Inhibitors of Akt activity

1. A compound of the Formula B-1:

wherein:

a is 0 or 1; b is 0 or 1; m is 0, 1 or 2;

Q is selected from:

which may be optionally substituted with one or more substituents selected from: heterocyclyl, aryl, (C 3 -C 8 )cycloalkyl, O a (C 1 -C 6 )alkyl, OH, N(R b ) 2 , O—N(R b ) 2 , oxo and halogen, said heterocyclyl, aryl, cycloalkyl and alkyl optionally substituted with 1 to 3 substituents selected from (C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl-OH, O(C 1 -C 6 )alkyl oxo, OH, N(R b ) 2 and halogen;

R 1 is selected from: heterocyclyl, said heterocyclyl optionally substituted with R 10 ;

R 10 is selected from: H, (C═O) a O b C 1 -C 10 alkyl, (C═O) a O b aryl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, (C═O) a O b heterocyclyl, CO 2 H, halo, CN, OH, O b C 1 -C 6 perfluoroalkyl, O a (C═O) b NR 12 R 13 , oxo, CHO, S(O) m NR 12 R 13 , SH, S(O) m —(C 1 -C 10 )alkyl or (C═O) a O b C 3 -C 8 cycloalkyl, said alkyl, aryl, alkenyl, alkynyl, heterocyclyl, and cycloalkyl optionally substituted with one or more substituents selected from R 11 ;

R 11 is selected from: (C═O) a O b (C 1 -C 10 )alkyl, O a (C 1 -C 3 )perfluoroalkyl, (C 0 -C 6 )alkylene-S(O) m R a , oxo, OH, halo, CN, (C 2 -C 10 )alkenyl, (C 2 -C 10 )alkynyl, (C 3 -C 6 )cycloalkyl, (C 0 -C 6 )alkylene-aryl, (C 0 -C 6 )alkylene-heterocyclyl, (C 0 -C 6 )alkylene-N(R b ) 2 , C(O)R a , (C 0 -C 6 )alkylene-CO 2 R a , C(O)H, and (C 0 -C 6 )alkylene-CO 2 H, said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heterocyclyl is optionally substituted with up to three substituents selected from R b , OH, (C 1 -C 6 )alkoxy, halogen, CO 2 H, CN, O(C═O)C 1 -C 6 alkyl, oxo, and N(R b ) 2 ;

R 12 and R 13 are independently selected from: H, (C═O)O b C 1 -C 10 alkyl, (C═O)O b C 3 -C 8 cycloalkyl, (C═O)O b aryl, (C═O)O b heterocyclyl, C 1 -C 10 alkyl, aryl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, heterocyclyl, C 3 -C 8 cycloalkyl, SO 2 R a , and (C═O) a NR b 2 , said alkyl, cycloalkyl, aryl, heterocylyl, alkenyl, and alkynyl is optionally substituted with one or more substituents selected from R 11 , or R 12 and R 13 can be taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocycle with 3-7 members in each ring and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, said monocyclic or bicyclic heterocycle optionally substituted with one or more substituents selected from R 11 ;

R a is H, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, aryl, or heterocyclyl; and

R b is H, (C 1 -C 6 )alkyl, aryl, heterocyclyl, (C 3 -C 6 )cycloalkyl, (C═O)OC 1 -C 6 alkyl, (C═O)C 1 -C 6 alkyl or S(O) m R a ;

or a pharmaceutically acceptable salt or a stereoisomer thereof.

2. A compound according to Formula

wherein:

R 1 is selected from: S—CH 3 , NHMe, OMe, CN, CONH 2 ,

R Z is selected from: (C 3 -C 8 )cycloalkyl, aryl and heterocyclyl;

or a pharmaceutically acceptable salt or a stereoisomer thereof.

3. A compound according to Formula

wherein,

R Z is selected from:

which are optionally substituted with one to three substituents selected from: oxo, OH, N(R a ) 2 and halogen;

R 1 is

R 10 is selected from: H, C 1 -C 6 alkyl, (C═O)C 1 -C 6 alkyl, (C═O)C 1 -C 6 alkyl-hydroxy, CO 2 H, halo, CN, OH, (C═O)—N(R a ) 2 , CHO, S(O) m N(R a ) 2 , S(O) m —(C 1 -C 6 )alkyl and heterocyclyl, said alkyl and heterocyclyl optionally substituted with one or more: (C 1 -C 6 )alkyl, OH; halo, N(R a ) 2 and COOH;

R a is independently selected from: H and C 1 -C 6 alkyl;

or a pharmaceutically acceptable salt or stereoisomer thereof.

4. A compound which is selected from:

2-(methylthio)-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

2-(methylthio)-6-phenyl-7-(4-{[4-(3-pyridin-3-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

2-(methylthio)-6-phenyl-7-(4-{[4-(5-pyridin-4-yl-1H-pyrazol-3-yl)piperidin-1-yl]methyl} phenyl)pyrido[2,3-d]pyrimidine;

5-(1-{4-[2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]benzyl}piperidin-4-yl)-1,3,4-thiadiazol-2-amine;

1-{4-[2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]benzyl}-N-pyridin-4-ylpiperidine-4-carboxamide;

1-(1-{4-[2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]benzyl}piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;

6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine-2-carboxamide;

N-methyl-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidin-2-amine;

2-methoxy-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine-2-carbonitrile;

2-(4-acetylpiperazin-1-yl)-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

N-cyclobutyl-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1yl]methyl}phenyl)pyrido[2,3-d]pyrimidin-2-amine;

2-morpholin-4-yl-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

2-(3,3-difluoropyrrolidin-1-yl)-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

Methyl-1-[6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidin-2-yl]azetidine-3-carboxylate;

7-(4-{[4-(4-amino-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl]methyl}phenyl)-6-phenylpyrido[2,3-d]pyrimidin-4-amine;

7-(4-{[4-(6-fluoro-1H-benzimidazol-2-yl)piperidin-1-yl]methyl}phenyl)-6-phenylpyrido[2,3-d]pyrimidin-4-amine;

6-phenyl-7-(4-{[4-(5-pyridin-4-yl-1H-pyrazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidin-4-amine;

7-(4-{[4-(6-amino-9H-purin-9-yl)piperidin-1-yl]methyl}phenyl)-6-phenylpyrido[2,3-d]pyrimidin-4-amine;

7-(4-{[4-(2-methyl-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-6-phenylpyrido[2,3-d]pyrimidin-4-amine;

1-{4-[2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]benzyl}piperidine-4-carboxylic acid;

tert-butyl 1-{4-[2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]benzyl}piperidin-4-ylcarbamate;

1-{4-[2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]benzyl}piperidin-4-amine;

1-{4-[2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]benzyl}piperidine-4-carboxamide;

N-ethyl-N′-(1-{4-[2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]benzyl}piperidin-4-yl)urea;

N-2-acetyl-N-1-(1-{4-[2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]benzyl}piperidin-4-yl)glycinamide;

3-{[(1-{4-[2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]benzyl}piperidin-4-yl)carbonyl]amino}propionamide;

tert-butyl 2-{[(1-{4-[2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]benzyl}piperidin-4-yl)carbonyl]amino}ethylcarbamate;

4-(1-{4-[2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]benzyl}piperidin-4-yl)-1,3-thiazol-2-amine;

7-(4-{[4-(2-methoxy-1H-imidazol-4-yl)piperidin-1-yl]methyl}phenyl)-2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidine;

N-[2-(acetylamino)ethyl]-1-{4-[2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]benzyl}piperidine-4-carboxamide;

1-{4-[2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]benzyl}azetidine-3-carbonitrile;

5-(1-{4-[2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7-yl]benzyl}azetidin-3-yl)-1,3,4-thiadiazol-2-amine;

6-phenyl-7-(4-{[4-(3-pyridin-4-yl-1H-pyrazol-5-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine-2-carbonitrile;

2-(methylthio)-6-phenyl-7-(4-{[4-phenyl-4-(2H-tetraazol-5-yl)piperidin-1-yl]methyl} phenyl)pyrido[2,3-d]pyrimidine; and

2-(methylthio)-6-phenyl-7-{4-[(2-pyridin-3-ylpyrrolidin-1-yl)methyl]phenyl}pyrido[2,3-d]pyrimidine;

or a pharmaceutically acceptable salt or a stereoisomer thereof.

5. A compound which is selected from:

N,N-dimethyl-2-(4-{7-[4-({4-[5-(1-oxidopyridin-4-yl)-4H-1,2,4-triazol-3-yl]piperidin-1-yl}methyl)phenyl]-6-phenylpyrido[2,3-d]pyrimidin-2-yl}piperazin-1-yl)ethanamine;

N,N-dimethyl-4-[6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidin-2-yl]piperazine-1-carboxamide;

2-oxo-2-{4-[6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidin-2-yl]piperazine-1-yl}ethanol;

2-[3-(4-methylpiperazin-1-yl)azetidin-1-yl]-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

2-[4-(1-methylazetidin-3-yl)piperazin-1-yl]-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

2-(5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

N-N-dimethyl-2-{4-[6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidin-2-yl]piperazin-1-yl}ethanamine;

1-[6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidin-2-yl]piperidin-4-ol;

2-{4-[6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidin-2-yl]piperazin-1-yl}ethanol;

2-(1,1-dioxidothiomorpholin-4-yl)-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

2-[(3S)-3-methylpiperazin-1-yl]-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

2-[(3R)-3-methylpiperazin-1-yl]-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

N,N,N′-trimethyl-N′-[6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidin-2-yl]ethane-1,2-diamine;

2-[4-(2-methoxyethyl)piperazin-1-yl]-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

{(2S)-4-[6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidin-2-yl]piperazin-2-yl}methanol;

N,N-dimethyl-2-oxo-2-{4-[6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidin-2-yl]piperazin-1-yl}ethanamine;

2-[(2S,5R)-2,5-dimethylpiperazin-1-yl]-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

2-(1,1-dioxidothiomorpholin-4-yl)-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

2-[(2R6S)-2,6-dimethylmorpholin-4-yl]-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

2-[(3R5S)-3,5-dimethylpiperazin-1-yl]-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

2-(4-methylpiperazin-1-yl)-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

6-phenyl-2-piperidin-1-yl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidine;

2-(1H-imidazol-1-yl)-6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-a]pyrimidine;

N,N-dimethyl-1-[6-phenyl-7-(4-{[4-(5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]methyl}phenyl)pyrido[2,3-d]pyrimidin-2-yl]piperidin-4-amine;

or a pharmaceutically acceptable salt or a stereoisomer thereof.

6. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of claim 1 .

7. A pharmaceutical composition made by combining the compound of claim 1 and a pharmaceutically acceptable carrier.