Purine inhibitors of human phosphatidylinositol 3-kinase delta

1. A compound of formula I or a pharmaceutically acceptable salt or stereoisomer thereof:

A, B, D, E and G are independently selected from carbon and nitrogen, wherein at least two of A, B, D, E and G are carbon and wherein A, B, D, E and G form an aromatic ring;

R 1 is selected from hydrogen, C 1-5 alkyl, and —(C 0-3 alkyl)C 3-4 cycloalkyl, wherein R 1 is optionally substituted by 0, 1, 2, 3, or 4 groups independently selected from hydrogen, fluoro, chloro, methyl, C 1-3 haloalkyl, amino, O(C═O)R a , O(C═O)OR a and NH(C═O)R a ;

R a is independently selected from C 1-3 alkyl, C 1-3 haloalkyl and —(C 0-3 alkyl)C 3-4 cycloalkyl;

R 2 is selected from pyridinyl, pyrimidinyl, fluoro, pyrazolyl, phenyl, imidazolyl, iodo, and trifluoroethyl, wherein R 2 is substituted with 0, 1, 2, 3, or 4 R 6 substituents;

R 4 is selected from halogen, C 1-10 alkyl, C 2-10 alkynyl, and C 1-10 alkoxy, wherein R 4 is substituted with 0, 1, 2, 3, or 4 substituents selected from OH, halogen, and —CO 2 H;

n is 0, 1, 2, or 3;

v is 0, 1, 2, or 3;

p is 0 or 1;

L is selected from —O—, —NH—, and —N(C 1-3 alkyl)-;

K is selected from a bond, NH, O, C(O), CH 2 , N(C 1 s)alkyl, —C(O)N(R b )—(CH 2 ) m —, S, SO 2 , and C 2-10 alkynylene;

R b is H or C 1-10 alkyl,

m is 0, 1, 2, or 3;

R 3 is independently selected from:

halogen,

C 1-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

aryl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 -C 0-10 alkyl,

C 3-12 cycloalkylC 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

heteroaryl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

(C 1-10 alkyl) 1-2 aminoC 0-10 alkyl,

C 0-10 alkylamino(carbonyl) 0-1 C 0-10 alkyl,

(C 1-10 alkyl) 1-2 aminoC 0-10 alkyl carbonylC 0-10 alkyl,

C 0-10 alkylsulfonylC 0-10 alkyl,

(C 1-10 alkyl)OH, and

C 1-6 haloalkyl;

wherein R 3 is each substituted with 0, 1, 2, 3, or 4 R 5 substituents and each R 5 is independently selected from:

halogen, C 1-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl, C 1-10 heteroalkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl, aryl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl, C 3-12 cycloalkyl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl, heteroaryl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl, (C 3-12 )heterocycloalkyl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl, C 1-10 alkylamino(carbonyl) 0-1 C 0-10 alkyl, C 3-12 cycloalkyl C 0-10 alkylamino(carbonyl) 0-1 C 0-10 alkyl, aryl C 0-10 alkylamino(carbonyl) 0-1 C 0-10 alkyl, heteroaryl C 0-10 alkylamino(carbonyl) 0-1 C 0-10 alkyl, (C 3-12 )heterocycloalkyl C 0-10 alkylamino(carbonyl) 0-1 C 0-10 alkyl, C 0-10 alkylsulfonylC 0-10 alkyl, (C 3-12 )cycloalkylC 0-10 alkylsulfonylC 0-10 alkyl, (C 3-12 )cycloheteroalkylC 0-10 alkylsulfonylC 0-10 alkyl, heteroarylC 0-10 alkylsulfonylC 0-10 alkyl, arylC 0-10 alkylsulfonylC 0-10 alkyl, —CO 2 (C 0-10 alkyl), —(C 0-10 alkyl)CO 2 H, Oxo (═O), —SO 2 N(C 1-6 alkyl) 1-2 , —SO 2 C 1-6 alkyl, —SO 2 CF 3 , —SO 2 CF 2 H, amino, (C 0-10 alkyl) 1-2 amino, hydroxy, (C 1-10 alkyl)OH, C 1-10 alkoxy, cyano, and C 1-6 haloalkyl;

R 6 is independently selected from:

halogen,

C 1-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 1-10 haloalkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 1-10 heteroalkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

aryl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 3-12 cycloalkyl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

heteroaryl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

(C 3-12 )heterocycloalkyl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 0-10 alkyl(oxy) 0-1 carbonylaminoC 0-10 alkyl,

C 0-10 alkylamino(oxy) 0-1 carbonylC 0-10 alkyl,

(C 1-10 )heteroalkylamino(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

C 3-12 cycloalkylamino(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

aryl C 0-10 alkylamino(oxy) 0-1 (carbonyl) 0-1 C 10 alkyl,

heteroaryl C 0-10 alkylamino(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

(C 3-12 )heterocycloalkylamino(oxy) 0-1 (carbonyl) 0-1 C 0-10 alkyl,

—CO 2 (C 0-10 alkyl),

—(C 0-10 alkyl)CO 2 H,

oxo (═O),

C 0-10 alkylsulfonylC 0-10 alkyl,

C 1-10 heteroalkylsulfonylC 0-10 alkyl,

(C 3-12 )cycloalkylC 0-10 alkylsulfonylC 0-10 alkyl,

(C 3-12 )cycloheteroalkylC 0-10 alkylsulfonylC 0-10 alkyl,

heteroarylC 0-10 alkylsulfonylC 0-10 alkyl,

arylC 0-10 alkylsulfonylC 0-10 alkyl,

—SO 2 NH 2 ,

—SO 2 NH(C 1-10 alkyl),

—SO 2 N(C 1-10 alkyl) 2 ,

—SO 2 CF 3 ,

—SO 2 CF 2 H,

amino,

(C 1-10 alkyl) 1-2 amino,

-(oxy) 0-1 (carbonyl) 0-1 N(C 0-10 alkyl) 1-2

hydroxy,

(C 1-10 alkyl)OH,

C 1-10 alkoxy,

(C 1-10 alkyl)cyano,

cyano, and

C 1-6 haloalkyl; and

wherein R 5 and R 6 are each independently substituted with 0, 1, 2, or 3 R 7 substituents and each R 7 substituent is independently selected from hydroxy, (C 1-6 )alkyl, (C 1-6 )alkoxy, (C 5-6 )aryl, (C 5-6 )heteroaryl, (C 1-10 alkyl)OH, halogen, CO 2 H, —(C 0-6 )alkylCN, —O(C═O)C 1 -C 6 alkyl, —(C═O)OC 1 -C 6 alkyl, NO 2 , trifluoromethoxy, trifluoroethoxy, trifluoromethyl, trifluoroethyl, —N—C(O)O(C 0-6 )alkyl, C 1-10 alkylsulfonyl, oxo (O═), aminosulfonyl, —SO 2 N(C 1-6 alkyl) 1-2 , —SO 2 C 1-6 alkyl, —SO 2 CF 3 , —SO 2 CF 2 H, —C 1-10 alkylsulfinyl, —O (0-1) (C 1-10 )haloalkyl, amino(C 1-6 alkyl) 1-2 and NH 2 .

2. A compound according to claim 1 , or a pharmaceutically acceptable salt, or a stereoisomer thereof, wherein R 1 is hydrogen or C 1-5 alkyl optionally substituted by 0, 1, 2, 3, or 4 groups independently selected from hydrogen, C 1-3 haloalkyl, fluoro, chloro, methyl, amino, O(C═O)R a , O(C═O)OR a and NH(C═O)R a .

3. A compound according to claim 2 , or a pharmaceutically acceptable salt, or a stereoisomer thereof, wherein

is selected from:

4. A compound according to claim 3 , or a pharmaceutically acceptable salt, or a stereoisomer thereof, wherein v is 0 or 1; and n is 0, 1, or 2.

5. A compound according to claim 4 , or a pharmaceutically acceptable salt, or a stereoisomer thereof, wherein K is selected from a bond, NH, CH 2 , and —C(O)N(R b )—(CH 2 ) m —.

6. A compound according to claim 5 , or a pharmaceutically acceptable salt, or a stereoisomer thereof, wherein K is a bond.

7. A compound according to claim 6 , a pharmaceutically acceptable salt, or a stereoisomer thereof, wherein L is —NH— or —O—.

8. A compound according to claim 7 , a pharmaceutically acceptable salt, or a stereoisomer thereof, wherein R 1 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, or isopentyl, wherein R 1 is substituted by 0, 1, 2, 3, or 4 groups independently selected from hydrogen, fluoro, chloro, methyl, C 1-3 haloalkyl, amino, O(C═O)R a , O(C═O)OR a and NH(C═O)R a .

9. A compound or a pharmaceutically acceptable salt, or a stereoisomer thereof, wherein said compound is selected from:

N-(3-cyclopropyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl)-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-8-(2-methylpyrimidin-5-yl)-N-[3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]-9H-purin-6-amine;

9-ethyl-N-[3-(1-methylethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-N-[3-ethyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

8-(difluoromethyl)-9-ethyl-N-[3-(1-methylethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]-9H-purin-6-amine;

N-(3-cyclopropyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl)-9-ethyl-8-(1-phenyl-1H-pyrazol-4-yl)-9H-purin-6-amine;

N-(3-cyclopropyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl)-9-ethyl-8-[6-(trifluoromethyl)pyridin-3-yl]-9H-purin-6-amine;

N-(3-cyclopropyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl)-9-ethyl-8-(5-fluoro-6-methoxypyridin-3-yl)-9H-purin-6-amine;

N-(3-cyclopropyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl)-9-ethyl-8-(6-methoxypyridin-3-yl)-9H-purin-6-amine;

N-(3-cyclopropyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl)-8-[6-(difluoromethoxy)pyridin-3-yl]-9-ethyl-9H-purin-6-amine;

N-(3-cyclopropyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl)-9-ethyl-8-(6-methoxy-5-methylpyridin-3-yl)-9H-purin-6-amine;

N-(3-cyclopropyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl)-9-ethyl-8-[4-(trifluoromethoxy)phenyl]-9H-purin-6-amine;

N-(3-cyclopropyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl)-9-ethyl-8-(1-ethyl-5-methyl-1H-pyrazol-4-yl)-9H-purin-6-amine;

9-ethyl-N-[3-(1-methylethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]-8-[6-(trifluoromethyl)pyridin-3-yl]-9H-purin-6-amine;

9-ethyl-N-[3-(1-methylethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]-8-[4-(trifluoromethyl)phenyl]-9H-purin-6-amine;

9-ethyl-8-(5-fluoro-6-methoxypyridin-3-yl)-N-[3-(1-methylethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]-9H-purin-6-amine;

8-(5-chloro-6-methoxypyridin-3-yl)-9-ethyl-N-[3-(1-methylethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]-9H-purin-6-amine;

9-ethyl-N-[3-(1-methylethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]-8-(1-phenyl-1H-pyrazol-4-yl)-9H-purin-6-amine;

8-[4-(difluoromethyl)phenyl]-9-ethyl-N-[-3-(1-methylethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]-9H-purin-6-amine;

9-ethyl-N-[-3-(1-methylethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]-8-[4-(trifluoromethyl)-1H-imidazol-1-yl]-9H-purin-6-amine;

N-[3-cyclopropyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]-9-ethyl-8-iodo-9H-purin-6-amine;

N-(3-cyclopropyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl)-9-ethyl-8-[4-(trifluoromethyl)phenyl]-9H-purin-6-amine;

N-[-3-cyclopropyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]-9-ethyl-8-[6-(methylsulfonyl)pyridin-3-yl]-9H-purin-6-amine;

6-{[3-cyclopropyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]oxy}-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purine;

9-ethyl-6-{[3-(1-methylethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]oxy}-8-(2-methylpyrimidin-5-yl)-9H-purine;

6-{[3-cyclobutyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]oxy}-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purine;

9-ethyl-6-{[3-(1-methylethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-yl]amino}-N-(2,2,2-trifluoroethyl)-9H-purine-8-carboxamide;

N-[-3-cyclopropyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-6-yl]-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

tert-butyl 3-cyclopropyl-5-{[9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-yl]amino}-4,5,6,7-tetrahydro-1H-indazole-1-carboxylate;

N-[3-cyclopropyl-4,5,6,7-tetrahydro-1H-indazol-5-yl]-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

N-{1-[2-(dimethylamino)ethyl]-3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl}-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-N-[3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-N-[5-methyl-3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-N-[3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]-8-[4-(trifluoromethyl)phenyl]-9H-purin-6-amine;

8-(difluoromethyl)-9-ethyl-N-[3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]-9H-purin-6-amine;

9-ethyl-N-[3-(1-methylethyl)-1-propyl-4,5,6,7-tetrahydro-1H-indazol-5-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

2-[5-{[9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-yl]amino}-3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]ethanol;

N-[1-acetyl-3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-N-[3-(1-methylethyl)-1-(phenylcarbonyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

N-{1-[(dimethylamino) acetyl]-3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl}-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

N-[1-(3,3-dimethylbutanoyl)-3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

tert-butyl 5-{[9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-yl]amino}-3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazole-1-carboxylate;

ethyl 5-{[9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-yl]amino}-3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazole-1-carboxylate;

1-methylethyl 5-{[9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-yl]amino}-3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazole-1-carboxylate;

methyl 5-{[9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-yl]amino}-3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazole-1-carboxylate;

2,2,2-trifluoro-1,1-dimethylethyl 5-{[9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-yl]amino}-3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazole-1-carboxylate;

N-tert-butyl-5-{[9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-yl]amino}-3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazole-1-carboxamide;

9-ethyl-N-[3-(1-methylethyl)-1-pyridin-2-yl-4,5,6,7-tetrahydro-1H-indazol-5-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-N-[3-(1-methylethyl)-1-(methylsulfonyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-N-[-2-methyl-3-(1-methylethyl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-N-[-1-methyl-3-(1-methylethyl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

N-(1-benzyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-5-yl)-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

6-[(1,3-diethyl-4,5,6,7-tetrahydro-1H-indazol-5-yl)oxy]-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purine;

N-[3-cyclopropyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-6-yl]-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-N-[3-(1-methylethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-6-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

N-(3-cyclopropyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-6-yl)-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-N-[3-(1-methylethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-6-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-6-[(3-ethyl-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-6-yl)oxy]-8-(2-methylpyrimidin-5-yl)-9H-purine;

N-(1-cyclopropyl-4,5,6,7-tetrahydro-1H-benzimidazol-6-yl)-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

N-(1-cyclopropyl-4,5,6,7-tetrahydro-1H-benzimidazol-6-yl)-9-ethyl-8-[6-(trifluoromethyl)pyridin-3-yl]-9H-purin-6-amine;

N-(1-cyclopropyl-4,5,6,7-tetrahydro-1H-benzimidazol-6-yl)-9-ethyl-8-[4-(trifluoromethyl)phenyl]-9H-purin-6-amine;

N-(1-cyclopropyl-4,5,6,7-tetrahydro-1H-benzimidazol-6-yl)-8-(difluoromethyl)-9-ethyl-9H-purin-6-amine;

N-(1-cyclopropyl-2-methyl-4,5,6,7-tetrahydro-1H-benzimidazol-6-yl)-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

N-(1-cyclopropyl-2-ethyl-4,5,6,7-tetrahydro-1H-benzimidazol-6-yl)-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

6-[(1-cyclopropyl-4,5,6,7-tetrahydro-1H-benzimidazol-6-yl)amino]-9-ethyl-N-(2,2,2-trifluoroethyl)-9H-purine-8-carboxamide;

N-[1-cyclopropyl-2-(difluoromethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-6-yl]-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

N-(2-chloro-1-cyclopropyl-4,5,6,7-tetrahydro-1H-benzimidazol-6-yl)-9-ethyl-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-N-[1-(-3-methoxycyclobutyl)-4,5,6,7-tetrahydro-1H-benzimidazol-6-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-N-[1-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-6-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-N-[4-methyl-1-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-6-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-N-[5-methyl-1-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-6-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine;

9-ethyl-N-[7-methyl-1-(1-methylethyl)-4,5,6,7-tetrahydro-1H-benzimidazol-6-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine; and

9-ethyl-N-[1-(1-methylethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-7-yl]-8-(2-methylpyrimidin-5-yl)-9H-purin-6-amine.

10. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt or stereoisomer thereof and a pharmaceutically acceptable carrier.

11. A pharmaceutical composition according to claim 10 , further comprising one or more other therapeutic agents.