Pyrimidyl cyclopentanes as Akt protein kinase inhibitors

1. A compound of Formula I:

and tautomers, resolved enantiomers, resolved diastereomers, metabolites, salts and pharmaceutically acceptable prodrugs thereof, wherein:

R 1 is H, CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , CH═CH 2 , CH 2 OH, CF 3 , CHF 2 , CH 2 F, or C 3 -C 6 cycloalkyl;

R 2 is H, OH, OCH 3 or F;

R 3 is H, F or CH 3 ;

each R 4 is independently selected from H, F, Cl, Br, I, CN, (CH 2 ) t NR 10 R 10 , (CH 2 ) t OR 10 , (CH 2 ) t C(O)R 10 , (CH 2 ) t C(O)OR 10 , (CH 2 ) t C(O)NR 10 R 10 , (CH 2 ) t NR 10 C(O)R 10 , (CH 2 ) t NR 10 C(O)OR 10 , (CH 2 ) 1 NR 10 C(O)NR 10 R 10 , C 1 -C 6 alkyl, (CR 10 R 10 ) t C 3 -C 8 cycloalkyl, (CR 10 R 10 ) t C 3 -C 6 heterocyclyl, (CR 10 R 10 ) t C 6 -C 8 aryl, O(CR 10 R 10 ) t C 6 -C 8 aryl, (CR 10 R 10 ) t C 3 -C 6 heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted by one or more F, Cl, Br, I, CN, C 1 -C 3 alkyl, CF 3 , OH or O(C 1 -C 3 alkyl);

R 5 is H, C 1 -C 6 alkyl, (CR 10 R 10 ) t OR 10 , (CR 10 R 10 ) t NR 10 R 10 , (CH 2 ) t C 3 -C 8 cycloalkyl, (CH 2 ) t C 6 -C 8 aryl, wherein said aryl is optionally substituted by F, Cl, Br or I;

R 6 , R 7 , R 8 and R 9 are independently selected from H, C 1 -C 6 alkyl, (CR 10 R 10 ) t OR 10 , (CR 10 R 10 ) t C 6 -C 8 aryl; wherein said aryl is optionally substituted by F, Cl, Br or I;

R 10 is independently selected from H, OH, O(C 1 -C 3 alkyl), (CH 2 ) t NR 11 R 11 , (CH 2 ) t C(O)NR 11 R 11 , (CH 2 ) t S(O)NR 11 R 11 , (CH 2 ) t S(O) 2 NR 11 R 11 , C 1 -C 6 alkyl, (CH 2 ) t C 3 -C 8 cycloalkyl, (CH 2 ) t C 3 -C 6 heterocyclyl, (CH 2 ) t C 6 -C 8 aryl and (CH 2 ) t C 3 -C 6 heteroaryl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally substituted by one or more F, Cl, Br, I, CN, C 1 -C 3 alkyl, CF 3 , OH, O(C 1 -C 3 alkyl); or

two R 10 are taken together to form oxo or a C 3 -C 6 heterocyclyl;

R 11 is independently selected from H, C 1 -C 3 alkyl, OH, OC 1 -C 3 alkyl, NH 2 , N(C 1 -C 3 alkyl) 2 ; or

two R 11 are taken together to form a C 3 -C 6 heterocyclyl, optionally substituted by methyl or ethyl;

m and n are independently 1, 2 or 3, provided that m and n taken together are 3, 4 or 5;

p is 0,1,2 or 3; and

each t is independently 0, 1, 2, 3 or 4.

2. The compound of claim 1 , wherein R 1 is H, CH 3 , CH 2 CH 3 , CH═CH 2 , CH 2 OH, CF 3 , CHF 2 or CH 2 F.

3. The compound of claim 1 , wherein m is 2 and n is 1.

4. The compound of claim 1 , wherein m is 2 and n is 2.

5. The compound of claim 1 , wherein m is 3 and n is 1.

6. The compound of claim 1 , wherein m is 3 and n is 2.

7. The compound of claim 1 , wherein m is 4 and n is 1.

8. The compound of claim 1 , wherein m and n are independently 1 or 2, provided that m and n taken together are 3.

9. The compound of claim 1 , wherein m and n are independently 1, 2 or 3, provided that m and n taken together are 4.

10. The compound according to claim 1 , wherein p is 1 or 2 and R 4 is F, Cl, Br, I, CN, (CH 2 ) t NR 10 R 10 or (CH 2 ) t OR 10 .

11. The compound of claim 10 , wherein the residue of Formula I having the structure

is selected from:

wherein the wavy lines represent points of attachment of the residue in Formula I.

12. The compound of claim 11 , wherein the residue of Formula I having the structure:

is selected from:

wherein the wavy line represents points of attachment for the residue in Formula I.

13. The compound of claim 10 , wherein the residue of Formula I having the structure

is selected from:

wherein the wavy lines represent points of attachment of the residue in Formula I.

14. The compound of claim 10 , wherein the residue of Formula I having the structure

is selected from:

15. The compound of claim 1 , wherein R 4 is (CR 10 R 10 ) t C 6 -C 8 aryl, wherein said aryl is optionally substituted by F, Cl, Br or I.

16. The compound of claim 15 , wherein R 4 is selected from:

wherein the wavy line represents the point of attachment of R 4 in Formula I;

R 12 is F, Cl, Br or I;

q is 0, 1, 2, 3, 4 or 5; and

R 10 is independently selected from H, OH, O(C 1 -C 3 alkyl), (CH 2 ) t NR 11 R 11 , C 1 -C 6 alkyl, (CH 2 ) t C 3 -C 8 cycloalkyl or (CH 2 ) t C 3 -C 6 heterocyclyl, wherein said cycloalkyl and heterocyclyl are optionally substituted by one or more C 1 -C 3 alkyl; or

two R 10 are taken together to form oxo.

17. The compound of claim 16 , wherein R 4 is selected from

18. The compound of claim 1 , wherein R 4 is O(CR 10 R 10 ) t C 6 -C 8 aryl, wherein said aryl is optionally substituted by F, Cl, Br or I.

19. The compound of claim 18 , wherein t is 0, 1, 2 or 3; R 10 is independently selected from H, OH, O(C 1 -C 3 alkyl) or (CH 2 )NR 11 R 11 , or two R 10 are taken together to form oxo; and R 11 is independently selected from H or C 1 -C 3 alkyl, or two R 11 are taken together to form a C 3 -C 6 heterocyclyl, optionally substituted by methyl or ethyl.

20. The compound of claim 19 , wherein R 4 is selected from:

wherein the wavy line represents the point of attachment of R 4 in Formula I.

21. The compound of claim 1 , wherein R 4 is C 1 -C 6 alkyl or (CR 10 R 10 ) t C 3 -C 8 cycloalkyl, wherein said alkyl and cycloalkyl are optionally substituted by F.

22. The compound of claim 21 , wherein R 4 is methyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, methylcyclopropyl or ethylcyclopropyl.

23. The compound of claim 1 , wherein R 4 is (CH 2 ) t C(O)NR 10 R 10 or (CH 2 )NR 10 C(O)R 10 .

24. The compound of claim 23 , wherein R 4 is selected from:

wherein the wavy line represents the point of attachment of R 4 in Formula I.

25. The compound of claim 1 , wherein R 4 is selected from:

26. The compound of claim 1 , wherein R 1 is H, CH 3 , CH 2 CH 3 or CF 3 ; R 2 is H, F, OH, or OCH 3 ; and R 3 is H, CH 3 or F.

27. The compound of claim 26 , wherein R 1 is H or CH 3 .

28. The compound of claim 26 , wherein R 2 is H, F or OH.

29. The compound of claim 26 , wherein R 3 is H or F.

30. The compound of claim 26 , wherein the residue of Formula I having the structure:

is selected from:

and wherein the wavy line represents the point of attachment of the residue in Formula I.

31. The compound of claim 30 , wherein said residue of Formula I is selected from:

32. The compound of claim 1 , wherein R 1 is H, CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , CH═CH 2 , CH 2 OH, CF 3 , CHF 2 , CH 2 F, or C 3 -C 6 cycloalkyl.

33. The compound of claim 32 , wherein the residue of Formula I having the structure:

is selected from:

34. The compound of claim 1 , wherein R 5 is H.

35. The compound of claim 1 , wherein R 5 is methyl, ethyl, n-propyl, iso-propyl.

36. The compound of claim 1 , wherein R 5 is (CR 10 R 10 ) t OR 10 or (CR 10 R 10 ) t NR 10 R 10 .

37. The compound of claim 36 , wherein (CR 10 R 10 ) t OR 10 is (CR 10 R 10 ) t OH; and (CR 10 R 10 ) t NR 10 R 10 is (CR 10 R 10 ) t NH 2 or (CR 10 R 10 ) t NHR 10 .

38. The compound of claim 37 , wherein R 5 is selected from:

wherein the wavy line represents the point of attachment of R 5 in Formula I.

39. The compound of claim 36 , wherein R 5 is selected from:

wherein the wavy line represents the point of attachment of R 5 in Formula I.

40. The compound of claim 1 , wherein R 5 is (CH 2 ) t C 3 -C 8 cycloalkyl or (CH 2 ) t C 6 -C 8 aryl, wherein said aryl is optionally substituted by F or Cl.

41. The compound of claim 40 , wherein R 5 is selected from:

wherein the wavy line represents the point of attachment of R 5 in Formula I.

42. The compound of claim 1 , wherein one of R 6 , R 7 , R 8 and R 9 is (CR 10 R 10 ) t C 6 -C 8 aryl, wherein said aryl is optionally substituted by F, Cl, Br or I.

43. The compound of claim 42 , wherein (CR 10 R 10 ) t C 6 -C 8 aryl is (CR 10 R 10 ) t phenyl optionally substituted by F, Cl, Br or I.

44. The compound of claim 43 , wherein t is 0.

45. The compound of claim 42 , wherein one of R 6 , R 7 , R 8 and R 9 is selected from:

and the remaining R 6 , R 7 , R 8 and R 9 are H, wherein the wavy line represents the point of attachment in Formula I;

R 12 is F, Cl, Br or I;

q is 0, 1, 2, 3, 4 or 5; and

R 10 is independently selected from H, OH, O(C 1 -C 3 alkyl), (CH 2 )NR 11 R 11 , C 1 -C 6 alkyl, (CH 2 ) t C 3 -C 8 cycloalkyl, (CH 2 ) t C 3 -C 6 heterocyclyl.

46. The compound of claim 45 , wherein one of R 6 , R 7 , R 8 and R 9 is selected from:

47. The compound of claim 45 , wherein one of R 6 , R 7 , R 8 and R 9 is selected from:

48. The compound of claim 1 , wherein one of R 6 , R 7 , R 8 and R 9 is (CR 10 R 10 ) t OR 10 , and the remaining R 6 , R 7 , R 8 and R 9 are H.

49. The compound of claim 48 , wherein)(CR 10 R 10 ) t OR 10 is (CR 10 R 10 ) t OH.

50. The compound of claim 49 , wherein (CR 10 R 10 ) t OH is selected from:

wherein the wavy line represents the point of attachment in Formula I.

51. A compound selected from:

(R)-5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-5-bromo-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

5-chloro-1-((5R,7S)-7-fluoro-5-methyl-6,7-dihydro-51′-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

5-chloro-1-45R,7R)-7-fluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(5R,7R)-4-(5-chlorospiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

(5R,7S)-4-(5-chlorospiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

(R)-5-cyclopropyl-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-carbonitrile;

(R)-N-(3-chlorophenyl)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidin]-5-amine;

(R)-2-(1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-5-yl)acetamide;

(R)-5-(3-fluorobenzyl)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

2-(1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-5-yloxy)-2-phenylethanamine;

(R)-(1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-5-yl)methanamine;

(R)-2-(1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-5-yl)ethanamine;

(S)-5-chloro-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,3′-pyrrolidine];

(R)-5-chloro-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,3′-pyrrolidine];

(R)-4-((R)-5-fluorospiro[indoline-3,3′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine;

(R)-4-(S)-5-fluorospiro[indoline-3,3′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine;

(5R,7R)-4-(5-chloro-1′-methylspiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

(R)-3-(4-chlorophenyl)-3-((R)-5-fluoro-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,3′-piperidine]-1′-yl)propan-1-amine;

(S)-3-(4-chlorophenyl)-3-((R)-5-fluoro-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,3′-piperidine]-1′-yl)propan-1-amine;

(R)-3-(5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-yl)propan-1-amine;

(5R,7R)-4-(5-chlorospiro[indoline-3,3′-pyrrolidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

(2′R,3S)-5-chloro-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-2′-phenylspiro[indoline-3,3′-pyrrolidine];

(2′S,3S)-5-chloro-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-2′-phenylspiro[indoline-3,3′-pyrrolidine];

(5R,7R)-4-((3S,5′S)-5′-(hydroxymethyl)spiro[indoline-3,3′-pyrrolidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

(5R,7R)-4-((3S,5′S)-5′-((R)-(4-chlorophenyl)(hydroxy)methyl)spiro[indoline-3,3′-pyrrolidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

(5R,7R)-4-((3S,5′S)-5′-((S)-(4-chlorophenyl)(hydroxy)methyl)spiro[indoline-3,3′-pyrrolidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

(5R,7R)-4-(2′-benzyl-5-chlorospiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

N-((1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)acetamide;

(5R,7R)-4-(4-((isopropylamino)methyl)spiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

(5R,7R)-4-(4-(aminomethyl)-5-chlorospiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

5-chloro-1-(6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-5-ethoxy-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-5-fluoro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-5-chloro-7-fluoro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-5-chloro-6-fluoro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-5-chloro-4-fluoro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-4,5-difluoro-1-(5-methyl-6,7-dihydro-51′-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-5,6-difluoro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-4-bromo-5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-5-carbonitrile;

(R)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-carbonitrile;

(R)-(1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methanamine;

(R)-(5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methanamine;

(R)-2-(5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-yl)ethanol;

(R)-5-chloro-1′-(4-chlorobenzyl)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-5-chloro-1′-methyl-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-5-chloro-1′-isopropyl-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-5-chloro-1′-(cyclopropylmethyl)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-N-methoxy-2-(1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-5-yl)acetamide;

(R)-N-methyl-2-(1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-5-yl)acetamide;

(R)-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-5-yl)methyl)acetamide;

(R)-2-(1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-5-yl)ethanol;

(R)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-5-carboxamide;

(R)-5-(benzyloxy)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

(R)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidin]-5-ol;

(R)-2-(1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-5-yloxy)acetamide;

2-((R)-5-fluoro-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,3′-piperidine]-1′-yl)ethanol;

(R)-4-((R)-5-fluoro-1′-methylspiro[indoline-3,3′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine;

(5R,7R)-4-(5-chloro-1′-(cyclopropylmethyl)spiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

(5R,7R)-4-(5-(benzyloxy)spiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

(S)-1′-benzyl-5-chloro-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,3′-pyrrolidine];

(R)-1′-benzyl-5-chloro-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,3′-pyrrolidine];

3-(5-fluoro-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,3′-piperidine]-1′-yl)propan-1-amine;

(S)-5-chloro-1′-methyl-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,3′-pyrrolidine];

3-((S)-5-chloro-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,3′-pyrrolidine]-1′-yl)propan-1-amine;

(R)-5-chloro-1′-methyl-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-Y 1 )spiro[indoline-3,3′-pyrrolidine]; and

(5R,7R)-4-(4-((dimethylamino)methyl)spiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

and pharmaceutically acceptable salts thereof.

52. A compound selected from:

(5R,7R)-4-(5-chloro-4-((isopropylamino)methyl)spiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

(R)-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl) methyl)propan-2-amine;

N-((1-((5R,7S)-7-fluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-2-amine;

(R)-2-fluoro-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)ethanamine;

(R)-2-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methylamino)ethanol;

(R)-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl) methyl)cyclopentanamine;

(R)-N-((5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-2-amine;

(R)-N-((5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)cyclopentanamine;

(5R,7R)-4-((S)-4-((isopropylamino)methyl)spiro[indoline-3,3′-pyrrolidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

(5R,7R)-4-((R)-4-((isopropylamino)methyl)spiro[indoline-3,3′-pyrrolidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

(5R,7R)-5-methyl-4-((R)-4-methyl)spiro[indoline-3,3′-pyrrolidine]-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

(R)-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl) methyl)pyrimidin-2-amine;

1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-4-((R)-pyrrolidin-2-yl)spiro[indoline-3,4′-piperidine];

(R)-N-((1-(5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-2-amine;

(S)-N-((1-(5-cyclopentyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-2-amine;

(S)-N-((1-(5-isopropyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-2-amine;

(S)-N-((1-(5-isopropyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indo line-3,4′-piperidine]-4-yl)methyl)cyclopentanamine;

1-(1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)ethanol;

(5R,7R)-4-(4-((isopropylamino)methyl)spiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;

(R)-3,3,3-trifluoro-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-1-amine;

(R)-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)ethanamine;

(R)-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-1-amine;

(R)-1-cyclopropyl-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)methanamine;

(R)-2-methoxy-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)ethanamine;

(R)-N-((1′-methyl-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-2-amine;

(R)-N-methyl-1-(1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methanamine;

(R)-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)tetrahydro-2H-pyran-4-amine;

(R)-2,2-difluoro-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)ethanamine;

(R)-2-methyl-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-1-amine;

N-((1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)butan-2-amine;

(R)-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)pentan-3-amine;

(R)-N-methyl-2-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methylamino)acetamide;

(R)-N-benzyl-1-(1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methanamine;

(R)-4,4-dimethyl-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)cyclohexanamine;

(R)-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)pyridin-2-amine; and

(R)-N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)-N-(pyridin-2-yl)pyridin-2-amine;

and pharmaceutically acceptable salts thereof.

53. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier, adjuvant or vehicle.

54. The composition of claim 53 , further comprising an additional therapeutic agent selected from an anti-proliferative agent, an anti-inflammatory agent, an immunomodulatory agent, a neurotropic factor, an agent for treating cardiovascular disease, an agent for treating liver disease, an anti-viral agent, an agent for treating blood disorders, an agent for treating diabetes, or an agent for treating immunodeficiency disorders.

55. A pharmaceutical composition comprising a compound of claim 1 in an amount to detectably inhibit Akt kinase activity and a pharmaceutically acceptable carrier, adjuvant or vehicle.

56. A kit for treating a hyperproliferative disorder, comprising:

(a) a first pharmaceutical composition comprising a compound of claim 1 ; and

(b) instructions for use.

57. The kit of claim 56 , further comprising:

(c) a second pharmaceutical composition, comprising a second compound having anti-hyperproliferative activity.

58. The kit of claim 57 , wherein said instructions comprise instructions for the simultaneous, sequential or separate administration of said first and second pharmaceutical compositions to a patient in need thereof.

59. The kit of claim 58 , wherein said first and second compositions are contained in separate containers.

60. The kit of claim 58 , wherein said first and second compositions are contained in the same container.