Inhibitors of Akt activity

1. A compound of the Formula A:

wherein:

a is 0 or 1; b is 0 or 1; m is 0, 1 or 2; n is 0, 1, 2 or 3; p is 0, 1 or 2; q is 0, 1, 2 or 3; r is 0 or 1; s is 0 or 1; t is 2, 3, 4, 5 or 6;

R 1 is independently selected from: 1) (C═O) a O b C 1 -C 10 alkyl, 2) (C═O) a O b aryl, 3) C 2 -C 10 alkenyl, 4) C 2 -C 10 alkynyl, 5) (C═O) a O b heterocyclyl, 6) (C═O) a O b C 3 -C 8 cycloalkyl, 7) CO 2 H, 8) halo, 9) CN, 10) OH, 11) O b C 1 -C 6 perfluoroalkyl, 12) O a (C═O) b NR 6 R 7 , 13) NR c (C═O)NR 6 R 7 , 14) S(O) m R a , 15) S(O) 2 NR 6 R 7 , 16) NR c S(O) m R a , 17) oxo, 18) CHO, 19) NO 2 , 20) NR c (C═O)O b R a , 21) O(C═O)O b C 1 -C 10 alkyl, 22) O(C═O)O b C 3 -C 8 cycloalkyl, 23) O(C═O)O b aryl, 24) O(C═O)O b -heterocycle, and 25) O a —P═O(OH) 2 , said alkyl, aryl, alkenyl, alkynyl, heterocyclyl, and cycloalkyl optionally substituted with one or more substituents selected from R z ;

R 2 is independently selected from: 1) (C═O) a O b C 1 -C 10 alkyl, 2) (C═O) a O b aryl, 3) C 2 -C 10 alkenyl, 4) C 2 -C 10 alkynyl, 5) (C═O) a O b heterocyclyl, 6) (C═O) a O b C 3 -C 8 cycloalkyl, 7) CO 2 H, 8) halo, 9) CN, 10) OH, 11) O b C 1 -C 6 perfluoroalkyl, 12) O a (C═O) b NR 6 R 7 , 13) NR c (C═O)NR 6 R 7 , 14) S(O) m R a , 15) S(O) 2 NR 6 R 7 , 16) NR c S(O) m R a , 17) CHO, 18) NO 2 , 19) NR c (C═O)O b R a , 20) O(C═O)O b C 1 -C 10 alkyl, 21) O(C═O)O b C 3 -C 8 cycloalkyl, 22) O(C═O)O b aryl, 23) O(C═O)O b -heterocycle, and 24) O a —P═O(OH) 2 , said alkyl, aryl, alkenyl, alkynyl, heterocyclyl, and cycloalkyl optionally substituted with one, two or three substituents selected from R z ;

R 3 and R 4 are independently selected from: H, C 1 -C 6 -alkyl and C 1 -C 6 -perfluoroalkyl, or

R 3 and R 4 are combined to form —(CH 2 ) t — wherein one of the carbon atoms is optionally replaced by a moiety selected from O, S(O) m , —N(R b )C(O)—, and —N(COR a )—;

R 5 is independently selected from: 1) (C═O) a O b C 1 -C 10 alkyl, 2) (C═O) a O b aryl, 3) C 2 -C 10 alkenyl, 4) C 2 -C 10 alkynyl, 5) (C═O) a O b heterocyclyl, 6) (C═O) a O b C 3 -C 8 cycloalkyl, 7) CO 2 H, 8) halo, 9) CN, 10) OH, 11) O b C 1 -C 6 perfluoroalkyl, 12) O a (C═O) b NR 6 R 7 , 13) NR c (C═O)NR 6 R 7 , 14) S(O) m R a , 15) S(O) 2 NR 6 R 7 , 16) NR c S(O) m R a , 17) oxo, 18) CHO, 19) NO 2 , 20) O(C═O)O b C 1 -C 10 alkyl, 21) O(C═O)O b C 3 -C 8 cycloalkyl, and 22) O a —P═O(OH) 2 , said alkyl, aryl, alkenyl, alkynyl, heterocyclyl, and cycloalkyl optionally substituted with one or more substituents selected from R z ;

R 6 and R 7 are independently selected from: 1) H, 2) (C—O)O b R a , 3) C 1 -C 10 alkyl, 4) aryl, 5) C 2 -C 10 alkenyl, 6) C 2 -C 10 alkynyl, 7) heterocyclyl, 8) C 3 -C 8 cycloalkyl, 9) SO 2 R a , 10) (C═O)NR b 2 , 11) OH, and 12) O a —P═O(OH) 2 , said alkyl, cycloalkyl, aryl, heterocylyl, alkenyl, and alkynyl is optionally substituted with one or more substituents selected from R z ;

R z is selected from: 1) (C═O) r O s (C 1 -C 10 )alkyl, 2) O r (C 1 -C 3 )perfluoroalkyl, 3) (C 0 -C 6 )alkylene-S(O) m R a , 4) oxo, 5) OH, 6) halo, 7) CN, 8) (C═O) r O s (C 2 -C 10 )alkenyl, 9) (C═O) r O s (C 2 -C 10 )alkynyl, 10 ) (C═O) r O s (C 3 -C 6 )cycloalkyl, 11) (C═O) r O s (C 0 -C 6 )alkylene-aryl, 12) (C═O) r O s (C 0 -C 6 )alkylene-heterocyclyl, 13) (C═O) r O s (C 0 -C 6 )alkylene-N(R b ) 2 , 14) C(O)R a , 15) (C 0 -C 6 )alkylene-CO 2 R a , 16) C(O)H, 17) (C 0 -C 6 )alkylene-CO 2 H, 18) C(O)N(R b ) 2 , 19) S(O) m R a , 20) S(O) 2 N(R b ) 2 , 21) NR c (C═O)O b R a , 22) O(C═O)O b C 1 -C 10 alkyl, 23) O(C═O)O b C 3 -C 8 cycloalkyl, 24) O(C═O)O b aryl, 25) O(C═O)O b -heterocycle, and 26) O a —P═O(OH) 2 , 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, N(R b ) 2 and O a —P═O(OH) 2 ;

R a is: substituted or unsubstituted (C 1 -C 6 )alkyl, substituted or unsubstituted (C 2 -C 6 )alkenyl, substituted or unsubstituted (C 2 -C 6 )alkynyl, substituted or unsubstituted (C 3 -C 6 )cycloalkyl, substituted or unsubstituted aryl, (C 1 -C 6 )perfluoroalkyl, 2,2,2-trifluoroethyl, or substituted or unsubstituted heterocyclyl;

R b is: H, (C 1 -C 6 )alkyl, substituted or unsubstituted aryl, substituted or unsubstituted benzyl, substituted or unsubstituted heterocyclyl, (C 3 -C 6 )cycloalkyl, (C═O)OC 1 -C 6 alkyl, (C═O)C 1 -C 6 alkyl or S(O) 2 R a ; and

R c is selected from: 1) H, 2) C 1 -C 10 alkyl, 3) aryl, 4) C 2 -C 10 alkenyl, 5) C 2 -C 10 alkynyl, 6) heterocyclyl, 7) C 3 -C 8 cycloalkyl, and 8) C 1 -C 6 perfluoroalkyl, said alkyl, cycloalkyl, aryl, heterocylyl, alkenyl, and alkynyl is optionally substituted with one or more substituents selected from R z ;

or a pharmaceutically acceptable salt or a stereoisomer thereof.

2. The compound according to claim 1 of the Formula B:

wherein:

R z ′ is selected from: alkyl, cycloalkyl, aryl and heterocyclyl, said alkyl, cycloalkyl, aryl or heterocyclyl is optionally substituted with 1 to 3 R z ;

or a pharmaceutically acceptable salt or a stereoisomer thereof.

3. The compound according to claim 2 of the Formula C:

wherein:

R 6 is selected from: H and (C 1 -C 6 )alkyl;

or a pharmaceutically acceptable salt or a stereoisomer thereof.

4. A compound which is selected from:

5-phenyl-6-[4-({[4-(1,2,3-thiadiazol-4-yl)benzyl]amino}methyl)phenyl]nicotinonitrile;

5-phenyl-6-[4-({[(1S,2R)-2-phenylcyclopropyl]amino}methyl)phenyl]nicotinonitrile;

6-(4-{[(3,4-difluorobenzyl)amino]methyl}phenyl)-5-phenylnicotinonitrile;

6-[4-({[2-(3-fluorophenyl)ethyl]amino}methyl)phenyl]-5-phenylnicotinonitrile;

6-[4-({[2-(4-fluorophenyl)ethyl]amino}methyl)phenyl]-5-phenylnicotinonitrile;

5-phenyl-6-[4-({[(4-phenylmorpholin-2-yl)methyl]amino}methyl)phenyl]nicotinonitrile;

6-[4-({[(4-benzylmorpholin-2-yl)methyl]amino}methyl)phenyl]-5-phenylnicotinonitrile;

6-[4-({methyl[(1-phenyl-1H-pyrazol-4-yl)methyl]amino}methyl)phenyl]-5-ph 1 N-[2-(1-methylpyrrolidin-2-yl)ethyl]-N-{4-[3-phenyl-5-(1H-tetrazol-5-yl)pyridin-2-yl]benzyl}amine;

1-{4-[3-phenyl-5-(1H-tetrazol-5-yl)pyridin-2-yl]phenyl}-N-[4-(1,2,3-thiadiazol-4-yl)benzyl]methanamine;

N-(3,4-difluorobenzyl)-N-{4-[3-phenyl-5-(1H-tetrazol -5-yl)pyridin-2-yl]benzyl}amine;

2-chloro-5-phenyl-6-[4-({[4-(1,2,3-thiadiazol -4-yl)benzyl]amino}methyl)phenyl]nicotinonitrile;

1-(2-Aminophenyl)-3-({4-[5-(5-amino-1,3,4-thiadiazol-2-yl)-3-phenylpyridin-2-yl]benzyl}amino)propan-1-one;

3-({4-[5-cyano-3-phenylpyridin-2-yl]benzyl}amino)-1-phenylpropan-1-one; and

3-({4-[5-(5-amino-1,3,4-thiadiazol-2-yl)-3-phenylpyridin-2-yl]benzyl}amino)-1-phenylpropan-1-one;

or a pharmaceutically acceptable salt or a stereoisomer thereof.

5. The trifluoroacetic acid salt of a compound according to claim 1 which is:

5-phenyl-6-[4-({[4-(1,2,3-thiadiazol-4-yl)benzyl]amino}methyl)phenyl]nicotinonitrile;

5-phenyl-6-[4-({[(1S,2R)-2-phenylcyclopropyl]amino}methyl)phenyl]nicotinonitrile;

6-(4-{[(3,4difluorobenzyl)amino]methyl}phenyl)-5-phenylnicotinonitrile;

6-[4-({[2-(3-fluorophenyl)ethyl]amino}methyl)phenyl]-5-phenylnicotinonitrile;

6-[4-({[2-4-fluorophenyl)ethyl]amino}methyl)phenyl]-5-phenylnicotinonitrile;

5-phenyl-6-[4-({[(4-phenylmorpholin-2-yl)methyl]amino}methyl)phenyl]nicotinonitrile;

6-[4-({[(4-benzylmorpholin-2-yl)methyl]amino}methyl)phenyl]-5-phenylnicotinonitrile;

6-[4-({methyl[(1-phenyl-1H-pyrazol-4-yl)methyl]amino}methyl)phenyl]-5-phenylnicotinonitrile;

N-[2-(1-methylpyrrolidin-2-yl)ethyl]-N-{4-[3-phenyl-5-(1H-tetrazol-5-yl)pyridin-2-yl]benzyl}amine;

1-{4-[3-phenyl-5-(1H-tetrazol-5-yl)pyridin-2-yl]phenyl}-N-[4-(1,2,3-thiadiazol-4-yl)benzyl]methanamine;

N-(3,4-difluorobenzyl)-N-{4-[3-phenyl-5-(1H-tetrazol -5-yl)pyridin-2-yl]benzyl}amine;

1-(2-Aminophenyl)-3-({4-[5-(5-amino-1,3,4-thiadiazol-2-yl)-3-phenylpyridin-2-yl]benzyl}amino)propan-1-one; and

3-({4-[5-(5-amino-1,3,4-thiadiazol-2-yl)-3-phenylpyridin-2-yl]benzyl}amino)-1-phenylpropan-1-one;

or a stereoisomer thereof.

6. A compound according to claim 4 which is:

1-(2-Aminophenyl)-3-({4-[5-(5-amino-1,3,4-thiadiazol-2-yl)-3-phenylpyridin-2-yl]benzyl}amino)propan-1-one;

or a pharmaceutically acceptable salt or a stereoisomer thereof.

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

8. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of claim 4 .

9. A method of treating allergy/asthma which comprises administering to a mamal in need thereof a therapeutically effeecive amount of a compund of claim 1 .

10. A method of treating hyperinsulinism which comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 1 .