Tricyclic compounds useful as inhibitors of kinases

1. The compound of Formula II

wherein R 3 is:

(a) hydrogen,

(b) halo,

(c) CF 3 ,

(d) C 1-6 alkyl, which is optionally substituted with one or more groups selected from C 1-6 alkyl, halo or R 10 ;

(e) C 3-6 cycloalkyl, which is optionally substituted with one or more groups selected from C 1-6 alkyl, halo or R 10 ;

(f) Aryl, which is optionally substituted with one or more groups selected from C 1-6 alkyl, halo or R 10 ;

(g) C 4-10 heterocyclyl, which is optionally substituted on either the carbon or the heteroatom with C 1-6 alkyl, halo or R 10 ;

(h) L-A-R 10 ,

(i) —OC 1-6 alkyl, which is optionally substituted with one or more groups selected from C 1-6 alkyl, halo or R 10 ;

(j) —OAryl, which is optionally substituted with one or more groups selected from C 1-6 alkyl, halo or R 10 ;

R 4 is:

(a) hydrogen,

(b) C 1-6 alkyl, which is optionally substituted with aryl or heteroaryl,

(c) C 3-6 cycloalkyl, which is optionally substituted with aryl or heteroaryl,

(d) Aryl, which is optionally substituted with one to five halo or R 10 ; or

(e) Heteroaryl (wherein the heteroaryl has 5 or 6 members in which 1, 2 3 or 4 of the atoms is a heteroatom selected from N, S and O), which is optionally substituted with one to five halo or R 10 ;

R 10 is hydrogen or is selected from the group consisting of:

(a) hydrogen;

(b) CO 2 R 11 ;

(c) C(O)R 11 ;

(d) NHR 11 ;

(e) NR 11 R 12 ;

(f) NHS(O) 2 R 11 ;

(g) NHC(O)R 11 ;

(h) NHC(O)OR 11 ;

(i) NH—C═(NH)NH 2 ;

(j) NHC(O)NH 2 ;

(k) NHC(O)NHR 11 ;

(l) NHC(O)NR 11 R 12 ;

(m) N C 3-6 cycloalkyl;

(n) C(O)NHR 11 ;

(o) C(O)NR 11 R 12 ;

(p) SO 2 NHR 11 ;

(q) SO 2 NHC(O)R 12 ;

R 11 is selected from the group consisting of:

(a) hydrogen;

(b) C 3-6 cycloalkyl, which is optionally substituted with aryl, heteroaryl, or one to five halo;

(c) C 1-6 alkyl, which is optionally substituted with aryl, heteroaryl, or one to five halo;

(d) Aryl, which is optionally substituted with one to five halo; or

(e) Heteroaryl (wherein the heteroaryl has 5 or 6 members in which 1, 2 3 or 4 of the atoms is a heteroatom selected from N, S and O), which is optionally substituted with one to five halo;

R 12 is selected from the group consisting of:

(a) hydrogen,

(b) C 1-6 alkyl, which is optionally substituted with aryl, heteroaryl or one to five halo;

(c) C 3-6 cycloalkyl, which is optionally substituted with aryl, heteroaryl or one to five halo;

(d) Aryl, which is optionally substituted with one to five halo;

(e) Heteroaryl (wherein the heteroaryl has 5 or 6 members in which 1, 2 3 or 4 of the atoms is a heteroatom selected from N, S and O), which is optionally substituted with one to five halo;

A is absent or is selected from the group consisting of: a aryl or Heteroaryl, wherein the heteroaryl is a ring of 5 or 6 atoms a monocyclic ring of 5 or 6 atoms or a bicyclic ring of 9 or 10 atoms in which 1, 2, 3 or 4 of the atoms is a heteroatom selected from N, S and O, wherein the aryl or heteroaryl is optionally substituted with one or more substituents selected from halo, C 1-3 alkyl, —C(O)OH, CF 3 , —SO 2 C 1-3 alkyl, SO 2 NC 1-3 alkyl, SO 2 NHC(O)—C 1-3 alkyl and N(CH 3 ) 2 ;

L is absent or is selected from the group consisting of: —(CH 2 ) k —W—, —W—(CH 2 ) k —, —C≡C—, —C 1-6 alkyl-, —C 3-6 cycloalkyl-, —C 2-5 alkene-, wherein the alkene is optionally substituted with one or more substituent group selected from C 1-6 alkyl and C 1-6 cycloalkyl;

X is selected from the group consisting of: NH and NC 1-6 alkyl;

D is selected from CH;

W is selected from the group consisting of: O, NH, NC 1-6 alkyl and S(O) m , with the proviso that when W is O, S(O) m , NH or NC 1-6 alkyl and simultaneously A is absent then R 10 is CO 2 R 11 , COR 11 , CONHR 11 or CONR 11 R 12 ;

U is CH;

V is CH;

Y is CH;

Z is CH;

k=0, 1, 2, 3, 4 or 5;

m=0, 1 or 2;

n=0, 1, 2 or 3;

or a pharmaceutically acceptable salt or stereoisomer thereof.

2. The compound selected from:

1-Amino-7-(trifluoromethyl)-5H-pyrido[4,3-b]indole-4-carboxamide;

1-Amino-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

8-Fluoro-1-(methylamino)-5H-pyrido[4,3-b]indole-4-carboxamide;

1-(Butylamino)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

8-Fluoro-1-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-pyrrolidin-1-yl-5H-pyrido[4,3-b]indole-4-carboxamide;

1-(ethylamino)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(propylamino)-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-piperidin-1-yl-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-morpholin-4-yl-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(methylamino)-5H-pyrido[4,3-b]indole-4-carboxamide;

1-(cyclohexylamino)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

1-(benzylamino)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(isobutylamino)-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(isopropylamino)-5H-pyrido[4,3-b]indole-4-carboxamide;

1-[(cyclohexylmethyl)amino]-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

1-(butylamino)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(pentylamino)-5H-pyrido[4,3-b]indole-4-carboxamide;

1-(cyclobutylamino)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

1-(cyclopentylamino)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

1-(cycloheptylamino)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

1-(cyclooctylamino)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-[(4-methylcyclohexyl)amino]-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-[(2-hydroxycyclohexyl)amino]-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-[(2-methylcyclohexyl)amino]-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-[(trans-4-hydroxycyclohexyl)amino]-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(tetrahydro-2H-pyran-4-ylamino)-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(heptylamino)-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-[(1,2,2-trimethylpropyl)amino]-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(hexylamino)-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(octylamino)-5H-pyrido[4,3-b]indole-4-carboxamide;

1-(2,2-dimethylmorpholin-4-yl)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

1-(3,3-difluoropyrrolidin-1-yl)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

1-(3,3-difluoropiperidin-1-yl)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(4-hydroxypiperidin-1-yl)-5H-pyrido[4,3-b]indole-4-carboxamide;

Ethyl-4-{[4-(aminocarbonyl)-8-fluoro-5H-pyrido[4,3-b]indol-1-yl]amino}piperidine-1-carboxylate;

1-[(1-benzylpiperidin-4-yl)amino]-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-[3-(hydroxymethyl)piperidin-1-yl]-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(4-phenyl-3,6-dihydropyridin-1(2H)-yl)-5H-pyrido[4,3-b]indole-4-carboxamide;

1-(4-benzyl-4-hydroxypiperidin-1-yl)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

1-(4-benzyl-3,6-dihydropyridin-1(2H)-yl)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

1-(4-benzylidenepiperidin-1-yl)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(4-phenylpiperidin-1-yl)-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(3-hydroxypiperidin-1-yl)-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(2-phenylpiperidin-1-yl)-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-{[(1S,2R)-2-(methoxymethyl)cyclopentyl]amino}-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-{[(1R)-1,2,2-trimethylpropyl]amino}-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-{[(15)-1,2,2-trimethylpropyl]amino}-5H-pyrido[4,3-b]indole-4-carboxamide;

N-[4-(aminocarbonyl)-8-fluoro-5H-pyrido[4,3-b]indol-1-yl]-3-methyl-D-valyl-N,3-dimethylvalinamide;

N-[4-(aminocarbonyl)-8-fluoro-5H-pyrido[4,3-b]indol-1-yl]-3-methyl-L-valyl-N,3-dimethylvalinamide;

1-(bicyclo[2.2.1]hept-2-ylamino)-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

1-{[(1R)-1-cyclohexylethyl]amino}-8-fluoro-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(3-phenylpiperidin-1-yl)-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(3-phenylpiperidin-1-yl)-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-[(1-hydroxypropyl)amino]-5H-pyrido[4,3-b]indole-4-carboxamide;

8-fluoro-1-(1′H,3H-spiro[2-benzofuran-1,4′-piperidin]-1′-yl)-5H-pyrido[4,3-b]indole-4-carboxamide;

1-Amino-5H-pyrido[4,3-b]indole-4-carboxamide;

1-Amino-8-bromo-5H-pyrido[4,3-b]indole-4-carboxamide;

1-Amino-6-chloro-5H-pyrido[4,3-b]indole-4-carboxamide;

1-Amino-5-methyl-7-(trifluoromethyl)-5H-pyrido[4,3-b]indole-4-carboxamide;

1-Amino-7-chloro-5H-pyrido[4,3-b]indole-4-carboxamide;

1-Amino-7-pyridin-3-yl-5-H-pyrido[4,3-b]indole-4-carboxamide;

or a pharmaceutically acceptable salt or stereoisomer thereof.

3. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier.