IP Library › Granted Patent US 7,205,306

Granted Patent B2

US 7,205,306 · App. 10/145,440 · Granted Apr 17, 2007

Substituted pyrazinones, pyridines and pyrimidines as corticotropin releasing factor ligands

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Quick Facts

Patent No.: US 7,205,306
App. No.: 10/145,440
Granted: Apr 17, 2007
Kind: B2

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Abstract

Compounds provided herein are novel substituted pyrazinones, pyridines and pyrimidines of Formula (I) and (II): Such compounds are particularly useful as CRF receptor ligands, and hence, in the treatment of various neurologically-related disorders such as affective disorder, anxiety and depression.

Claims (355)

1. A compound of Formula (I) or (II):

or a pharmaceutically acceptable salt form thereof, wherein:

X is N or CR 1 ;

provided that when X is N, R 1 can not be either —NR 9 R 10 or —NR 9 COR 9 ;

W is ═O, ═S, —H or (—H, —H);

Y is —C(═O)—, —C(R Y ) 2 —, or —CH═;

R Y is independently, at each occurrence, selected from H, methyl, ethyl, and C 1 –C 2 haloalkyl;

B is R 3 , NHR 3 , NR 3 R 1 , OR 3 , or SO n R 3 ;

R 1 is independently, at each occurrence, selected from H, halogen, —CN, C 1 –C 4 haloalkyl, —NR 9 R 10 , —NR 9 COR 9 , —COR 10 , —OR 10 , SH, —S(O) n R 12 , C 1 –C 6 alkyl, C 2 –C 6 alkenyl, C 2 –C 6 alkynyl, C 3 –C 6 cycloalkyl, and C 4 –C 8 cycloalkylalkyl;

wherein each C 1 –C 6 alkyl, C 2 –C 6 alkenyl, C 2 –C 6 alkynyl, C 3 –C 6 cycloalkyl, or C 4 –C 8 cycloalkylalkyl is each optionally substituted with halogen, CN, C 1 –C 4 haloalkyl, —NR 9 R 10 , —NR 9 COR 9 , —COR 10 , —OR 10 , SH or —S(O) n R 12 ;

R 2 is H, halogen, CN, C 1 –C 4 haloalkyl, —NR 9 R 10 , NR 9 COR 9 , —COR 10 , —OR 10 , SH, —S(O) n R 12 , C 1 –C 4 alkyl, C 3 –C 6 cycloalkyl, or C 4 –C 8 cycloalkylalkyl;

wherein each C 1 –C 4 alkyl, C 3 –C 6 cycloalkyl, or C 4 –C 8 cycloalkylalkyl is optionally substituted with halogen, —CN, C 1 –C 4 haloalkyl, —NR 9 R 10 , —NR 9 COR 9 , —COR 10 , —OR 10 , SH or —S(O) n R 12 ;

R 2a is H, F, Cl, Br, —CN, —OH, methyl, ethyl, propyl, cyclopropyl, cyclobutyl, methoxy, ethoxy, propoxy, C 1 –C 3 alkoxy, cyclopropyloxy-, —OCF 3 , —CF 3 , —CO 2 CH 3 , —CO 2 CH 2 CH 3 , —C(O)CH 3 , —C(O)CH 2 CH 3 , —CH 2 OH, —CH 2 OCH 3 , —CH 2 OCH 2 CH 3 , —C(O)NH 2 , —C(O)N(H)CH 3 , —C(O)N(H)CH 2 CH 3 , —C(O)N(CH 3 ) 2 , —C(O)N(CH 3 )CH 2 CH 3 , —C(O)N(CH 2 CH 3 ) 2 , —S(O) 2 N(CH 3 ) 2 , —S(O) 2 N(CH 3 )CH 2 CH 3 , —S(O) 2 N(CH 2 CH 3 ) 2 , —S(O) 2 CH 3 , —S(O) 2 CH 2 CH 3 , —NH 2 , —N(H)CH 3 , —N(H)CH 2 CH 3 , —N(CH 3 ) 2 , —N(CH 3 )CH 2 CH 3 , —N(CH 2 CH 3 ) 2 , or —N(H)CF 3 ;

R 3 is C 1 –C 10 alkyl, C 3 –C 10 alkenyl, C 3 –C 10 alkynyl, C 3 –C 8 cycloalkyl, C 4 –C 12 cycloalkylalkyl, C 2 –C 10 alkoxyalkyl, C 5 –C 10 cycloalkenyl, or C 6 –C 10 cycloalkenylalkyl;

wherein one carbon in any cycloalkyl ring may be replaced with O, S or NR 9 ; and

wherein each C 1 –C 10 alkyl, C 3 –C 10 alkenyl, C 3 –C 8 alkynyl, C 3 –C 8 cycloalkyl, C 4 –C 12 cycloalkylalkyl, C 2 –C 10 alkoxyalkyl, C 5 –C 10 cycloalkenyl, or C 6 –C 10 cycloalkenylalkyl is optionally substituted with 1, 2 or 3 substituents independently selected at each occurrence from C 1 –C 6 alkyl, C 2 –C 6 alkenyl, C 2 –C 10 alkynyl, C 3 –C 6 cycloalkyl, halogen, C 1 –C 4 haloalkyl, cyano, —OR 7 , SH, —S(O) n R 11 , —COR 6 , —NHR 6 SO 2 R 8 , —OC(O)NR 6 R 7 , —N 3 , —OC(O)OR 7 , —CO 2 R 8 , —OC(O)R 6 , —NR 7 COR 6 , —N(COR 6 ) 2 , —NR 7 CONR 6 R 7 , —NR 7 CO 2 R 8 , —NR 6 R 7 , —CONR 6 R 7 , —CO 2 H, aryl, heteroaryl and heterocyclyl;

alternatively, R 3 is —OR 3a , —NR 3a R 3b , —NHR 3a , —SO n R 3a , —SO 2 NHR 3a , —SO 2 NR 3a R 3b , —COR 3a , —CONHR 3a , or —CONR 3a R 3b ;

R 3a and R 3b are independently selected from C 1 –C 10 alkyl, C 2 –C 10 alkenyl, C 2 –C 10 alkynyl, C 3 –C 8 cycloalkyl, C 4 –C 12 cycloalkylalkyl, C 2 –C 10 alkoxyalkyl, C 5 –C 10 cycloalkenyl, and C 6 –C 10 cycloalkenylalkyl;

wherein one carbon in any cycloalkyl may be replaced with O, S or NR 9 ; and

wherein each C 1 –C 10 alkyl, C 2 –C 10 alkenyl, C 2 –C 10 alkynyl, C 3 –C 8 cycloalkyl, C 4 –C 12 cycloalkylalkyl, C 2 –C 10 alkoxyalkyl, C 5 –C 10 cycloalkenyl, and C 6 –C 10 cycloalkenylalkyl is optionally substituted with 1 to 3 substituents independently selected at each occurrence from C 1 –C 6 alkyl, C 2 –C 6 alkenyl, C 2 –C 10 alkynyl, C 3 –C 6 cycloalkyl, halogen, C 1 –C 4 haloalkyl, cyano, —OR 7 , —SH, —S(O) n R 11 , —COR 6 , —CO 2 R 8 , —OC(O)R 6 , —NR 7 COR 6 , —N(COR 6 ) 2 , —NR 7 CONR 6 R 7 , —NR 7 CO 2 R 8 , —NR 6 R 7 , —NHR 6 SO 2 R 8 , —OC(O)NR 6 R 7 , —N 3 , —OC(O)OR 7 , —CONR 6 R 7 , —CO 2 H, aryl, heteroaryl and heterocyclyl;

R 4 is independently selected in each occurrence from —H, —OR 10 , —COR 9 , —CO 2 R 8 , —CONR 9 R 10 , —CN, —NR 9 R 10 , —S(O) n R 12 , —S(O) 2 NR 9 R 10 , —NO 2 , halogen, C 1 –C 6 alkyl, C 1 –C 4 haloalkyl, C 1 –C 6 haloalkoxy, C 3 –C 6 cycloalkyl, C 2 –C 6 alkenyl, C 2 –C 6 alkynyl, aryl and heteroaryl;

wherein C 1 –C 6 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 cycloalkyl, C 2 –C 6 alkenyl, and C 2 –C 6 alkynyl, are optionally substituted with —OR 10 , —COR 9 , —CO 2 R 8 , —CONR 9 R 10 , —CN, —NR 9 R 10 , —S(O) n R 12 , or halogen;

A 1 is CR 5 ;

A 2 is CR 5 ;

R 5 is independently selected at each occurrence from —H, C 1 –C 10 alkyl, C 1 –C 4 haloalkyl, C 1 –C 4 haloalkoxy, C 2 –C 10 alkenyl, C 2 –C 10 alkynyl, C 3 –C 6 cycloalkyl, C 4 –C 12 cycloalkylalkyl, —NO 2 , halogen, —CN, —NR 6 R 7 , —NR 6 COR 7 , —NR 6 CO 2 R 8 , —COR 6 —OR 7 , —CONR 6 R 7 , —CO(NOR 9 )R 11 , —CO 2 R 8 , —S(O) 2 NR 9 R 10 , and —S(O) n R 11 ;

wherein C 1 –C 10 alkyl, C 2 –C 10 alkenyl, C 2 –C 10 alkynyl, C 3 –C 6 cycloalkyl and C 4 –C 12 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from C 1 –C 4 alkyl, C 2 –C 4 alkenyl, C 2 –C 4 alkynyl, C 3 –C 6 cycloalkyl, C 4 –C 8 cycloalkylalkyl, C 1 –C 4 haloalkyl, —NO 2 , halogen, —CN, —NR 6 R 7 , —NR 6 COR 7 , NR 6 CO 2 R 8 , —COR 6 —OR 7 , —CONR 6 R 7 , —CO 2 R 8 , —CO(NOR 9 )R 7 , and —S(O) n R 11 ;

alternatively, two R 5 groups on adjacent atoms can form a 5–7 membered fused ring, partially saturated or unsaturated, optionally containing 1–2 —O— or —SO n — or 1–3 N heteroatoms provided the ring does not contain any S—S, O—O, S—O or N—S bonds;

said 5–7 membered fused ring optionally substituted with C 1 –C 4 alkyl, C 2 –C 6 alkenyl, C 2 –C 6 alkynyl, C 3 –C 6 cycloalkyl, C 4 –C 8 cycloalkylalkyl, C 1 –C 4 haloalkyl, —NO 2 , halogen, —CN, —NR 6 R 7 , NR 6 COR 7 , NR 6 CO 2 R 8 , —COR 6 —OR 7 , —CONR 6 R 7 , —CO 2 R 8 , —CO(NOR 9 )R 7 , or —S(O) n R 11 ;

R 6 and R 7 are independently at each occurrence H, C 1 –C 6 alkyl, C 1 –C 4 haloalkyl, C 2 –C 8 alkoxyalkyl, C 3 –C 6 cycloalkyl, C 4 –C 12 cycloalkylalkyl, C 5 –C 12 bis(alkoxy)alkyl, aryl, aryl(C 1 –C 4 alkyl)-, heteroaryl or heteroaryl(C 1 –C 4 alkyl);

alternatively NR 6 R 7 is piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine;

R 8 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 cycloalkyl, C 4 –C 12 cycloalkylalkyl, aryl, aryl(C 1 –C 4 alkyl)-, heteroaryl or heteroaryl(C 1 –C 4 alkyl);

R 9 and R 10 are independently at each occurrence selected from H, C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 alkenyl, C 3 –C 6 alkynyl, C 3 –C 6 cycloalkyl, C 2 –C 6 alkoxyalkyl, and C 4 –C 7 cycloalkylalkyl;

R 11 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 cycloalkyl, C 4 –C 12 cycloalkylalkyl, aryl, aryl(C 1 –C 4 alkyl)-, heteroaryl, heteroaryl(C 1 –C 4 alkyl), or —NR 6 R 7 ;

R 12 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 alkenyl, C 3 –C 6 alkynyl, C 3 –C 6 cycloalkyl, or C 4 –C 7 cycloalkylalkyl;

aryl is phenyl or naphthyl, each optionally substituted with 1 to 5 substituents independently selected at each occurrence from C 1 –C 6 alkyl, C 3 –C 6 cycloalkyl, C 4 –C 7 cycloalkylalkyl, C 2 –C 6 alkenyl, C 2 –C 6 alkynyl, halogen, C 1 –C 4 haloalkyl, cyano, —OR 30 , —SH, —S(O) n R 32 , —COR 32 , —CO 2 R 28 , —OC(O)R 32 , —NR 29 COR 29 , —N(COR 32 ) 2 , —NR 29 CONR 29 R 30 , —NR 29 CO 2 R 28 , —NR 29 R 30 , and —CONR 29 R 30 ;

heteroaryl is pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, or indazolyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C 1 –C 6 alkyl, C 3 –C 6 cycloalkyl, C 4 –C 7 cycloalkylalkyl, C 2 –C 6 alkenyl, C 2 –C 6 alkynyl, halogen, C 1 –C 4 haloalkyl, cyano, —OR 30 , —SH, —S(O) n R 32 , —COR 32 , —CO 2 R 28 , —OC(O)R 32 , —NR 29 COR 29 , —N(COR 32 ) 2 , —NR 29 CONR 29 R 30 , —NR 29 CO 2 R 28 , —NR 29 R 30 , and —CONR 29 R 30 ;

heterocyclyl is saturated or partially saturated heteroaryl, optionally substituted with 1 to 3 substituents independently selected at each occurrence from C 1 –C 6 alkyl, C 3 –C 6 cycloalkyl, C 4 –C 7 cycloalkylalkyl, C 2 –C 6 alkenyl, C 2 –C 6 alkynyl, halogen, C 1 –C 4 haloalkyl, cyano, —OR 30 , SH, —S(O) n R 32 , —COR 32 , —CO 2 R 32 , —OC(O)R 32 , —NR 29 COR 29 , —N(COR 32 ) 2 , —NR 29 CONR 29 R 30 , —NR 29 CO 2 R 32 , —NR 29 R 30 , and —CONR 29 R 30 ;

R 28 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 cycloalkyl, C 4 –C 12 cycloalkylalkyl, phenyl, or phenyl(C 1 –C 4 alkyl)-;

R 29 and R 30 are independently at each occurrence selected from H, C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 alkenyl, C 3 –C 6 alkynyl, C 3 –C 6 cycloalkyl, C 2 –C 6 alkoxyalkyl, and C 4 –C 7 cycloalkylalkyl;

R 32 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 alkenyl, C 3 –C 6 alkynyl, C 3 –C 6 cycloalkyl, or C 4 –C 7 cycloalkylalkyl; and

n is 0, 1, or 2;

with the proviso that when the compound is of Formula II, X is N, W is (—H, —H), Y is CH 2 , A 1 is CH, A 2 is CH, R 4 is H, R 5 is H, and R 1 is OR 10 , then

when R 10 is Me and R 2 is CHO, B is other than OMe, and

when R 10 is C 4 –C 6 alkynyl and R 2 is H, B is other than Me; and

with the proviso that when the compound is of Formula II, X is N, W is —H, Y is CH═,

R 1 is Me, A 1 is CH, R 2 is H, R 4 is H, R 6 is H, and R 10 is H, then

when A 2 is CH, B is other than NHMe, and

when A 2 is COMe, B is other than NH 2 .

2. A compound of claim 1 of Formula (I):

or a pharmaceutically acceptable salt form thereof, wherein:

W is (—H, —H);

Y is —CH 2 —, —CH(CH 3 )—, or —C(CH 3 ) 2 —;

R 1 is H, halogen, —CN, C 1 –C 2 haloalkyl, —OR 10 , C 1 –C 4 alkyl, C 2 –C 4 alkenyl, C 2 –C 4 alkynyl, C 3 –C 4 cycloalkyl, and C 4 –C 6 cycloalkylalkyl;

wherein each C 1 –C 4 alkyl, C 2 –C 4 alkenyl, or C 2 –C 4 alkynyl, is each optionally substituted with F, Cl, Br, CN, —OH, —CH 3 , —OCH 3 , —CF 3 , or —OCF 3 ;

R 2a is H, F, Cl, Br, —CN, —OH, —CH 3 , —OCH 3 , —CF 3 , or —OCF 3 ;

R 3 is C 1 –C 8 alkyl, C 3 –C 8 alkenyl, C 3 –C 8 alkynyl, C 3 –C 6 cycloalkyl, C 4 –C 10 cycloalkylalkyl, C 2 –C 10 alkoxyalkyl, C 5 –C 6 cycloalkenyl, or C 6 –C 10 cycloalkenylalkyl;

wherein each C 1 –C 8 alkyl, C 3 –C 8 alkenyl, C 3 –C 8 alkynyl, C 3 –C 6 cycloalkyl, C 4 –C 10 cycloalkylalkyl, C 2 –C 10 alkoxyalkyl, C 5 –C 6 cycloalkenyl, or C 6 –C 10 cycloalkenylalkyl is optionally substituted with 1, 2 or 3 substituents independently selected at each occurrence from methyl, ethyl, cyclopropyl, cyclobutyl, F, Cl, Br, —CF 3 , cyano, —OR 7 , —S(O) n R 11 , —COR 6 , —NHR 6 SO 2 R 8 , —OC(O)NR 6 R 7 , —N 3 , —OC(O)OR 7 , —CO 2 R 8 , —OC(O)R 6 , —NR 7 COR 6 , —N(COR 6 ) 2 , —NR 7 CONR 6 R 7 , —NR 7 CO 2 R 8 , —NR 6 R 7 , —CONR 6 R 7 , and —CO 2 H;

alternatively, R 3 is —S(O)R 3a , —S(O) 2 R 3a , —COR 3a , —CONHR 3a , or —CONR 3a R 3b ;

R 3a and R 3b are independently selected from C 1 –C 8 alkyl, C 3 –C 8 alkenyl, C 3 –C 8 alkynyl, C 3 –C 6 cycloalkyl, C 4 –C 10 cycloalkylalkyl, C 2 –C 10 alkoxyalkyl, C 5 –C 6 cycloalkenyl, or C 6 –C 10 cycloalkenylalkyl;

R 4 is —H, —OR 10 , —COR 9 , —CO 2 R 8 , —CONR 9 R 10 , —CN, —NR 9 R 10 , —S(O) n R 12 , —S(O) 2 NR 9 R 10 , —NO 2 , halogen, C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 1 –C 4 haloalkoxy, C 3 –C 6 cycloalkyl, C 2 –C 4 alkenyl, or C 2 –C 4 alkynyl;

wherein C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 cycloalkyl, C 2 –C 4 alkenyl, or C 2 –C 4 alkynyl, are optionally substituted with —OR 10 , —COR 9 , —CO 2 R 8 , —CONR 9 R 10 , —CN, —NR 9 R 10 , —S(O) n R 12 , or halogen;

A 1 is CR 5 ;

A 2 is CR 5 ;

R 5 is independently selected at each occurrence from —H, C 1 –C 6 alkyl, C 1 –C 4 haloalkyl, C 1 –C 4 haloalkoxy, C 2 –C 6 alkenyl, C 2 –C 6 alkynyl, C 3 –C 6 cycloalkyl, C 4 –C 10 cycloalkylalkyl, —NO 2 , halogen, —CN, —NR 6 R 7 , —NR 6 COR 7 , —NR 6 CO 2 R 8 , —COR 6 —OR 7 , —CONR 6 R 7 , —CO(NOR 9 )R 11 , —CO 2 R 8 , —S(O) 2 NR 9 R 10 , and —S(O) n R 11 ;

wherein C 1 –C 6 alkyl, C 2 –C 6 alkenyl, C 2 –C 6 alkynyl, C 3 –C 6 cycloalkyl and C 4 –C 10 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from C 1 –C 4 alkyl, C 2 –C 4 alkenyl, C 2 –C 4 alkynyl, C 3 –C 6 cycloalkyl, C 4 –C 8 cycloalkylalkyl, C 1 –C 4 haloalkyl, —NO 2 , halogen, —CN, —NR 6 R 7 , —NR 6 COR 7 , NR 6 CO 2 R 8 , —COR 6 —OR 7 , —CONR 6 R 7 , —CO 2 R 8 , —CO(NOR 9 )R 7 , and —S(O) n R 11 ;

R 6 and R 7 are independently at each occurrence H, methyl, ethyl, propyl, or butyl;

R 8 is independently at each occurrence methyl, ethyl, propyl, or butyl;

R 9 and R 10 are independently at each occurrence selected from H, methyl, ethyl, propyl, or butyl;

R 11 is independently at each occurrence H, methyl, ethyl, propyl, butyl, or —NR 6 R 7 ;

R 12 is independently at each occurrence methyl, ethyl, propyl, or butyl; and

n is 0, 1, or 2.

3. A compound of claim 2 of Formula (I-b):

or a pharmaceutically acceptable salt form thereof, wherein:

R 1 is H, halogen, —CN, C 1 –C 2 haloalkyl, —OR 10 , or C 1 –C 3 alkyl;

R 3 is C 1 –C 6 alkyl, C 3 –C 6 alkenyl, C 3 –C 6 alkynyl, C 3 –C 6 cycloalkyl, C 4 –C 7 cycloalkylalkyl, C 2 –C 6 alkoxyalkyl, C 5 –C 6 cycloalkenyl, or C 6 –C 7 cycloalkenylalkyl;

wherein each C 1 –C 6 alkyl, C 3 –C 6 alkenyl, C 3 –C 6 alkynyl, C 3 –C 6 cycloalkyl, C 4 –C 7 cycloalkylalkyl, C 2 –C 6 alkoxyalkyl, C 5 –C 6 cycloalkenyl, or C 6 –C 7 cycloalkenylalkyl is optionally substituted with 1 or 2 substituents independently selected at each occurrence from methyl, ethyl, methoxy, ethoxy, methyl-S—, ethyl-S—, cyclopropyl, cyclobutyl, F, Cl, —CF 3 and —OCF 3 ;

R 4 is —H, —OR 10 , —CN, —NR 9 R 10 , —S(O) 2 NR 9 R 10 , —NO 2 , halogen, C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 1 –C 4 haloalkoxy, C 2 –C 4 alkenyl, C 2 –C 4 alkynyl, —SR 12 , —S(O)R 12 , or —S(O) 2 R 12 ;

R 5 is independently at each occurrence —H, C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 1 –C 4 haloalkoxy, C 2 –C 4 alkenyl, C 2 –C 4 alkynyl, C 3 –C 4 cycloalkyl, C 4 –C 5 cycloalkylalkyl, —NO 2 , halogen, —CN, —NR 6 R 7 , —NR 6 COR 7 , —NR 6 CO 2 R 8 , —COR 6 —OR 7 , —CONR 6 R 7 , —S(O) 2 NR 9 R 10 , —CO 2 R 8 , —SCH 3 , —SCH 2 CH 3 , —S(O)R 11 , or —S(O) 2 R 11 ;

R 6 and R 7 are independently at each occurrence H, methyl, or ethyl;

R 8 is independently at each occurrence methyl or ethyl;

R 9 and R 10 are independently at each occurrence selected from H, methyl, or ethyl;

R 11 is independently at each occurrence methyl, ethyl, or —NR 6 R 7 ; and

R 12 is independently at each occurrence methyl or ethyl.

4. A compound of claim 3 of Formula (I-c):

or a pharmaceutically acceptable salt form thereof, wherein:

R 1 is H, F, Cl, Br, —CN, methyl, ethyl, methoxy, or C 1 –C 2 haloalkyl;

R 3 is C 1 –C 6 alkyl optionally substituted with 1 or 2 substituents independently selected at each occurrence from methyl, ethyl, methoxy, ethoxy, methyl-S—, ethyl-S—, cyclopropyl, cyclobutyl, and —CF 3 ;

R 4 is —H, F, Cl, Br, —CN, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C 1 –C 2 haloalkyl, or C 1 –C 2 haloalkoxy; and

R 5 is independently at each occurrence —H, F, Cl, Br, —CN, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C 1 –C 2 haloalkyl, or C 1 –C 2 haloalkoxy.

5. A compound of claim 4 of Formula (I-c):

or a pharmaceutically acceptable salt form thereof, wherein:

R 1 is H, F, Cl, Br, methyl, ethyl, —CN, or —CF 3 ;

R 3 is butyl-, pentyl-, hexyl-, heptyl-, methoxy-ethyl-, methoxy-propyl-, methoxy-butyl-, methoxy-pentyl-, methoxy-hexyl-, methylthio-ethyl-, methylthio-propyl-, methylthio-butyl-, methylthio-pentyl-, methylthio-hexyl-, 1-cyclopropyl-propyl-, 1-cyclopropyl-butyl-, 1-cyclopropyl-pentyl-, 1-cyclobutyl-propyl-, 1-cyclobutyl-butyl-, 1-cyclobutyl-pentyl, 1-cyclopropyl-1-(CF 3 )-methyl-, 1-cyclopropyl-2-(CF 3 )-ethyl-, 1-cyclopropyl-3-(CF 3 )-propyl-, 1-cyclobutyl-1-(CF 3 )-methyl-, 1-cyclobutyl-2-(CF 3 )-ethyl-, or 1-cyclobutyl-3-(CF 3 )-propyl-;

R 4 is H, methyl-, ethyl-, methoxy-, ethoxy-, isopropoxy-, n-propoxy-, F, Cl, Br, —CF 3 , —OCF 3 , —OCHF 2 , —CN; and

R 5 is independently at each occurrence, —H, methyl, ethyl, methoxy, ethoxy, F, Cl, Br, or —CF 3 .

6. A compound of claim 2 selected from:

5-Chloro-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-1-(1-ethylpropyl)-2(1H)-pyrazinone;

5-Chloro-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-1-(1-ethyl-3-methoxypropyl)-2(1H)-pyrazinone;

5-Chloro-1-(1-ethylpropyl)-3-(5-methoxy-7-methyl-2,3-dihydro-1H-indol-1-yl)-2(1H)-pyrazinone;

3-(7-Bromo-5-methoxy-2,3-dihydro-1H-indol-1-yl)-5-chloro-1-(1-ethylpropyl)-2(1H)-pyrazinone;

3-(5,7-Dichloro-2,3-dihydro-1H-indol-1-yl)-1-(1-ethylpropyl)-5-methyl-2(1H)-pyrazinone;

3-(5-Methoxy-7-methyl-2,3-dihydro-1H-indol-1-yl)-1-(1-ethylpropyl)-5-methyl-2(1H)-pyrazinone;

5-Chloro-3-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-(1-methylpropyl)-2(1H)-pyrazinone;

-3-(7-Bromo-5-methoxy-2,3-dihydro-1H-indol-1-yl)-5-chloro-1-(1-methylpropyl)-2(1H)-pyrazinone;

5-Chloro-3-(5-methoxy-7-methyl-2,3-dihydro-1H-indol-1-yl)-1-(1-methylpropyl)-2(1H)-pyrazinone;

5-Chloro-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-1-(1-methylpropyl)-2(1H)-pyrazinone;

5-Bromo-3-(7-bromo-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-(1-ethylpropyl)-2(1H)-pyrazinone;

5-Bromo-1-(1-ethylpropyl)-3-(5-methoxy-7-methyl-2,3-dihydro-1H-indol-1-yl)-2(1H)-pyrazinone;

5-Bromo-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-1-(1-ethylpropyl)-2(1H)-pyrazinone;

5-Chloro-3-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-[(1R)-1-cyclopropylpropyl]-2(1H)-pyrazinone;

3-(7-Bromo-5-methoxy-2,3-dihydro-1H-indol-1-yl)-5-chloro-1-[(1R)-1-cyclopropylpropyl]-2(1H)-pyrazinone;

5-Chloro-1-[(1R)-1-cyclopropylpropyl]-3-(5-methoxy-7-methyl-2,3-dihydro-1H-indol-1-yl)-2(1H)-pyrazinone;

5-Chloro-1-[(1R)-1-cyclopropylpropyl]-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-2(1H)-pyrazinone;

5-Chloro-1-[(1R)-1-cyclopropylpropyl]-3-(5,7-dibromo-2,3-dihydro-1H-indol-1-yl)-2(1H)-pyrazinone;

5-Chloro-3-(7-chloro-6-fluoro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-[(1R)-1-cyclopropylpropyl]-2(1H)-pyrazinone;

5-Chloro-3-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-[(1S)-1-cyclopropylpropyl]-2(1H)-pyrazinone;

3-(7-Bromo-5-methoxy-2,3-dihydro-1H-indol-1-yl)-5-chloro-1-[(1S)-1-cyclopropylpropyl]-2(1H)-pyrazinone;

5-Chloro-1-[(1S)-1-cyclopropylpropyl]-3-(5-methoxy-7-methyl-2,3-dihydro-1H-indol-1-yl)-2(1H)-pyrazinone;

5-Chloro-1-[(1S)-1-cyclopropylpropyl]-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-2(1H)-pyrazinone;

5-Chloro-1-[(1S)-1-cyclopropylpropyl]-3-(5,7-dibromo-2,3-dihydro-1H-indol-1-yl)-2(1H)-pyrazinone;

5-Chloro-3-(7-chloro-6-fluoro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-[(1S)-1-cyclopropylpropyl]-2(1H)-pyrazinone;

5-Chloro-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-1-[(1R)-2-methoxy-1-methylethyl]-2(1H)-pyrazinone;

5-Chloro-3-(5,7-dibromo-2,3-dihydro-1H-indol-1-yl)-1-[(1R)-2-methoxy-1-methylethyl]-2(1H)-pyrazinone;

5-Chloro-3-(7-chloro-6-fluoro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-[1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

3-(7-Bromo-5-methoxy-2,3-dihydro-1H-indol-1-yl)-5-chloro-1-[(1R)-1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

5-Chloro-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-1-[(1R)-1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

5-Bromo-3-(7-bromo-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-[(1R)-1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

5-Bromo-3-(5-methoxy-7-methyl-2,3-dihydro-1H-indol-1-yl)-1-[(1R)-1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

5-Bromo-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-1-[(1R)-1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

5-Bromo-3-(7-chloro-6-fluoro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-[(1R)-1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

3-(7-Bromo-5-methoxy-2,3-dihydro-1H-indol-1-yl)-5-chloro-1-[(1S)-1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

5-Chloro-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-1-[(1S)-1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

5-Bromo-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-1-[(1S)-1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

5-Chloro-3-(5-methoxy-7-methyl-2,3-dihydro-1H-indol-1-yl)-1-[2-methyl-1-(1-methylethyl)propyl]-2(1H)-pyrazinone;

3-(7-Bromo-5-methoxy-2,3-dihydro-1H-indol-1-yl)-5-chloro-1-[2-(methylthio)ethyl]-2(1H)-pyrazinone;

5-Chloro-3-(5-methoxy-7-methyl-2,3-dihydro-1H-indol-1-yl)-1-[2-(methylthio)ethyl]-2(1H)-pyrazinone;

5-Chloro-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-1-[2-(methylthio)ethyl]-2(1H)-pyrazinone;

5-Chloro-3-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-(1-ethylpropyl)-6-methyl-2(1H)-pyrazinone;

5-Chloro-3-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-(1-cyclobutylpropyl)-6-methyl-2(1H)-pyrazinone;

3-(5-Bromo-7-chloro-2,3-dihydro-1H-indol-1-yl)-5-chloro-1-methylpropyl-2(1H)-pyrazinone;

3-(5,7-Dichloro-2,3-dihydro-1H-indol-1-yl)-5-ethyl-1-(1-ethylpropyl)-2(1H)-pyrazinone;

3-(5-Bromo-7-chloro-2,3-dihydro-1H-indol-1-yl)-5-chloro-1-(1-ethylpropyl)-2(1H)-pyrazinone;

6-(5,7-Dichloro-2,3-dihydro-1H-indol-1-yl)-4-(1-ethylpropyl)-4,5-dihydro-5-oxo-2-pyrazinecarbonitrile;

3-(5-Bromo-7-chloro-2,3-dihydro-1H-indol-1-yl)-5-chloro-1-[(1R)-1-cyclopropylpropyl]-2(1H)-pyrazinone;

3-(5-Bromo-7-chloro-2,3-dihydro-1H-indol-1-yl)-5-chloro-1-[(1S)-1-cyclopropylpropyl]-2(1H)-pyrazinone;

5-Chloro-3-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-[(1R)-1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

5-Chloro-3-(5-methoxy-7-methyl-2,3-dihydro-1H-indol-1-yl)-1-[(1R)-1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

1-[6-Chloro-4-[(1R)-1-(methoxymethyl)propyl]-3,4-dihydro-3-oxopyrazinyl]-5-methoxy-2,3-dihydro-1H-indole-7-carbonitrile;

5-Bromo-3-(5-bromo-7-chloro-2,3-dihydro-1H-indol-1-yl)-1-[(1R)-1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

3-(5-Bromo-7-chloro-2,3-dihydro-1H-indol-1-yl)-5-chloro-1-[(1S)-1-(methoxymethyl)propyl]-2(1H)-pyrazinone; and

5-Chloro-3-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-(1-cyclobutylpropyl)-2(1H)-pyrazinone.

7. A compound of claim 1 of Formula (I-a) or (II):

or a pharmaceutically acceptable salt form thereof, wherein:

X is N or CR 1 ;

provided that when X is N, R 1 can not be either —NR 9 R 10 or —NR 9 COR 9 ;

W is O, S, H or (—H, —H);

Y is CO, CH 2 , or CH;

B is R 3 , NHR 3 , NR 3 R 1 , OR 3 , or SO n R 3 ;

R 2 is H, halogen, CN, C 1 –C 4 haloalkyl, —NR 9 R 10 , NR 9 COR 9 , —COR 10 , —OR 10 , SH, —S(O) n R 12 , C 1 –C 4 alkyl, C 3 –C 6 cycloalkyl, or C 4 –C 8 cycloalkylalkyl;

wherein one carbon in any cycloalkyl ring may be replaced with O, S or NR 9 ; and

C 3 –C 6 cycloalkyl, halogen, C 1 –C 4 haloalkyl, cyano, —OR 7 , SH, —S(O) n R 11 , —COR 6 , —NHR 6 SO 2 R 8 , —OC(O)NR 6 R 7 , —N 3 , —OC(O)OR 7 , —CO 2 R 8 , —OC(O)R 6 , —NR 7 COR 6 , —N(COR 6 ) 2 , —NR 7 CONR 6 R 7 , —NR 7 CO 2 R 8 , —NR 6 R 7 , —CONR 6 R 7 , —CO 2 H, aryl, heteroaryl and heterocyclyl;

alternatively, R 3 is —OR 3a , —NR 3a R 3b , —NHR 3a , —SO n R 3a , —SO 2 NHR 3a , —SO 2 NR 3a R 3b , —COR 3a , —CONHR 3a , or —CONR 3a R 3b ;

wherein one carbon in any cycloalkyl may be replaced with O, S or NR 9 ; and

R 4 is independently selected in each occurrence from —H, —OR 10 , —COR 9 , —CO 2 R 8 , —CONR 9 R 10 , —CN, —NR 9 R 10 , —S(O) n R 12 , halogen, C 1 –C 6 alkyl, C 1 –C 4 haloalkyl, C 1 –C 6 haloalkoxy, C 3 –C 6 cycloalkyl, C 2 –C 6 alkenyl, C 2 –C 6 alkynyl, aryl and heteroaryl;

A 1 is CR 5 ;

A 2 is CR 5 ;

R 5 is independently at each occurrence —H, C 1 –C 10 alkyl, C 1 –C 4 haloalkyl, C 1 –C 4 haloalkoxy, C 2 –C 10 alkenyl, C 2 –C 10 alkynyl, C 3 –C 6 cycloalkyl, C 4 –C 12 cycloalkylalkyl, —NO 2 , halogen, —CN, —NR 6 R 7 , —NR 6 COR 7 , —NR 6 CO 2 R 8 , —COR 6 —OR 7 , —CONR 6 R 7 , —CO(NOR 9 )R 11 , —CO 2 R 8 , or —S(O) n R 11 ;

alternatively NR 6 R 7 is piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine;

R 12 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 alkenyl, C 3 –C 6 alkynyl, C 3 –C 6 cycloalkyl, or C 4 –C 7 cycloalkylalkyl;

R 28 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 cycloalkyl, C 4 –C 12 cycloalkylalkyl, phenyl, or phenyl(C 1 –C 4 alkyl)-;

R 32 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 alkenyl, C 3 –C 6 alkynyl, C 3 –C 6 cycloalkyl, or C 4 –C 7 cycloalkylalkyl; and

n is 0, 1, or 2.

8. A compound of claim 7 of Formula (I-a):

wherein:

W is (—H, —H);

Y is CH 2 ;

R 2 is H, halogen, CN, C 1 –C 4 haloalkyl, —NR 9 R 10 , NR 9 COR 9 , —COR 10 , —OR 10 , SH, —S(O) n R 12 , C 1 –C 4 alkyl, C 3 –C 6 cycloalkyl, or C 4 –C 7 cycloalkylalkyl;

wherein each C 1 –C 4 alkyl, C 3 –C 6 cycloalkyl, or C 4 –C 7 cycloalkylalkyl is optionally substituted with halogen, —CN, C 1 –C 4 haloalkyl, —NR 9 R 10 , —NR 9 COR 9 , —COR 10 , —OR 10 , SH or —S(O) n R 12 ;

wherein one carbon in any cycloalkyl ring may be replaced with O, S or NR 9 ; and

alternatively, R 3 is —OR 3a , —NR 3a R 3b , —NHR 3a , SO n R 3a , —SO 2 NHR 3a , —SO 2 NR 3a R 3b , —COR 3a , —CONHR 3a , or —CONR 3a R 3b ;

wherein one carbon in any cycloalkyl may be replaced with O, S or NR 9 ; and

A 1 is CH;

A 2 is CH;

alternatively NR 6 R 7 is piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine;

R 12 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 alkenyl, C 3 –C 6 alkynyl, C 3 –C 6 cycloalkyl, or C 4 –C 7 cycloalkylalkyl;

C 3 –C 6 cycloalkyl, C 4 –C 7 cycloalkylalkyl, C 2 –C 6 alkenyl, C 2 –C 6 alkynyl, halogen, C 1 –C 4 haloalkyl, cyano, —OR 30 , —SH, —S(O) n R 32 , —COR 32 , —CO 2 R 28 , —OC(O)R 32 , —NR 29 COR 29 , —N(COR 32 ) 2 , —NR 29 CONR 29 R 30 , —NR 29 CO 2 R 28 , —NR 29 R 30 , and —CONR 29 R 30 ;

R 28 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 cycloalkyl, C 4 –C 12 cycloalkylalkyl, phenyl, or phenyl(C 1 –C 4 alkyl)-;

R 32 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 alkenyl, C 3 –C 6 alkynyl, C 3 –C 6 cycloalkyl, or C 4 –C 7 cycloalkylalkyl; and

n is 0, 1, or 2.

9. A compound of claim 8 of Formula (I-a) wherein:

W is (—H, —H);

Y is CH 2 ;

R 1 is a halogen;

R 3 is C 1 –C 10 alkyl, C 3 –C 8 cycloalkyl, C 4 –C 12 cycloalkylalkyl, or C 2 –C 10 alkoxyalkyl;

wherein one carbon in any cycloalkyl ring may be replaced with O, S or NR 9 ;

R 4 and R 5 are independently selected at each occurrence from —OR 10 , halogen, C 1 –C 6 alkyl, and C 1 –C 6 haloalkoxy;

A 1 is CH;

A 2 is CH;

10. A compound of claim 9 of Formula (I-a) wherein:

W is (—H, —H);

Y is CH 2 ;

R 1 is a halogen;

R 3 is C 1 –C 10 alkyl, C 3 –C 8 cycloalkyl, C 4 –C 12 cycloalkylalkyl, or C 2 –C 10 alkoxyalkyl;

R 4 and R 5 are independently selected in each occurrence from —OR 10 , halogen, C 1 –C 6 alkyl, and C 1 –C 6 haloalkoxy;

A 1 is CH;

A 2 is CH; and

R 10 is independently at each occurrence selected from C 1 –C 4 alkyl.

11. A compound of claim 10 selected from:

5-Chloro-1-(1-cyclopropylpropyl)-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-2(1H)-pyrazinone;

5-Chloro-3-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-1-[1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

5-Chloro-3-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-[1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

5-Chloro-3-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-(1-ethyl-3-methoxypropyl)-2(1H)-pyrazinone;

5-Chloro-3-(5-methoxy-7-methyl-2,3-dihydro-1H-indol-1-yl)-1-[1-(methoxymethyl)propyl]-2(1H)-pyrazinone;

5-Chloro-3-(7-bromo-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-[1-(methoxymethyl)propyl]-2(1H)-pyrazinone; and

5-Chloro-3-(7-bromo-5-methoxy-2,3-dihydro-1H-indol-1-yl)-1-(1-ethyl-3-methoxypropyl)-2(1H)-pyrazinone.

12. A compound of claim 7 of Formula (II)

wherein:

X is N;

W is (—H, —H);

Y is CH 2 ;

B is NHR 3 ;

R 2 is H, halogen, CN, C 1 –C 4 haloalkyl, —COR 10 , —OR 10 , SH, —S(O) n R 12 , C 1 –C 4 alkyl, C 3 –C 6 cycloalkyl, or C 4 –C 7 cycloalkylalkyl;

wherein one carbon in any cycloalkyl ring may be replaced with O, S or NR 9 ; and

A 1 are CH;

A 2 are CH;

alternatively NR 6 R 7 is piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine;

R 12 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 alkenyl, C 3 –C 6 alkynyl, C 3 –C 6 cycloalkyl, or C 4 –C 7 cycloalkylalkyl;

aryl is phenyl or naphthyl, each optionally substituted with 1 to 5 substituents independently selected at each occurrence from C 1 –C 6 alkyl, C 3 –C 6 cycloalkyl, C 4 –C 7 cycloalkylalkyl, C 2 –C 6 alkenyl, C 2 –C 6 alkynyl, halogen, C 1 –C 4 haloalkyl, cyano, —OR 30 , —SH, —S(O) n R 32 —COR 32 , —CO 2 R 28 , —OC(O)R 32 , —NR 29 COR 29 , —N(COR 32 ) 2 , —NR 29 CONR 29 R 30 , —NR 29 CO 2 R 28 , —NR 29 R 30 , and —CONR 29 R 30 ;

R 28 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 cycloalkyl, C 4 –C 12 cycloalkylalkyl, phenyl, or phenyl(C 1 –C 4 alkyl)-;

R 32 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 alkenyl, C 3 –C 6 alkynyl, C 3 –C 6 cycloalkyl, or C 4 –C 7 cycloalkylalkyl; and

n is 0, 1, or 2.

13. A compound of claim 12 wherein:

X is N;

W is (—H, —H);

Y is CH 2 ;

B is NHR 3 ;

R 1 is C 1 –C 6 alkyl;

R 2 is H, halogen, CN, or —COR 10 ;

R 4 and R 5 are independently selected in each occurrence —OR 10 , halogen, or C 1 –C 6 haloalkoxy;

A 1 and A 2 are CH; and

R 10 is H.

14. A compound of claim 13 selected from:

4-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-6-(1-ethylpropylamino)-2-methylpyrimidine;

5-chloro-4-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-6-(1-ethylpropylamino)-2-methylpyrimidine;

5-bromo-4-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-6-(1-ethylpropylamino)-2-methylpyrimidine;

4-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-6-(1-ethylpropylamino)-5-iodo-2-methylpyrimidine;

5-cyano-4-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-6-(1-ethylpropylamino)-2-methylpyrimidine;

4-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-6-(1-ethylpropylamino)-5-formyl-2-methylpyrimidine;

4-(5,7-dichloro-2,3-dihydro-1H-indol-1-yl)-6-(1-ethylpropylamino)-5-hydroxymethyl-2-methylpyrimidine;

4-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-6-(1-ethylpropylamino)-2-methylpyrimidine;

4-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-5-cyano-6-(1-ethylpropylamino)-2-methylpyrimidine;

4-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-6-(1-ethylpropylamino)-5-formyl-2-methylpyrimidine;

4-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-6-[1-(1-ethyl-3-methoxy)propylamino]-2-methylpyrimidine;

4-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-6-[1-(1-ethyl-3-methoxy)propylamino]-5-iodo-2-methylpyrimidine;

4-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-5-cyano-6-[1-(1-ethyl-3-methoxy)propylamino]-2-methylpyrimidine;

4-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-6-[1-(1-methoxymethyl)propylamino]-2-methylpyrimidine;

4-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-5-iodo-6-[1-(1-methoxymethyl)propylamino]-2-methylpyrimidine;

4-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-5-cyano-6-[1-(1-methoxymethyl)propylamino]-2-methylpyrimidine;

4-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-5-formyl-6-[1-(1-methoxymethyl)propylamino]-2-methylpyrimidine;

4-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-6-(1-methylbutylamino)-2-methylpyrimidine;

4-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-6-(1-methylpropylamino)-2-methylpyrimidine; and

4-(7-chloro-5-methoxy-2,3-dihydro-1H-indol-1-yl)-6-[1-(1-cyclobutyl)ethylamino)-2-methylpyrimidine.

15. A compound of claim 7 wherein:

X is CR 1 ;

W is (—H, —H);

Y is CH 2 ;

B is NHR 3 ;

R 2 is H, halogen, CN, C 1 –C 4 haloalkyl, —COR 10 , —OR 10 , SH, —S(O) n R 12 , C 1 –C 4 alkyl, C 3 –C 6 cycloalkyl, or C 4 –C 7 cycloalkylalkyl;

wherein each C 1 –C 4 alkyl, C 3 –C 6 cycloalkyl, or C 4 –C 7 cycloalkylalkyl is optionally substituted with halogen, —CN, C 1 –C 4 haloalkyl, —NR 9 R 1 , —NR 9 COR 9 , —COR 10 , —OR 10 , SH or —S(O) n R 12 ;

wherein one carbon in any cycloalkyl ring may be replaced with O, S or NR 9 ; and

A 1 are CH;

A 2 are CH;

alternatively NR 6 R 7 is piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine;

R 12 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 alkenyl, C 3 –C 6 alkynyl, C 3 –C 6 cycloalkyl, or C 4 –C 7 cycloalkylalkyl;

R 28 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 cycloalkyl, C 4 –C 12 cycloalkylalkyl, phenyl, or phenyl(C 1 –C 4 alkyl)-;

R 32 is independently at each occurrence C 1 –C 4 alkyl, C 1 –C 4 haloalkyl, C 3 –C 6 alkenyl, C 3 –C 6 alkynyl, C 3 –C 6 cycloalkyl, or C 4 –C 7 cycloalkylalkyl; and

n is 0, 1, or 2.

16. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.