 2 R 12 ; and the pharmaceutically acceptable salts, stereoisomers and N-oxide derivatives thereof.
6 . The compound of claim 3 wherein R 5 is hydrogen and R 6 is C 1-6 alkyl substituted with 1-6 halo; and the pharmaceutically acceptable salts, stereoisomers and N-oxide derivatives thereof.
7 . The compound of claim 6 wherein R 5 is hydrogen and R 6 is trifluoromethyl or 3,3,3,2,2-pentafluoroethyl; and the pharmaceutically acceptable salts, stereoisomers and N-oxide derivatives thereof.
8 . The compound of claim 6 wherein n is two, each D is independently aryl or heteroaryl and R 7 is —SO m CH(R 10 )(R 11 ) or —SO m (R c )(R d ), R c and R d are each independently hydrogen or C 1-6 alkyl; and the pharmaceutically acceptable salts, stereoisomers and N-oxide derivatives thereof.
9 . The compound of claim 1 selected from:
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-phenylethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-fluoro-3-methylphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1R)-2,2,2-trifluoro-1-(4-pyridin-3-ylphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyridin-3-ylphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1R)-2,2,2-trifluoro-1-(4-pyridin-4-ylphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyridin-4-ylphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1R)-2,2,2-trifluoro-1-(4-{[4-(2-fluoroethyl)piperazin-1-yl]carbonyl}phenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-{[4-(2-fluoro ethyl)piperazin-1-yl]carbonyl}phenyl)ethyl]-L-leucinamide;
N 2 -[1-(1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(3-hydroxy-3-methylbut-1-ynyl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(3-hydroxy-3-methylbutyl)phenyl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2,3,3,3-pentafluoropropyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,3,3,3-pentafluoro-1-(4-pyridin-4-ylphenyl)propyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-fluoro-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[(1E)-3-hydroxy-3-methylbut-1-enyl]phenyl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]propyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]propyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1-oxidopyridin-3-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(morpholin-4-ylcarbonyl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-{[methoxy(methyl)amino]carbonyl}phenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-thien-3-ylphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(4-methylpyridin-2-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-methylpyridin-2-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(2′-fluoro-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-1-[4-(3,5-dimethylisoxazol-4-yl)phenyl]-2,2,2-trifluoroethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(hydroxymethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(4′-cyano-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-1-(3′,4′-difluoro-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-L-leucinamide;
4′-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-biphenyl-2-carboxylic acid methyl ester;
4′-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-biphenyl-3-carboxylic acid methyl ester;
N 1 -(cyanomethyl)-N 2 -[(1S)-1-(3′,4′-dimethoxy-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-(trifluoromethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-1-(3′,4′-dichloro-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(3′-formyl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-oxo-2,3-dihydro-1,3-benzothiazol-6-yl)phenyl]ethyl}-L-leucinamide;
N 2 -{(1S)-1-[4-(5-bromopyridin-3-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1H-indol-4-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyrimidin-5-ylphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-quinolin-3-ylphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;
4′-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-biphenyl-4-carboxylic acid methyl ester;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyrimidin-2-ylphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(3-methylpyridin-2-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(3-furyl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[3-(trifluoromethyl)pyridin-2-yl]phenyl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[4-(trifluoromethyl)pyridin-2-yl]phenyl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[5-(trifluoromethyl)pyridin-2-yl]phenyl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(3′-methoxy-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(3′-methoxy-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 2 -{(1S)-1-[4′-(acetylamino)-3′-fluoro-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(3-methylthien-2-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(3′-fluoro-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 2 -{(1S)-1-[4-(5-acetylthien-2-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -[(1S)-1-(3′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-(trifluoromethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(5′-fluoro-2′-methoxy-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-1-(3′,5′-difluoro-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(2′,3′,5′-trifluoro-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
3-(4′-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-biphenyl-3-yl)-acrylic acid;
N 2 -{(1S)-1-[4-(9-anthryl)phenyl]-2,2,2-trifluoroethyl}-N-1-(cyanomethyl)-L-leucinamide;
N 2 -[(1S)-1-(4′-benzoyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -[(1S)-1-(3′-acetyl-4′-hydroxy-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-1-[2′-(cyanomethyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(methylsulfinyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-morpholin-4-ylphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1R)-2,2,2-trifluoro-1-[4-(6-methylpyridin-3-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methylpyridin-3-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(5-phenylthien-2-yl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-quinolin-8-ylphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyridin-2-ylphenyl)ethyl]-L-leucinamide;
N 2 -{1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -{(1S)-1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1R)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(morpholin-4-ylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(isopropylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -{(1S)-1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -((1S)-1-{4′-[(acetylamino)sulfonyl]-1,1′-biphenyl-4-yl}-2,2,2-trifluoroethyl)-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-methyl-4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -[1-(5-bromothien-2-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -[1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;
4-(4′-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-biphenyl-4-yl)-piperazine-1-carboxylic acid tert-butyl ester;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4′-piperazin-1-yl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4′-[4-(2-hydroxyethyl)piperazin-1-yl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4′-[4-(2-hydroxy-2-methylpropyl)piperazin-1-yl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -(1-{4-[(dimethylamino)carbonyl]phenyl}-2,2,2-trifluoroethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4′-piperazin-1-yl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -(1-{4-[(cyclopropylamino)carbonyl]phenyl}-2,2,2-trifluoroethyl)-L-leucinamide;
4-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-benzoic acid;
N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4′-[4-(2-fluoroethyl)piperazin-1-yl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-{[4-(2-hydroxy-2-methylpropyl)piperazin-1-yl]carbonyl}phenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methyl-1,3-thiazol-4-yl)phenyl]ethyl}-L-leucinamide;
N 2 -{1-[4-(3-tert-butyl-1,2,4-triazin-5-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-{2-[3-(methylsulfonyl)phenyl]-1,3-thiazol-4-yl}phenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[2-(1H-pyrazol-4-yl)-1,3-thiazol-4-yl]phenyl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4′-[4-(methylsulfonyl)piperazin-1-yl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;
N 2 -[1-(3-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-3-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(3-pyridin-4-ylphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4′-piperazin-1-yl-1,1′-biphenyl-3-yl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-3-yl]ethyl}-L-leucinamide;
N-(cyanomethyl)-1-[(2,2,2-trifluoro-1-phenylethyl)amino]cyclohexanecarboxamide;
1-{[1-(4-bromophenyl)-2,2,2-trifluoroethyl]amino}-N-(cyanomethyl)cyclohexanecarboxamide;
N-(cyanomethyl)-1-{[2,2,2-trifluoro-1-(4′-piperazin-1-yl-1,1′-biphenyl-4-yl)ethyl]amino}cyclohexanecarboxamide;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-piperidin-4-ylphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(4-pyridin-2-ylpiperazin-1-yl)phenyl]ethyl}-L-leucinamide;
N 2 -[1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-3-cyclopropylalaninamide;
N 1 -(cyanomethyl)-3-cyclopropyl-N 2 -[2,2,2-trifluoro-1-(4-pyridin-4-ylphenyl)ethyl]alaninamide;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4′-pyridin-4-yl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1R)-2,2,2-trifluoro-1-(1,3-thiazol-2-yl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-methoxy-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-methoxyphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-pyridin-4-yl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-phenoxyphenyl)ethyl]-L-leucinamide;
N 2 -[(1S)-1-(4′-bromo-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -{(1S)-1-[4-(4-chloropyridin-3-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -{(1S)-1-[4′-(acetylamino)-2′-methyl-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -[(1S)-1-(1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methoxypyridin-3-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methoxypyridin-2-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4″-(methylsulfonyl)-1,1′:4′,1″-terphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-3-(1-methylcyclopropyl)-L-alaninamide;
N 1 -(cyanomethyl)-3-(1-methylcyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-alaninamide;
N 1 -(cyanomethyl)-3-(1-methylcyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-alaninamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-methyl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(hydroxymethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -[1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-D-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-D-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(morpholin-4-ylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-D-leucinamide;
N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4′-[(methylamino)sulfonyl]-1,1′-biphenyl-4-yl}ethyl)-D-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1R)-2,2,2-trifluoro-1-[4-(1-oxidopyridin-4-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(1-oxidopyridin-4-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4-[6-(1-hydroxy-1-methylethyl)-1-oxidopyridin-3-yl]phenyl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4-[6-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4-[2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]phenyl}ethyl)-L-leucinamide;
N 2 -[1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-piperazin-1-ylphenyl)ethyl]-L-leucinamide;
N 2 -{1-[3′-(acetylamino)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(4-propylpiperazin-1-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(piperazin-1-ylcarbonyl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trifluoro-1-(4-{[4-(2-hydroxyethyl)piperazin-1-yl]carbonyl}phenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-{3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}phenyl)ethyl]-L-leucinamide;
4-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-benzoic acid methyl ester;
N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[(E)-2-quinolin-2-ylethenyl]phenyl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]ethyl}-L-leucinamide;
N 2 -((1S)-1-{4-[3-(5-bromopyridin-3-yl)-1,2,4-oxadiazol-5-yl]phenyl}-2,2,2-trifluoroethyl)-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -[(1S)-1-(4-benzoylphenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(thien-2-ylcarbonyl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1,3-thiazol-2-ylcarbonyl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-{(Z)-2-[4-(methylsulfonyl)phenyl]ethenyl}phenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-{(E)-2-[4-(methylsulfonyl)phenyl]ethenyl}phenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-isobutyrylphenyl)ethyl]-L-leucinamide;
N 2 -{(1S)-1-[4-(4-bromo-1,3-thiazol-2-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-1-(4-cyanophenyl)-2,2,2-trifluoroethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-1-(4-ethynylphenyl)-2,2,2-trifluoroethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(2′-fluoro-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(2-methylquinolin-7-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(1H-indol-5-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{1-[4′-(dimethylamino)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-1-(4-{[(cyanomethyl)amino]carbonyl}phenyl)-2,2,2-trifluoroethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1R)-1-(4-{[(cyanomethyl)amino]carbonyl}phenyl)-2,2,2-trifluoroethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[3′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
4′-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-biphenyl-4-carboxylic acid;
4′-{1-[1-(Cyanomethyl-carbamoyl)-3-methyl-butylamino]-2,2,2-trifluoro-ethyl}-biphenyl-4-carboxylic acid methoxy-methyl-amide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-({[4-(methylsulfonyl)benzyl]thio}methyl)phenyl]ethyl}-L-leucinamide;
N 2 -{(1S)-1-[4-(5-chloropyridin-2-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -{(1S)-1-[3′-(aminosulfonyl)-4′-bromo-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -{(1S)-1-[4′-bromo-3′-(methylsulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[5-methyl-6-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)-L-leucinamide;
N 2 -[(1S)-1-(4-{5-chloro-3-[4-(methylsulfonyl)phenyl]pyridin-2-yl}phenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[(phenylthio)methyl]phenyl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(trifluoromethyl)sulfonyl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-{[(4-fluorobenzoyl)amino]methyl}phenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(methylsulfonyl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-1-[4′-(ethylsulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-L-leucinamide;
N 2 -((1S)-1-{4-[({[3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4-yl]carbonyl}amino)methyl]phenyl}-2,2,2-trifluoroethyl)-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -((1S)-1-{4-[(9-chloro-3-methyl-4-oxoisoxazolo[4,3-c]quinolin-5(4H)-yl)methyl]phenyl}-2,2,2-trifluoroethyl)-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-methoxy-3′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -{(1S)-1-[4″-chloro-4′-(methylsulfonyl)-1,1′:2′,1″-terphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-methoxy-4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -{(1S)-1-[2′-chloro-4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(2-hydroxyethyl)thio]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-fluoro-4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(2-hydroxyethyl)sulfonyl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-({2-[methoxy(methyl)amino]-2-oxoethyl}sulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(2-hydroxy-2-methylpropyl)sulfonyl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;
N 2 -{(1S)-1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 2 -[(4-bromophenyl)(2,4,6-trifluorophenyl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(4-pyridin-4-ylphenyl)(2,4,6-trifluorophenyl)methyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[[4-(4-fluorobenzyl)phenyl](phenyl)methyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{phenyl[4-(pyridin-3-ylmethyl)phenyl]methyl}-L-leucinamide;
N 2 -{(4-bromophenyl)[4-(methylsulfonyl)phenyl]methyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{[4-(methylsulfonyl)phenyl][4′-(methylthio)-1,1′-biphenyl-4-yl]methyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl][4-(methylsulfonyl)phenyl]methyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[2,2,2-trichloro-1-(4-glycoloylphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[2-fluoro-1-(fluoromethyl)-1-phenylethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(pyrrolidin-1-ylacetyl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4-(piperazin-1-ylcarbonyl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -(2,2,2-trifluoro-1-{4-[2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]phenyl}ethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-3-(1-methylcyclopropyl)-N 2 -(2,2,2-trifluoro-1-{4-[1-(2-hydroxyethyl)prolyl]phenyl}ethyl)-L-alaninamide;
N 2 -[[4-(4-tert-butylpiperazin-1-yl)phenyl](pentafluorophenyl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;
N-(cyanomethyl)-1-{1-[4-(4-methylpiperazin-1-yl)phenyl]ethyl}piperidine-2-carboxamide;
N 2 -[[4-(4-tert-butylpiperazin-1-yl)phenyl](pyridin-2-yl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -{[4-(4-tert-butylpiperazin-1-yl)phenyl][5-(trifluoromethyl)pyridin-2-yl]methyl}-N 1 -(cyanomethyl)-L-leucinamide;
(4S)—N-(cyanomethyl)-4-methyl-1-[(1S)-1-(4-piperazin-1-ylphenyl)ethyl]-L-prolinamide;
(4S)—N-(cyanomethyl)-4-methyl-1-[(1R)-1-(4-piperazin-1-ylphenyl)ethyl]-L-prolinamide;
N-(cyanomethyl)-1-[(1S)-1-(4-piperazin-1-ylphenyl)ethyl]-L-prolinamide;
N-(cyanomethyl)-1-[(1R)-1-(4-piperazin-1-ylphenyl)ethyl]-L-prolinamide;
N-(cyanomethyl)-4,4-difluoro-1-[(1S)-1-(4-piperazin-1-ylphenyl)ethyl]-L-prolinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-methylphenyl)ethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1H-pyrazol-3-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methyl-1,3-oxazol-4-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyrazin-2-ylphenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methylpyridin-4-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(4-methylpyridin-3-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1H-pyrazol-4-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyridin-4-ylphenyl)ethyl]-L-leucinamide;
N 2 -[(1S)-1-(3′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(3′-fluoro-4′-methyl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -((1S)-2,2,2-trifluoro-1-{5-[4-(1-hydroxy-1-methylethyl)phenyl]pyridin-2-yl}ethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]propyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,3,3,3-pentafluoro-1-(4′-methyl-1,1′-biphenyl-4-yl)propyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4-(6-methoxypyridin-3-yl)phenyl]propyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,3,3,3-pentafluoro-1-(2′-fluoro-1,1′-biphenyl-4-yl)propyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-methoxy-3′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -{(1S)-1-[3′-(aminosulfonyl)-4′-methoxy-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methoxypyridin-3-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4-(5-methylpyridin-2-yl)phenyl]propyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[5-(methylsulfonyl)pyridin-2-yl]phenyl}ethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-methylpyridin-2-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-methyl-4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[5-(1H-pyrazol-3-yl)pyridin-2-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(5-quinolin-5-ylpyridin-2-yl)ethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(5-quinolin-6-ylpyridin-2-yl)ethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2-difluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,3,3,3-pentafluoropropyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 2 -[(1S)-1-(1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 2 -{(1S)-1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,3,3,3-pentafluoropropyl}-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(1-ethoxyvinyl)phenyl]-2,2,2-trifluoroethyl}-L-leucinamide;
N 2 -[(1S)-1-(4-acetylphenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-isopropylphenyl)ethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-phenylethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1-hydroxy-1-methylethyl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1-methylcyclopropyl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(2′,4′,6′-trimethyl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 2 -[(1S)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 2 -{(1S)-1-[5-(4-acetylphenyl)pyridin-2-yl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 2 -{(1S)-1-[6-(4-acetylphenyl)pyridin-3-yl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 2 -{(1S)-1-[5-(3-acetylphenyl)pyridin-2-yl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -((1S)-2,2,2-trifluoro-1-{5-[4-(1-hydroxyethyl)phenyl]pyridin-2-yl}ethyl)-L-leucinamide;
N 2 -[(1S)-1-(1,1′-biphenyl-4-yl)-2,2,3,3,3-pentafluoropropyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,3,3,3-pentafluoropropyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -[(1S)-1-(1,1′-biphenyl-4-yl)-2,2,3,3,3-pentafluoropropyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 2 -(1-benzyl-2,2,2-trifluoroethyl)-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 2 -[(1S)-1-(4-tert-butylphenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-4-methyl-L-leucinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-methyl-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4-[2-(1H-pyrazol-4-yl)-1,3-thiazol-4-yl]phenyl}ethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methyl-1,3-thiazol-4-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methylpyridin-4-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methylpyridin-3-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methylpyridin-2-yl)phenyl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(3′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1H-pyrazol-3-yl)phenyl]ethyl}-L-leucinamide;
N 1 -[(1S)-1-cyanoethyl]-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -[(1S)-1-cyano-3-(methylthio)propyl]-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -[(1S)-1-cyano-3-(methylsulfonyl)propyl]-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2,3,3,3-pentafluoropropyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4-(6-methoxypyridin-2-yl)phenyl]propyl}-L-leucinamide;
N 2 -[(1S)-1-(5-bromopyridin-2-yl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -((1S)-2,2,2-trifluoro-1-{5-[4-(methylsulfonyl)phenyl]pyridin-2-yl}ethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(6′-methyl-3,3′-bipyridin-6-yl)ethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methoxypyridin-2-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-oxo-1,6-dihydropyridin-2-yl)phenyl]ethyl}-L-leucinamide;
(4S)—N 1 -(cyanomethyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
(4S)—N 1 -(1-cyanocyclopropyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
(4S)—N 1 -(cyanomethyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
(4S)—N 1 -(1-cyanocyclopropyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
(4S)—N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-5,5,5-trifluoro-L-leucinamide;
(4S)—N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-5,5,5-trifluoro-L-leucinamide;
N 2 -{(1S)-1-[4-(6-aminopyridin-3-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4-(6-methylpyridin-3-yl)phenyl]propyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4-(6-methylpyridin-3-yl)phenyl]propyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methylpyridin-3-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(2,2,2-trifluoro-1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]propyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]propyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]propyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4-(6-methoxypyridin-2-yl)phenyl]propyl}-L-leucinamide;
(4R)—N 1 -(cyanomethyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
(4R)—N 1 -(1-cyanocyclopropyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(1S)-2,2,3,3,3-pentafluoro-1-(4′-methyl-1,1′-biphenyl-4-yl)propyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4-(1,3-thiazol-2-yl)phenyl]propyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-1-(4-ethynylphenyl)-2,2,3,3,3-pentafluoropropyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-1-[4-(cyclopropylethynyl)phenyl]-2,2,2-trifluoroethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(cyclopropylethynyl)phenyl]-2,2,2-trifluoroethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-methyl-1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-methyl-1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(cyclopropylethynyl)phenyl]-2,2,3,3,3-pentafluoropropyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(4-methyl-1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(4-methyl-1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-1-[4-(4,5-dimethyl-1,3-thiazol-2-yl)phenyl]-2,2,2-trifluoroethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4′-(ethylsulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyridin-3-ylphenyl)ethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-methoxy-3′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-alaninamide;
N 2 -{(1S)-1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,3,3,3-pentafluoropropyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -((1S)-2,2,3,3,3-pentafluoro-1-{4′-[(2-hydroxy-2-methylpropyl)sulfonyl]-1,1′-biphenyl-4-yl}propyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-alaninamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,3,3,3-pentafluoro-1-[4′-(isopropylsulfonyl)-1,1′-biphenyl-4-yl]propyl}-L-leucinamide;
N 1 -(1-cyano-1-methylethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(2-hydroxy-2-methylpropyl)sulfonyl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-methyl-4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4′-(ethylsulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-L-leucinamide;
N 2 -{(1S)-1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(S)[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl][4-(trifluoromethoxy)phenyl]methyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(S)-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl](thien-2-yl)methyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(S)-(4′-piperazin-4-ium-1-yl-1,1′-biphenyl-4-yl)(thien-2-yl)methyl]-L-leucinamide methanesulfonate;
N 1 -(cyanomethyl)-N 2 -{(S)-(4-fluorophenyl)[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]methyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(S)[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl][4-(trifluoromethyl)phenyl]methyl}-L-leucinamide;
N 2 -{(S)-(4-chlorophenyl)[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]methyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 2 -[(S)-(4-bromophenyl)(thien-2-yl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(S)-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl](thien-2-yl)methyl]-L-leucinamide;
N 2 -{(R)-(4-bromophenyl) [4-(trifluoromethoxy)phenyl]methyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(S)-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl][4-(trifluoromethoxy)phenyl]methyl}-L-leucinamide;
N 2 -[(S)-(4-bromophenyl)(2-furyl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(S)-2-furyl[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]methyl}-L-leucinamide;
N 2 -[1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-L-norvalinamide;
N 2 -{(R)-(4-bromophenyl) [4-(trifluoromethyl)phenyl]methyl}-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{1-[4′-(4-cyclopropylpiperazin-1-yl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-L-norvalinamide;
N 2 -[(R)-(4-bromophenyl)(4-chlorophenyl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 2 -[(S)-(4-bromophenyl)(3-methylthien-2-yl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -[(S)-(4-bromophenyl)(thien-3-yl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(S)-(2,4-difluorophenyl)[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]methyl}-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(S)-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl](thien-3-yl)methyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(S)-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl](3-methylthien-2-yl)methyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(S)-[4′-(4-cyclopropylpiperazin-1-yl)-1,1′-biphenyl-4-yl](3-methylthien-2-yl)methyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -[(S)-[4′-(4-cyclopropylpiperazin-1-yl)-1,1′-biphenyl-4-yl](thien-3-yl)methyl]-L-leucinamide;
N 2 -[1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-5,5,5-trifluoro-L-norvalinamide;
N 1 -(cyanomethyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 2 -[(S)-(4-bromophenyl)(3-methylthien-2-yl)methyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -[(S)-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl](3-methylthien-2-yl)methyl]-L-leucinamide;
N 1 -(cyanomethyl)-N 2 -{(S)-3-furyl[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]methyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-norvalinamide N 2 -[(S)-(4-bromophenyl)(4-bromothien-2-yl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 2 -[(S)-(4-bromophenyl)(thien-3-yl)methyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(cyanomethyl)-N 2 —((S)-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]{4-[4-(methylsulfonyl)phenyl]thien-2-yl}methyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -[(S)-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl](thien-3-yl)methyl]-L-leucinamide;
N 2 -{(1S)-1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-L-norvalinamide;
N 2 -[(S)-(4-bromophenyl)(4-bromothien-2-yl)methyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 2 -[(S)-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl](thien-3-yl)methyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 2 -[(S)-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl](thien-3-yl)methyl]-N 1 -(cyanomethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-methoxy-3′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methylpyridin-4-yl)phenyl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-5,5,5-trifluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1H-pyrazol-3-yl)phenyl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-methylpyridin-2-yl)phenyl]ethyl}-L-norvalinamide;
2-{[(4-Bromo-phenyl)-pyridin-4-yl-methyl]-amino}-pentanoic acid cyanomethyl-amide;
2-{[(4-Bromo-phenyl)-thiazol-2-yl-methyl]-amino+}-pentanoic acid cyanomethyl-amide;
(2S)-2-[(S)-1-(4′-Acetylbiphenyl-4-yl)-2,2,2-trifluoroethylamino]-pentanoic acid (1-cyanocyclopropyl)-amide;
(2S)-2-[(S)-1-(2′,4′-Difluorobiphenyl-4-yl)-2,2,2-trifluoroethylamino]-pentanoic acid (1-cyanocyclopropyl)-amide;
(2S)-2-[(S)-1-(3′,4′-Difluorobiphenyl-4-yl)-2,2,2-trifluoroethylamino]-pentanoic acid (1-cyanocyclopropyl)-amide;
(2S)-2-[(S)-1-(3′-Chloro-4′-fluorobiphenyl-4-yl)-2,2,2-trifluoroethylamino]-pentanoic acid (1-cyano-cyclopropyl)-amide;
(2S)-2-[(S)-2,2,2-Trifluoro-1-(4′-methanesulfonylamino-biphenyl-4-yl)-ethylamino]-pentanoic acid (1-cyano-cyclopropyl)-amide;
(2S)-2-{(S)-[(4-Bromo-phenyl)-thiazol-2-yl-methyl]-amino}-4-methylpentanoic acid cyanomethyl-amide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-chloro-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-chloro-3′-methyl-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-chloro-2′-methyl-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
(2S)-2-{(S)-2,2,2-Trifluoro-1-[4-(1H-indol-5-yl)-phenyl]-ethylamino}-pentanoic acid (1-cyano-cyclopropyl)-amide;
(2S)-2-[(S)-2,2,2-Trifluoro-1-(3′-methanesulfonylamino-biphenyl-4-yl)-ethylamino]-pentanoic acid (1-cyano-cyclopropyl)-amide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-fluoro-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-fluoro-3′-methyl-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-fluoro-4′-methyl-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-trifluoromethoxy-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
(2S)-2-[(S)-2,2,2-Trifluoro-1-(4′-methylbiphenyl-4-yl)-ethylamino]-pentanoic acid (1-cyanocyclopropyl)-amide;
(2S)-2-[(S)-1-(4′-Cyanobiphenyl-4-yl)-2,2,2-trifluoroethylamino]-pentanoic acid (1-cyanocyclopropyl)-amide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-methoxy-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(benzo[1,3]dioxol-5-yl)phenyl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methoxycarbonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
(2S)-2-{(S)-[(4-Bromophenyl)-thiazol-2-yl-methyl]-amino}-4-methylpentanoic acid (1-cyanocyclopropyl)-amide;
(2S)-2-{(S)-[(4′-Methanesulfonyl-biphenyl-4-yl)-thiazol-2-yl-methyl]-amino}-4-methyl-pentanoic acid cyanomethyl-amide;
(2S)-2-[(S)-2,2,2-Trifluoro-1-(4′-trifluoromethyl-biphenyl-4-yl)-ethylamino]-pentanoic acid (1-cyano-cyclopropyl)-amide;
(2S)-2-[(S)-2,2,2-Trifluoro-1-(2′-trifluoromethyl-biphenyl-4-yl)-ethylamino]-pentanoic acid (1-cyano-cyclopropyl)-amide;
(2S)-2-{(S)-[(2′,4′-Difluorobiphenyl-4-yl)-thiazol-2-yl-methyl]-amino}-4-methylpentanoic acid (1-cyanocyclopropyl)-amide;
(2S)-2-{(S)-[(4′-Methanesulfonylbiphenyl-4-yl)-thiazol-2-yl-methyl]-amino}-4-methylpentanoic acid (1-cyanocyclopropyl)-amide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1-oxido-2,3-dihydro-1-benzothien-5-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(1,1-dioxido-2,3-dihydro-1-benzothien-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(1,1-dioxido-2,3-dihydro-1,2-benzisothiazol-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulflnyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(1,1-dioxido-3-oxo-2,3-dihydro-1,2-benzisothiazol-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(cyanomethyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(cyanomethyl)-4-fluoro-N 2 -{(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(cyanomethyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
(2S)—N-(cyanomethyl)-4,4-difluoro-2-({(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;
(2S)—N-(1-cyanocyclopropyl)-4,4-difluoro-2-{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;
(2S)—N-(1-cyanocyclopropyl)-4,4-difluoro-2-{(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;
(2S)—N-(cyanomethyl)-4,4-difluoro-2-{(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;
(2S)-4,4-dichloro-N-(cyanomethyl)-2-({(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;
(2S)-4,4-dichloro-N-(1-cyanocyclopropyl)-2-{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;
(2S)-4,4-dichloro-N-(1-cyanocyclopropyl)-2-{(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;
(2S)-4,4-dichloro-N-(cyanomethyl)-2-({(1S)-2,2,2-trichloro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}amino)butanamide;
N 2 -[(1S)-1-(1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-(1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-methyl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;
N 2 -[(1S)-1-(2′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-(1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[2′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{5-[4-(methylsulfonyl)phenyl]pyridin-2-yl}ethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{6-[4-(methylsulfonyl)phenyl]pyridin-3-yl}ethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-{6-[(methylsulfonyl)amino]pyridin-3-yl}phenyl)ethyl]-L-leucinamide;
N 1 -(cyanomethyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-{6-[(methylsulfonyl)amino]pyridin-3-yl}phenyl)ethyl]-L-leucinamide;
N 1 -(1-cyanobutyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyano-2-cyclopropylethyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyano-2-pyridin-3-ylethyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyano-3-hydroxy-3-methylbutyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(3,3-dimethyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(3,3-diethyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(3-oxo-1,3-dihydro-2-benzofuran-5-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(1,1-dimethyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(1,1-diethyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(3-oxo-1,3-dihydro-2-benzofuran-5-yl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4′-(1,1-dimethyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4′-(1,1-diethyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4′-(3,3-dimethyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4′-(3,3-diethyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-oxo-2,5-dihydrofuran-3-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(2,2-dimethyl-5-oxo-2,5-dihydrofuran-3-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(2,2-diethyl-5-oxo-2,5-dihydrofuran-3-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-oxo-2,5-dihydrofuran-3-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(5,5-dimethyl-2-oxo-2,5-dihydrofuran-3-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(5,5-diethyl-2-oxo-2,5-dihydrofuran-3-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-oxo-4-oxaspiro[2.4]hept-6-en-7-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-oxo-5-oxaspiro[3.4]oct-7-en-8-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-oxo-4-oxaspiro[2.4]hept-6-en-6-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-oxo-5-oxaspiro[3.4]oct-7-en-7-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-quinolin-6-ylphenyl)ethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulflnyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-quinolin-6-ylphenyl)ethyl]-L-leucinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4,4-difluoro-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -[(1S)-1-cyano-3-(methylsulfonyl)propyl]-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-quinolin-6-ylphenyl)ethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulflnyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-quinolin-6-ylphenyl)ethyl]-L-leucinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4,4-difluoro-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{4-[5-methyl-6-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{4-[6-(1-hydroxy-1-methylethyl)-5-methylpyridin-3-yl]phenyl}ethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-fluoro-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-methyl-4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methylpyridin-3-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methylquinolin-7-yl)phenyl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-4,4-difluoro-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(1S)-1-hydroxyethyl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(1R)-1-hydroxyethyl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(trifluoroacetyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[5-(2-naphthyl)pyridin-2-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(cyanomethyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-methyl-1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(1,1-dioxido-3-oxo-2,3-dihydro-1,2-benzisothiazol-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 2 -[(4-bromophenyl)(phenyl)methyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-methyl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 2 -[(1S)-1-(1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;
N 2 -{(1S)-1-[4-(5-chloropyridin-2-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyridin-4-ylphenyl)ethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(methylsulfonyl)amino]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2-difluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2-difluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyrimidin-5-ylphenyl)ethyl]-L-leucinamide;
N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-(1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2-difluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(3,5-dimethylisoxazol-4-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 1 -[(1S)-1-cyano-3-(methylsulfonyl)propyl]-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-quinolin-6-ylphenyl)ethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulflnyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -[(1S)-2,2,2-trifluoro-1-(4-quinolin-6-ylphenyl)ethyl]-L-leucinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4,4-difluoro-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{4-[5-methyl-6-(methylsulfonyl)pyridin-3-yl]phenyl}ethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{4-[6-(1-hydroxy-1-methylethyl)-5-methylpyridin-3-yl]phenyl}ethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-fluoro-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-methyl-4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(6-methylpyridin-3-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(1-hydroxy-1-methylethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(2-methylquinolin-7-yl)phenyl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(cyanomethyl)-4,4-difluoro-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(1S)-1-hydroxyethyl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(1R)-1-hydroxyethyl]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(trifluoroacetyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2,2-trifluoro-1-[5-(2-naphthyl)pyridin-2-yl]ethyl}-L-leucinamide;
N 1 -(cyanomethyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(cyanomethyl)-4,4-difluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-norvalinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4-(5-methyl-1,3-thiazol-2-yl)phenyl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(1,1-dioxido-3-oxo-2,3-dihydro-1,2-benzisothiazol-5-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
N 2 -[(4-bromophenyl)(phenyl)methyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4′-methyl-1,1′-biphenyl-4-yl)ethyl]-L-leucinamide;
N 2 -[(1S)-1-(1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;
N 2 -{(1S)-1-[4-(5-chloropyridin-2-yl)phenyl]-2,2,2-trifluoroethyl}-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyridin-4-ylphenyl)ethyl]-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -((1S)-2,2,2-trifluoro-1-{4′-[(methylsulfonyl)amino]-1,1′-biphenyl-4-yl}ethyl)-L-leucinamide;
N 2 -[(1S)-1-(4-bromophenyl)-2,2-difluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-2,2-difluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -[(1S)-2,2,2-trifluoro-1-(4-pyrimidin-5-ylphenyl)ethyl]-L-leucinamide;
N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[3′-(1-hydroxyethyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide;
N 2 -[(1S)-1-(4′-acetyl-1,1′-biphenyl-4-yl)-2,2-difluoroethyl]-N 1 -(1-cyanocyclopropyl)-L-leucinamide;
N 1 -(1-cyanocyclopropyl)-N 2 -{(1S)-1-[4-(3,5-dimethylisoxazol-4-yl)phenyl]-2,2,2-trifluoroethyl}-4-fluoro-L-leucinamide;
and the pharmaceutically acceptable salts, stereoisomers and N-oxide derivatives thereof.
10 . N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide or a pharmaceutically acceptable salt thereof.
11 . N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylsulfinyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide or a pharmaceutically acceptable salt thereof.
12 . N 1 (cyanomethyl)-N 2 {(1S)-2,2,2-trifluoro-1-[4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide or a pharmaceutically acceptable salt thereof.
13 . N 2 {(1S)-1-[4′-(aminosulfonyl)-1,1′-biphenyl-4-yl]-2,2,2-trifluoroethyl}-N 1 (cyanomethyl)-L-leucinamide or a pharmaceutically acceptable salt thereof.
14 . A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.
15 . A pharmaceutical composition made by combining a compound according to claim 1 and a pharmaceutically acceptable carrier.
16 . A process for making a pharmaceutical composition comprising combining a compound according to claim 1 and a pharmaceutically acceptable carrier.
17 . A method of inhibiting cathepsin activity in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of a compound according to claim 1 .
18 . The method according to claim 17 wherein the cathepsin activity is Cathepsin K activity.
19 . A method of treating or preventing a disease selected from: osteoporosis, glucocorticoid induced osteoporosis, Paget's disease, abnormally increased bone turnover, periodontal disease, tooth loss, bone fractures, rheumatoid arthritis, osteoarthritis, periprosthetic osteolysis, osteogenesis imperfecta, metastatic bone disease, hypercalcemia of malignancy or multiple myeloma in a mammal in need thereof by administering to the mammal a therapeutically effective amount of a compound according to claim 1 .
20 . The method of claim 19 wherein the disease is osteoporosis.
21 . A method of treating cathepsin dependent conditions in a mammal in need thereof by administering to the mammal a therapeutically effective amount of a compound according to claim 1 .
22 . A pharmaceutical composition comprising a compound of claim 1 and another agent selected from: an organic bisphosphonate, an estrogen receptor modulator, an estrogen receptor beta modulator, an androgen receptor modulator, an inhibitor of osteoclast proton ATPase, an inhibitor of HMG-CoA reductase, an integrin receptor antagonist, or an osteoblast anabolic agent, and the pharmaceutically acceptable salts and mixtures thereof.
23 . A method of treating or preventing a disease selected from: osteoporosis, glucocorticoid induced osteoporosis, Paget's disease, abnormally increased bone turnover, periodontal disease, tooth loss, bone fractures, rheumatoid arthritis, osteoarthritis, periprosthetic osteolysis, osteogenesis imperfecta, metastatic bone disease, hypercalcemia of malignancy or multiple myeloma comprising a compound of claim 1 and another agent selected from: an organic bisphosphonate, an estrogen receptor modulator, an androgen receptor modulator, an inhibitor of osteoclast proton ATPase, an inhibitor of HMG-CoA reductase, an integrin receptor antagonist, or an osteoblast anabolic agent, and the pharmaceutically acceptable salts and mixtures thereof.
24 . The method of claim 23 wherein the disease is osteoporosis.
25 . A pharmaceutical composition comprising a compound of claim 1 and another agent selected from: an organic bisphosphonate, an estrogen receptor modulator, an estrogen receptor beta modulator, an androgen receptor modulator, an inhibitor of osteoclast proton ATPase, an inhibitor of HMG-CoA reductase, an integrin receptor antagonist, or an osteoblast anabolic agent, and the pharmaceutically acceptable salts and mixtures thereof.
26 . A method of inhibiting bone resorption with a compound according to claim 1 .
27 . A method of increasing bone mineral density with a compound according to claim 1 .
28 . A method of reducing the risk of fractures with a compound of claim 1 .
29 . (2S)-2-{[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]amino}-4-fluoro-4-methyl-pentan-1-ol.
30 . N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide or a pharmaceutically acceptable salt thereof.
31 . The compound of claim 30 which is N 2 -[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N 1 -(1-cyanocyclopropyl)-4-fluoro-L-leucinamide.
32 . N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide or a pharmaceutically acceptable salt thereof.
33 . The compound of claim 32 which is N 1 -(1-cyanocyclopropyl)-4-fluoro-N 2 -{(1S)-2,2,2-trifluoro-1-[4′-(methylthio)-1,1′-biphenyl-4-yl]ethyl}-L-leucinamide.Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.