Granted Patent B2

US 8,513,436 · App. 13/330,378 · Granted Aug 20, 2013

Inventors: Eric Anderson (Southlake, TX); Gary L. Bolton (Ann Arbor, MI); Bradley Caprathe (Livonia, MI); Xin Jiang (Coppell, TX); Chitase Lee (Ann Arbor, MI); William H. Roark (Ann Arbor, MI); Melean Visnick (Irving, TX)

Assignee: Reata Pharmaceuticals, Inc.

Abstract

Claims (171)

1. A compound of the formula:

wherein:

the atoms labeled 1 and 2 are connected either by a double bond or an epoxidized double bond;

n is 1 or 2;

X is —CN, —CF 3 , or —C(O)R a , wherein R a is —OH, alkoxy (C≦6) , alkylamino (C≦6) , dialkylamino (C≦6) , or —NHS(O) 2 -alkyl (C1-4) ;

R 1 and R 2 are each independently hydrogen, hydroxy, halo, or amino; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups; or

R 1 and R 2 are taken together and are alkanediyl (C≦12) , alkenediyl (C≦12) , alkoxydiyl (C≦12) , alkylaminodiyl (C≦12) , or a substituted version of any of these groups;

R 3 is absent, hydrogen; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) or a substituted version of any of these groups; provided that R 3 is absent when and only when the atom to which it is bound forms part of a double bond;

R 5 is absent, hydrogen; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) or a substituted version of any of these groups; provided that R 5 is absent when and only when the atom to which it is bound forms part of a double bond; and

R 6 is hydrogen, hydroxy, amino, halo, cyano, or oxo; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups;

or a pharmaceutically acceptable salt or tautomer thereof.

2. The compound of claim 1 , further defined by the formula:

wherein:

n is 1 or 2;

X is —CN, —CF 3 , or —C(O)R a , wherein R a is —OH, alkoxy (C≦6) , alkylamino (C≦6) , dialkylamino (C≦6) , or —NHS(O) 2 -alkyl (C1-4) ;

R 1 and R 2 are each independently hydrogen, hydroxy, halo, or amino; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups; or

R 1 and R 2 are taken together and are alkanediyl (C≦12) , alkenediyl (C≦12) , alkoxydiyl (C≦12) , alkylaminodiyl (C≦12) , or a substituted version of any of these groups;

R 3 is absent, hydrogen; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) or a substituted version of any of these groups; provided that R 3 is absent when and only when the atom to which it is bound forms part of a double bond;

R 5 is absent, hydrogen; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) or a substituted version of any of these groups; provided that R 5 is absent when and only when the atom to which it is bound forms part of a double bond; and

R 6 is hydrogen, hydroxy, amino, halo, or cyano; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups;

or a pharmaceutically acceptable salt or tautomer thereof.

3. The compound of claim 1 , further defined by the formula:

wherein:

R 1 and R 2 are each independently hydrogen, hydroxy, halo, or amino; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups; or

R 1 and R 2 are taken together and are alkanediyl (C≦12) , alkenediyl (C≦12) , alkoxydiyl (C≦12) , alkylaminodiyl (C≦12) , or a substituted version of any of these groups;

R 3 is absent, hydrogen; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) or a substituted version of any of these groups; provided that R 3 is absent when and only when the atom to which it is bound forms part of a double bond;

R 5 is absent, hydrogen; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) or a substituted version of any of these groups; provided that R 5 is absent when and only when the atom to which it is bound forms part of a double bond; and

R 6 is hydrogen, hydroxy, amino, halo, or cyano; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups;

or a pharmaceutically acceptable salt or tautomer thereof.

4. The compound of claim 3 , further defined by the formula:

wherein:

R 1 and R 2 are each independently hydrogen, hydroxy, halo, or amino; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups;

R 3 is hydrogen; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) or a substituted version of any of these groups; and

R 6 is hydrogen, hydroxy, amino, halo, or cyano; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups;

or a pharmaceutically acceptable salt or tautomer thereof.

5. The compound of claim 3 , further defined by the formula:

wherein:

R 1 and R 2 are each independently hydrogen, hydroxy, halo, or amino; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups; or

R 1 and R 2 are taken together and are alkanediyl (C≦12) , alkenediyl (C≦12) , alkoxydiyl (C≦12) , alkylaminodiyl (C≦12) , or a substituted version of any of these groups;

R 5 is hydrogen; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) or a substituted version of any of these groups; and

R 6 is hydrogen, hydroxy, amino, halo, or cyano; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) ) heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups;

or a pharmaceutically acceptable salt or tautomer thereof.

6. The compound of claim 1 , wherein the atoms labeled 1 and 2 are connected by a double bond.

7. The compound of claim 1 , wherein the atoms labeled 1 and 2 are connected by an epoxidized double bond.

8. The compound of claim 1 , wherein n is 1.

9. The compound of claim 1 , wherein n is 2.

10. The compound of claim 1 , wherein X is —CN.

11. The compound of claim 1 , wherein R 1 and R 2 are each methyl.

12. The compound of claim 1 , wherein R 1 is methyl and R 2 is hydrogen.

13. The compound of claim 1 , wherein R 1 and R 2 are taken together and are alkanediyl (C≦8) .

14. The compound of claim 1 , wherein R 3 is absent.

15. The compound of claim 1 , wherein R 3 is hydrogen.

16. The compound of claim 1 , wherein R 3 is alkyl (C≦8) , aryl (C≦8) , acyl (C≦8) , or a substituted version of any of these groups.

17. The compound of claim 16 , wherein R 3 is methyl.

18. The compound of claim 16 , wherein R 3 is phenyl.

19. The compound of claim 1 , wherein R 5 is absent.

20. The compound of claim 1 , wherein R 5 is hydrogen.

21. The compound of claim 1 , wherein R 5 is alkyl (C≦8) , aryl (C≦8) , acyl (C≦8) , or a substituted version of any of these groups.

22. The compound of claim 21 , wherein R 5 is methyl, cyclohexyl, or t-butyl.

23. The compound of claim 21 , wherein R 5 is 2-hydroxyethyl or 2,2,2-trifluoroethyl.

24. The compound of claim 21 , wherein R 5 is phenyl.

25. The compound of claim 21 , wherein R 5 is acetyl, methoxycarbonyl, ethoxycarbonyl, or phenylcarbonyl.

26. The compound of claim 1 , wherein R 6 is hydrogen.

27. The compound of claim 1 , wherein R 6 is cyano.

28. The compound of claim 1 , wherein R 6 is halo.

29. The compound of claim 1 , wherein R 6 is alkyl (C≦6) .

30. The compound of claim 29 , wherein R 6 is methyl, isopropyl or cyclohexyl.

31. The compound of claim 1 , wherein R 6 is aryl (C≦8) , heteroaryl (C≦8) or a substituted version of either of these groups.

32. The compound of claim 31 , wherein R 6 is phenyl, methylphenyl or naphthyl.

33. The compound of claim 31 , wherein R 6 is chlorophenyl, fluorophenyl or methoxyphenyl.

34. The compound of claim 31 , wherein R 6 is pyridinyl, pyrimidinyl, methylpyrazolyl, dimethylisoxazolyl, methyltriazolyl, or methyltetrazolyl.

35. The compound of claim 1 , wherein R 6 is aralkyl (C≦12) or substituted aralkyl (C≦12) .

36. The compound of claim 35 , wherein R 6 is benzyl.

37. The compound claim 1 , wherein R 6 is amido (C≦8) .

38. The compound of claim 37 , wherein R 6 is phenylcarbonylamino.

39. The compound claim 1 , wherein R 6 is alkynyl (C≦8) .

40. The compound of claim 39 , wherein R 6 is ethynyl.

41. The compound claim 1 , wherein R 6 is acyl (C≦8) .

42. The compound of claim 41 , wherein R 6 is aminocarbonyl or dimethylaminocarbonyl.

43. The compound claim 1 , wherein R 6 is alkoxy (C≦8) .

44. The compound of claim 43 , wherein R 6 is methoxy.

45. The compound according to any one of claims 3 - 5 , wherein carbon atom 10 is in the R configuration.

46. The compound according to any one of claims 3 - 5 , wherein carbon atom 10 is in the S configuration.

47. The compound according to any one of claims 3 - 5 , wherein carbon atom 5 is in the R configuration.

48. The compound according to any one of claims 3 - 5 , wherein carbon atom 5 is in the S configuration.

49. The compound of claim 1 , further defined as:

50. A compound of the formula:

51. A compound of the formula:

52. A compound of the formula:

wherein:

the atoms labeled 1 and 2 are connected either by a double bond or an epoxidized double bond;

n is 1 or 2;

X is —CN, —CF 3 , or —C(O)R a , wherein R a is —OH, alkoxy (C≦6) , alkylamino (C≦6) , dialkylamino (C≦6) , or —NHS(O) 2 -alkyl (C1-4) ;

R 1 and R 2 are each independently hydrogen, hydroxy, halo, or amino; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups; or

R 1 and R 2 are taken together and are alkanediyl (C≦12) , alkenediyl (C≦12) , alkoxydiyl (C≦12) , alkylaminodiyl (C≦12) , or a substituted version of any of these groups;

R 3 is absent, hydrogen; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) or a substituted version of any of these groups; or R 3 is taken together with R 4 as provided below; provided that R 3 is absent when and only when the atom to which it is bound forms part of a double bond;

R 4 is hydrogen, hydroxy, amino, halo, cyano, or oxo; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups; or R 4 is taken together with either R 3 or R 5 as provided below;

R 5 is absent, hydrogen; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) or a substituted version of any of these groups; or R 5 is taken together with R 4 as provided below; provided that R 5 is absent when and only when the atom to which it is bound forms part of a double bond; and

R 6 is hydrogen, hydroxy, amino, halo, cyano, or oxo; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups;

provided that when R 3 and R 4 are taken together, the compound is further defined by formula Ia:

wherein R 7 is hydrogen, hydroxy, amino, halo, or cyano; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups; or

provided that when R 4 and R 5 are taken together, the compound is further defined by formula Ib:

wherein R 8 is hydrogen, hydroxy, amino, halo, or cyano; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups;

or a pharmaceutically acceptable salt or tautomer thereof.

53. The compound of claim 52 , further defined as:

wherein:

R 1 and R 2 are each independently hydrogen, hydroxy, halo, or amino; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups;

R 4 is hydrogen, hydroxy, amino, halo, or cyano; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups;

R 6 is hydrogen, hydroxy, amino, halo, or cyano; or alkyl (C≦12) , alkenyl (C≦12) , alkynyl (C≦12) , aryl (C≦12) , aralkyl (C≦12) , heteroaryl (C≦12) , heterocycloalkyl (C≦12) , acyl (C≦12) , alkoxy (C≦12) , aryloxy (C≦12) , aralkoxy (C≦12) , heteroaryloxy (C≦12) , acyloxy (C≦12) , alkylamino (C≦12) , dialkylamino (C≦12) , arylamino (C≦12) , aralkylamino (C≦12) , heteroarylamino (C≦12) , amido (C≦12) , or a substituted version of any of these groups;

or a pharmaceutically acceptable salt or tautomer thereof.

54. The compound of claim 52 , wherein the atoms labeled 1 and 2 are connected by a double bond.

55. The compound of claim 52 , wherein the atoms labeled 1 and 2 are connected by an epoxidized double bond.

56. The compound of claim 52 , wherein n is 1.

57. The compound of claim 52 , wherein n is 2.

58. The compound of claim 52 , wherein X is —CN.

59. The compound of claim 52 , wherein R 1 and R 2 are each methyl.

60. The compound of claim 52 , wherein R 1 is methyl and R 2 is hydrogen.

61. The compound of claim 52 , wherein R 1 and R 2 are taken together and are alkanediyl (C≦8) .

62. The compound of claim 52 , wherein R 3 is absent.

63. The compound of claim 52 , wherein R 3 is hydrogen.

64. The compound of claim 52 , wherein R 3 is alkyl (C≦8) , aryl (C≦8) , acyl (C≦8) , or a substituted version of any of these groups.

65. The compound of claim 64 , wherein R 3 is methyl.

66. The compound of claim 64 , wherein R 3 is phenyl.

67. The compound of claim 52 , wherein R 4 is hydrogen.

68. The compound of claim 52 , wherein R 4 is oxo.

69. The compound of claim 52 , wherein R 4 is alkyl (C≦8) , aryl (C≦8) , acyl (C≦8) , alkoxy (C≦8) or a substituted version of any of these groups.

70. The compound of claim 69 , wherein R 4 is methyl, isopropyl, t-butyl, or cyclopropyl.

71. The compound of claim 69 , wherein R 4 is haloalkyl (C≦6) .

72. The compound of claim 69 , wherein R 4 is methoxy or ethoxy.

73. The compound of claim 69 , wherein R 4 is phenyl, chlorophenyl, methylphenyl, or methoxyphenyl.

74. The compound of claim 52 , wherein R 4 is heteroaryl (C≦8) .

75. The compound of claim 74 , wherein R 4 is pyridinyl or pyrimidinyl.

76. The compound of claim 69 , wherein R 4 is ethoxycarbonyl.

77. The compound of claim 52 , wherein R 5 is absent.

78. The compound of claim 52 , wherein R 5 is hydrogen.

79. The compound of claim 52 , wherein R 5 is alkyl (C≦8) , aryl (C≦8) , acyl (C≦8) , or a substituted version of any of these groups.

80. The compound of claim 79 , wherein R 5 is methyl, cyclohexyl, or t-butyl.

81. The compound of claim 79 , wherein R 5 is 2-hydroxyethyl or 2,2,2-trifluoroethyl.

82. The compound of claim 79 , wherein R 5 is phenyl.

83. The compound of claim 79 , wherein R 5 is acetyl, methoxycarbonyl, ethoxycarbonyl, or phenylcarbonyl.

84. The compound of claim 52 , wherein R 6 is hydrogen.

85. The compound of claim 52 , wherein R 6 is cyano.

86. The compound of claim 52 , wherein R 6 is halo.

87. The compound of claim 52 , wherein R 6 is alkyl (C≦6) .

88. The compound of claim 87 , wherein R 6 is methyl, isopropyl or cyclohexyl.

89. The compound of claim 52 , wherein R 6 is aryl (C≦8) , heteroaryl (C≦8) or a substituted version of either of these groups.

90. The compound of claim 89 , wherein R 6 is phenyl, methylphenyl or naphthyl.

91. The compound of claim 89 , wherein R 6 is chlorophenyl, fluorophenyl or methoxyphenyl.

92. The compound of claim 89 , wherein R 6 is pyridinyl, pyrimidinyl, methylpyrazolyl, dimethylisoxazolyl, methyltriazolyl, or methyltetrazolyl.

93. The compound of claim 52 , wherein R 6 is aralkyl (C≦12) or substituted aralkyl (C≦12) .

94. The compound of claim 93 , wherein R 6 is benzyl.

95. The compound claim 52 , wherein R 6 is amido (C≦8) .

96. The compound of claim 95 , wherein R 6 is phenylcarbonylamino.

97. The compound claim 52 , wherein R 6 is alkynyl (C≦8) .

98. The compound of claim 97 , wherein R 6 is ethynyl.

99. The compound claim 52 , wherein R 6 is acyl (C≦8) .

100. The compound of claim 99 , wherein R 6 is aminocarbonyl or dimethylaminocarbonyl.

101. The compound claim 52 , wherein R 6 is alkoxy (C≦8) .

102. The compound of claim 101 , wherein R 6 is methoxy.

103. The compound of claim 52 , wherein R 6 is oxo.

104. The compound of claim 52 , wherein R 7 or R 8 is hydrogen.

105. The compound of claim 52 , wherein R 7 or R 8 is halo.

106. The compound of claim 52 , wherein R 7 or R 8 is aryl (C≦8) .

107. The compound of claim 53 , wherein carbon atom 10 is in the R configuration.

108. The compound of claim 53 , wherein carbon atom 10 is in the S configuration.

109. The compound of claim 53 , wherein carbon atom 5 is in the R configuration.

110. The compound of claim 53 , wherein carbon atom 5 is in the S configuration.

111. The compound of claim 52 , further defined as:

112. A composition comprising:

a) the compound of either claim 1 or claim 52 ; and

b) an excipient.

Assignments (9)

Continuity (2)