Pyrimidyl cyclopentanes as Akt protein kinase inhibitors

1. A method of inhibiting Akt-1 protein kinase for treating or lessening the severity of a cancer in a patient, comprising administering to said patient a therapeutically effective amount of 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 ) 1 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 ) t 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 ) 3 S(O) 2 NR 11 R 11 , C 3 -C 6 alkyl, (CH 2 ) t C 3 -C 8 cycloalkyl, (CH 2 ) t C 3 -C 6 heterocyclyl, (CH 2 ) 1 C 6 -C 8 aryl and (CH 2 ) 1 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 method 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 method of claim 1 , wherein m is 2 and n is 1.

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

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

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

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

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

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

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

is selected from:

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

18. The method 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 method 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 ) t 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 method 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 method 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 method of claim 21 , wherein R 4 is methyl, ethyl, n-propyl, iso-propyl, cyclopropyl, cyclobutyl, cyclopentyl, methylcyclopropyl or ethylcyclopropyl.

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

24. The method 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 method of claim 1 , wherein R 4 is selected from:

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

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

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

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

is selected from:

32. The method of claim 1 , wherein R 1 is 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 method of claim 32 , wherein the residue of Formula I having the structure:

is selected from:

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

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

36. The method 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 method 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 )NHR 10 .

38. The method 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 method 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 method 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 method 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 method 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 method 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 method of claim 43 , wherein t is 0.

45. The method 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 ) t 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 method of claim 45 , wherein one of R 6 , R 7 , R 8 and R 9 is selected from:

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

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

50. The method 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. The method of claim 1 wherein the compound of formula I is 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-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine];

5-chloro-1-((5R,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-5H-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-cyc lopenta[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-yl)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. The method of claim 1 wherein the compound of formula I is 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-methylspiro[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[indoline-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. The method of claim 1 , wherein said cancer is susceptible to the inhibition of Akt-1 and one of Akt-2 and Akt-3 kinase.

54. The method of claim 1 , wherein said cancer is a sarcoma.

55. The method of claim 1 , wherein said cancer is a carcinoma.

56. The method of claim 1 , wherein said cancer is squamous cell carcinoma.

57. The method of claim 1 , wherein said cancer is an adenoma or adenocarcinoma.

58. The method of claim 1 , wherein said cancer is breast, ovary, cervix, prostate, testis, penile, genitourinary tract, seminoma, esophagus, larynx, gastric, stomach, gastrointestinal, skin, keratoacanthoma, follicular carcinoma, melanoma, lung, small cell lung carcinoma, non-small cell lung carcinoma (NSCLC), lung adenocarcinoma, squamous carcinoma of the lung, colon, pancreas, thyroid, papillary, bladder, liver, biliary passage, kidney, bone, myeloid disorders, lymphoid disorders, hairy cells, buccal cavity and pharynx (oral), lip, tongue, mouth, salivary gland, pharynx, small intestine, colon, rectum, anal, renal, prostate, vulval, thyroid, large intestine, endometrial, uterine, brain, central nervous system, cancer of the peritoneum, hepatocellular cancer, head cancer, neck cancer, Hodgkin's or leukemia.

59. The method of claim 1 , wherein the residue of Formula I having the structure

is: