β-lactamyl vasopressin V

1. A compound of the formula

in a hydrate or solvate form, wherein:

n is an integer from 0 to 2;

A is XNH—, or R 5 XN—;

A′ is X′NH—, or R 5′ X′N—;

R 2 is hydrogen or C 1 -C 6 alkyl;

R 3 is a structure selected from the group consisting of

R 4 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 9 cycloalkenyl, limonenyl, pinenyl, C 1 -C 3 alkanoyl, optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(halo C 1 -C 4 alkyl), optionally-substituted aryl(alkoxy C 1 -C 4 alkyl), optionally-substituted aryl(C 2 -C 4 alkenyl), optionally-substituted aryl(halo C 2 -C 4 alkenyl), or optionally-substituted aryl(C 2 -C 4 alkynyl);

X is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, (C 1 -C 4 alkoxy)-(C 1 -C 4 alkyl), optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(C 3 -C 7 cycloalkyl), optionally-substituted indan-1-yl, optionally-substituted indan-2-yl, optionally-substituted 1,2,3,4-tetrahydronaphth-1-yl, optionally-substituted 1,2,3,4-tetrahydronaphth-2-yl, the heterocycle Y, Y—(C 1 -C 4 alkyl), R 7 R 8 N—, and R 7 R 8 N—(C 2 -C 4 alkyl); and

R 5 is selected from the group consisting of hydroxy, C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, and benzyl; or

R 5 and X are taken together with the attached nitrogen atom to form an optionally substituted heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, and homopiperazinyl, where said heterocycle is optionally substituted with R 10 , R 12 , R 7 R 8 N—, or R 7 R 8 N—(C 1 -C 4 alkyl);

X′ is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, (C 1 -C 4 alkoxy)-(C 1 -C 4 alkyl), optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(C 3 -C 7 cycloalkyl), optionally-substituted indan-1-yl, optionally-substituted indan-2-yl, optionally-substituted 1,2,3,4-tetrahydronaphth-1-yl, optionally-substituted 1,2,3,4-tetrahydronaphth-2-yl, the heterocycle Y′, Y′—(C 1 -C 4 alkyl), R 7′ R 8′ N—, and R 7′ R 8′ N—(C 2 -C 4 alkyl); and

R 5′ is selected from the group consisting of hydroxy, C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, and benzyl; or

R 5′ and X′ are taken together with the attached nitrogen atom to form an optionally substituted heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, and homopiperazinyl, where said heterocycle is optionally substituted with R 10 , R 12′ , R 7′ R 8′ N—, or R 7′ R 8′N—(C 1 -C 4 alkyl);

where the heterocycle Y and the heterocycle Y′ are each independently selected from the group consisting of tetrahydrofuryl, morpholinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperazinyl, or quinuclidinyl; where said morpholinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperazinyl, or quinuclidinyl is optionally N-substituted with C 1 -C 4 alkyl or optionally-substituted aryl(C 1 -C 4 alkyl);

R 7 is hydrogen or C 1 -C 6 alkyl; and

R 8 is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, optionally-substituted aryl, or optionally-substituted aryl(C 1 -C 4 alkyl); or

R 7 and R 8 are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, and homopiperazinyl; where said piperazinyl or homopiperazinyl is optionally N-substitued with R 12 ;

R 7′ is hydrogen or C 1 -C 6 alkyl; and

R 8′ is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, optionally-substituted aryl, or optionally-substituted aryl(C 1 -C 4 alkyl); or

R 7′ and R 8′ are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, and homopiperazinyl; where said piperazinyl or homopiperazinyl is optionally N-substituted with R 12′ ;

R 10 and R 11 are each independently chosen from the group consisting of hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 5 alkanoyloxy, benzyloxy, benzoyloxy, diphenylmethoxy, triphenylmethoxy, optionally-substituted aryl, and optionally-substituted aryl(C 1 -C 4 alkyl);

where the C 1 -C 6 alkyl or the C 3 -C 8 cycloalkyl is optionally monosubstituted with a substituent selected from the group consisting of hydroxy, protected carboxy, carbamoyl, thiobenzyl and C 1 -C 4 thioalkyl; and,

where the benzyl of said benzyloxy or said benzoyloxy is optionally substituted with one or two substituents independently selected from the group consisting of C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, hydroxy, cyano, carbamoyl, amino, mono(C 1 -C 4 alkyl)amino, di(C 1 -C 4 alkyl)amino, C 1 -C 4 alkylsulfonylamino, and nitro; and

R 12 and R 12′ are each independently selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 4 alkoxycarbonyl, optionally-substituted aryloxycarbonyl, optionally-substituted aryl(C 1 -C 4 alkyl), and optionally-substituted aryloyl; and

providing that when A is XNH— and the integer n is 0, then A′ is not anilinyl, substituted anilinyl, benzylamino, or substituted benzylamino.

2. The compound of claim 1 wherein A is XNH—.

3. The compound of claim 1 wherein A is R 5 XN—; where R 5 is selected from the group consisting of hydroxy, C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, and benzyl; and where X is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, (C 1 -C 4 alkoxy)-(C 1 -C 4 alkyl), optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(C 3 -C 7 cycloalkyl), optionally-substituted indan-1-yl, optionally-substituted indan-2-yl, optionally-substituted 1,2,3,4-tetrahydronaphth-1-yl, optionally-substituted 1,2,3,4-tetrahydronaphth-2-yl, the heterocycle Y, Y—(C 1 -C 4 alkyl), R 7 R 8 N—, and R 7 R 8 N—(C 2 -C 4 alkyl).

4. The compound of claim 1 wherein A is R 5 XN—, where R 5 and X are taken together with the attached nitrogen atom to form an optionally substituted heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, and homopiperazinyl;

where said heterocycle is optionally substituted with R 10 , R 12 , R 7 R 8 N—, or R 7 R 8 N—(C 1 -C 4 alkyl).

5. The compound of claim 4 wherein R 5 and X are taken together with the attached nitrogen atom to form piperidinyl optionally substituted at the 4-position with hydroxy, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 4 alkoxy, (C 1 -C 4 alkoxy)carbonyl, (hydroxy(C 2 -C 4 alkyloxy))-(C 2 -C 4 alkyl), R 7 R 8 N—, R 7 R 8 N—(C 1 -C 4 alkyl), diphenylmethyl, optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), or piperidin-1-yl(C 1 -C 4 alkyl).

6. The compound of claim 4 wherein R 5 and X are taken together with the attached nitrogen atom to form piperazinyl optionally substituted at the 4-position with C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), α-methylbenzyl, N—(C1-C5 alkyl) acetamid-2-yl, N—(C 3 -C 8 cycloalkyl) acetamid-2-yl, R 7 R 8 N—, or (C 1 -C 4 alkoxy)carbonyl.

7. The compound of claim 4 wherein R 5 and X are taken together with the attached nitrogen atom to form homopiperazinyl optionally substituted in the 4-position with C 1 -C 4 alkyl, aryl, or aryl(C 1 -C 4 alkyl).

8. The compound of claim 1 wherein A is R 5 XN—, where R 5 and X are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinonyl, piperidinonyl, 2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl, 1,2,3,4-tetrahydroisoquinolin-2-yl.

9. The compound of claim 1 wherein A′ is X′NH—.

10. The compound of claim 1 wherein A′ is R 5′ X′N—; where R 5′ is selected from the group consisting of hydroxy, C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, and benzyl; and X′ is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, (C 1 -C 4 alkoxy)-(C 1 -C 4 alkyl), optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(C 3 -C 7 cycloalkyl), optionally-substituted indan-1-yl, optionally-substituted indan-2-yl, optionally-substituted 1,2,3,4-tetrahydronaphth-1-yl, optionally-substituted 1,2,3,4-tetrahydronaphth-2-yl, the heterocycle Y′, Y′—(C 1 -C 4 alkyl), R 7′ R 8′ N—, and R 7′ R 8′ N—(C 2 -C 4 alkyl).

11. The compound of claim 1 wherein A′ is R 5′ X′N—, where R 5′ and X′ are taken together with the attached nitrogen atom to form an optionally substituted heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, and homopiperazinyl;

where said heterocycle is optionally substituted with R 10 , R 12′ , R 7′ R 8′ N—, or R 7′ R 8′ N—(C 1 -C 4 alkyl).

12. The compound of claim 11 wherein R 5′ and X′ are taken together with the attached nitrogen atom to form piperidinyl optionally substituted at the 4-position with hydroxy, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 4 alkoxy, (C 1 -C 4 alkoxy)carbonyl, (hydroxy(C 1 -C 4 alkyloxy))-(C 1 -C 4 alkyl), R 7′ R 8′ N—, R 7′ R 8′ N—(C 1 -C 4 alkyl), diphenylmethyl, optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), or piperidin-1-yl(C 1 -C 4 alkyl).

13. The compound of claim 11 wherein R 5′ and X′ are taken together with the attached nitrogen atom to form piperazinyl optionally substituted at the 4-position with C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), α-methylbenzyl, N—(C1-C5 alkyl) acetamid-2-yl, N—(C 3 -C 8 cycloalkyl) acetamid-2-yl, R 7′ R 8′ N—, or (C 1 -C 4 alkoxy)carbonyl.

14. The compound of claim 11 wherein R 5′ and X′ are taken together with the attached nitrogen atom to form homopiperazinyl optionally substituted in the 4-position with C 1 -C 4 alkyl, aryl, or aryl(C 1 -C 4 alkyl).

15. The compound of claim 1 wherein A′ is R 5′ X′N—, where R 5′ and X′ are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinonyl, piperidinonyl, 2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl, 1,2,3,4-tetrahydroisoquinolin-2-yl.

16. The compound of claim 2 wherein A′ is X′NH—; where X′ is selected from the group consisting of the heterocycle Y′, Y′—(C 1 -C 4 alkyl), R 7′ R 8′ N—, and R 7′ R 8′ N-(C 2 -C 4 alkyl).

17. The compound of claim 16 wherein X is selected from the group consisting of optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(C 3 -C 7 cycloalkyl), the heterocycle Y, Y—(C 1 -C 4 alkyl), R 7 R 8 N—, and R 7 R 8 N—(C 2 -C 4 alkyl).

18. The compound of claim 2 wherein A′ is R 5′ X′N—, where R 5′ and X′ are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, and homopiperazinyl;

where said heterocycle is optionally substituted with R 10 , R 12′ , R 7′ R 8′ N—, or R 7′ R 8′ N—(C 1 -C 4 alkyl).

19. The compound of claim 18 wherein X is selected from the group consisting of optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(C 3 -C 7 cycloalkyl), the heterocycle Y, Y—(C 1 -C 4 alkyl), R 7 R 8 N—, and R 7 R 8 N—(C 2 -C 4 alkyl).

20. The compound of claim 2 wherein A′ is X′NH—, or R 5′ X′N—; and n is 1.

21. The compound of claim 2 wherein A′ is X′NH—, or R 5′ X′N—; and n is 2.

22. The compound of claim 9 wherein A is XNH—; where X is selected from the group consisting of the heterocycle Y, Y—(C 1 -C 4 alkyl), R 7 R 8 N—, and R 7 R 8 N—(C 2 -C 4 -alkyl).

23. The compound of claim 22 wherein X′ is selected from the group consisting of optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(C 3 -C 7 cycloalkyl), the heterocycle Y′, Y′—(C 1 -C 4 alkyl), R 7′ R 8′ N—, and R 7′ R 8′ N—(C 2 -C 4 alkyl).

24. The compound of claim 9 wherein A is R 5 XN—, where R 5 and X are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, and homopiperazinyl;

where said heterocycle is optionally substituted with R 10 , R 12′ , R 7 R 8 N—, or R 7 R 8 N—(C 1 -C 4 alkyl).

25. The compound of claim 24 wherein X′ is selected from the group consisting of optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(C 3 -C 7 cycloalkyl), the heterocycle Y′, Y′—(C 1 -C 4 alkyl), R 7′ R 8′ N—, and R 7′ R 8′ N—(C 2 -C 4 alkyl).

26. The compound of claim 9 wherein A is XNH—, or R 5 XN—; and n is 1.

27. The compound of claim 9 wherein A is XNH—, or R 5 XN—; and n is 2.

28. The compound of claim 1 wherein A is R 5 XN—, where R 5 and X are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, and homopiperazinyl; where said heterocycle is optionally substituted with R 10 , R 12 , R 7 R 8 N—, or R 7 R 8 N—(C 1 -C 4 alkyl); and

A′ is R 5′ X′N—, where R 5′ and X′ are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, and homopiperazinyl; where said heterocycle is optionally substituted with R 10 , R 12′ , R 7′ R 8′ N—, or R 7′ R 8′ N—(C 1 -C 4 alkyl) as defined above.

29. The compound of claim 28 wherein n is 1.

30. The compound of claim 28 wherein n is 2.

31. The compound of claim 1 wherein R 4 is optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(C 2 -C 4 alkenyl), or optionally-substituted aryl(C 2 -C 4 alkynyl).

32. The compound of claim 1 wherein R 3 is the structure

33. The compound of claim 1 wherein R 2 is hydrogen.

34. The compound of claim 1 wherein A is R 5 XN—, where R 5 and X are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, and piperazinyl; where said heterocycle is optionally substituted with C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, R 7 R 8 N—, R 7 R 8 N—(C 1 -C 4 alkyl), optionally-substituted aryl, or optionally-substituted aryl(C 1 -C 4 alkyl).

35. The compound of claim 1 wherein A is XNH—, where X is optionally-substituted aryl(C 1 -C 4 alkyl).

36. The compound of claim 35 wherein R 4 is optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(C 2 -C 4 alkenyl), or optionally-substituted aryl(C 2 -C 4 alkynyl); R 3 is the structure

R 2 is hydrogen.

37. The compound of claim 36 wherein A′ is X′NH—, where X′ is optionally-substituted aryl(C 1 -C 4 alkyl), the heterocycle Y′, Y′—(C 1 -C 4 alkyl), R 7′ R 8′ N—, or R 7′ R 8′ N—(C 2 -C 4 alkyl).

38. The compound of claim 37 wherein X′ is R 7′ R 8′ N— or R 7′ R 8′ N—(C 2 -C 4 alkyl).

39. The compound of claim 37 wherein X′ is the heterocycle Y′ or Y′—(C 1 -C 4 alkyl), where said heterocycle Y′ is selected from the group consisting of pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, and homopiperazinyl, where said heterocycle is optionally N-substituted with optionally-substituted aryl(C 1 -C 4 alkyl).

40. The compound of claim 37 wherein the integer n is 1.

41. The compound of claim 37 wherein R 8′ is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, and aryl(C 1 -C 4 alkyl).

42. The compound of claim 37 wherein R 7′ and R 8′ are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, and homopiperazinyl, where said piperazinyl or homopiperazinyl is optionally substituted at the 4-position with (C 1 -C 4 alkyl), (C 3 -C 8 cycloalkyl), or aryl(C 1 -C 4 alkyl).

43. The compound of claim 36 wherein A′ is R 5′ X′N—.

44. The compound of claim 43 wherein R 5′ is aryl(C 1 -C 4 alkyl), and X′ is selected from the group consisting of optionally-substituted aryl(C 1 -C 4 alkyl), the heterocycle Y′, Y′—(C 1 -C 4 alkyl), R 7′ R 8′ N—, and R 7′ R 8′ N—(C 2 -C 4 alkyl).

45. The compound of claim 43 wherein R 8′ is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, and aryl(C 1 -C 4 alkyl).

46. The compound of claim 43 wherein R 7′ and R 8′ are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, and homopiperazinyl, where said piperazinyl or homopiperazinyl is optionally substituted at the 4-position with (C 1 -C 4 alkyl), (C 3 -C 8 cycloalkyl), or aryl(C 1 -C 4 alkyl).

47. The compound of claim 43 wherein R 5′ and X′ are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidin-1-yl, piperidin-1-yl, piperazin-1-yl, and homopiperazin-1-yl; where said heterocycle is substituted with C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), the heterocycle Y′, Y′—(C 1 -C 4 alkyl), R 7′ R 8′ N—, R 7′ R 8′ N—(C 1 -C 4 alkyl), or R 7′ R 8′ N—C(O)—(C 1 -C 4 alkyl).

48. The compound of claim 43 wherein R 5′ and X′ are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of piperidin-1-yl and piperazin-1-yl, where the heterocycle is substituted with C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, optionally-substituted aryl(C 1 -C 4 alkyl), R 7′ R 8′ N—, or R 7 R 8 N—(C 1 -C 4 alkyl).

49. The compound of claim 48 wherein R 7′ and R 8′ are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, and homopiperazinyl, where said piperazinyl or homopiperazinyl is optionally substituted at the 4-position with (C 1 -C 4 alkyl), (C 3 -C 8 cycloalkyl), or aryl(C 1 -C 4 alkyl).

50. The compound of claim 43 wherein R 5′ and X′ are taken together with the attached nitrogen to form piperazin-1-yl, where said piperazin-1-yl is substituted with C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, or aryl(C 1 -C 4 alkyl).

51. The compound of claim 43 wherein the integer n is 1.

52. The compound of claim 43 wherein the integer n is 2.

53. A compound of the formula

in a hydrate or solvate form, wherein:

n′ is an integer from 1 to 3;

A is XNH—, or R 5 XN—;

R 2 is hydrogen or C 1 -C 6 alkyl;

R 3 is a structure selected from the group consisting of

R 4 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 9 cycloalkenyl, limonenyl, pinenyl, C 1 -C 3 alkanoyl, optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(halo C 1 -C 4 alkyl), optionally-substituted aryl(alkoxy C 1 -C 4 alkyl), optionally-substituted aryl(C 2 -C 4 alkenyl), optionally-substituted aryl(halo C 2 -C 4 alkenyl), or optionally-substituted aryl(C 2 -C 4 alkynyl);

X is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, (C 1 -C 4 alkoxy)-(C 1 -C 4 alkyl), optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(C 3 -C 7 cycloalkyl), optionally-substituted indan-1-yl, optionally-substituted indan-2-yl, optionally-substituted 1,2,3,4-tetrahydronaphth-1-yl, optionally-substituted 1,2,3,4-tetrahydronaphth-2-yl, the heterocycle Y, Y—(C 1 -C 4 alkyl), R 7 R 8 N—, and R 7 R 8 N—(C 2 -C 4 alkyl); and

R 5 is selected from the group consisting of hydroxy, C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, and benzyl; and where X is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, (C 1 -C 4 alkoxy)-(C 1 -C 4 alkyl), optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(C 3 -C 7 cycloalkyl), optionally-substituted indan-1-yl, optionally-substituted indan-2-yl, optionally-substituted 1,2,3,4tetrahydronaphth-1-yl, optionally-substituted 1,2,3,4-tetrahydronaphth-2-yl, the heterocycle Y, Y—(C 1 -C 4 alkyl), R 7 R 8 N—, and R 7 R 8 N—(C 2 -C 4 alkyl); or

R 5 and X are taken together with the attached nitrogen atom to form an optionally substituted heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, and homopiperazinyl, where said heterocycle is optionally substituted with R 10 , R 12 , R 7 R 8 N—, or R 7 R 8 N—(C 1 -C 4 alkyl);

R 6′ is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, (C 1 -C 4 alkoxy)-(C 1 -C 4 alkyl), optionally-substituted aryl(C 1 -C 4 alkyl), Y′—(C 1 -C 4 alkyl), and R 7′ R 8′ N—(C 2 -C 4 alkyl);

where the heterocycle Y and the heterocycle Y′ are each independently selected from the group consisting of tetrahydrofuryl, morpholinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperazinyl, or quinuclidinyl; where said morpholinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperazinyl, or quinuclidinyl is optionally N-substituted with C 1 -C 4 alkyl or optionally-substituted aryl(C 1 -C 4 alkyl);

R 7 is hydrogen or C 1 -C 6 alkyl; and R 8 is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, optionally-substituted aryl, or optionally-substituted aryl(C 1 -C 4 alkyl); or R 7 and R 8 are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, and homopiperazinyl; where said piperazinyl or homopiperazinyl is optionally N-substitued with R 12 ;

R 7′ is hydrogen or C 1 -C 6 alkyl; and R 8′ is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, optionally-substituted aryl, or optionally-substituted aryl(C 1 -C 4 alkyl); or R 7′ and R 8′ are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, and homopiperazinyl; where said piperazinyl or homopiperazinyl is optionally N-substituted with R 12 ′;

R 10 and R 11 are each independently chosen from the group consisting of hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 5 alkanoyloxy, benzyloxy, benzoyloxy, diphenylmethoxy, triphenylmethoxy, optionally-substituted aryl, and optionally-substituted aryl(C 1 -C 4 alkyl);

where the C 1 -C 6 alkyl or the C 3 -C 8 cycloalkyl is optionally monosubstituted with a substituent selected from the group consisting of hydroxy, protected carboxy, carbamoyl, thiobenzyl and C 1 -C 4 thioalkyl; and,

where the benzyl of said benzyloxy or said benzoyloxy is optionally substituted with one or two substituents independently selected from the group consisting of C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, hydroxy, cyano, carbamoyl, amino, mono(C 1 -C 4 alkyl)amino, di(C 1 -C 4 alkyl)amino, C 1 -C 4 alkylsulfonylamino, and nitro; and

R 12 and R 12′ are each independently selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 4 alkoxycarbonyl, optionally-substituted aryloxycarbonyl, optionally-substituted aryl(C 1 —C 4 alkyl), and optionally-substituted aryloyl.

54. The compound of claim 52 wherein A is XNH—.

55. The compound of claim 53 wherein A is R 5 XN—; where R 5 is selected from the group consisting of hydroxy, C 1 -C 6 alkyl, C 1 -C 4 alkoxycarbonyl, and benzyl; and where X is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, (C 1 -C 4 alkoxy)-(C 1 -C 4 alkyl), optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(C 3 -C 7 cycloalkyl), optionally-substituted indan-1-yl, optionally-substituted indan-2-yl, optionally-substituted 1,2,3,4-tetrahydronaphth-1-yl, optionally-substituted 1,2,3,4-tetrahydronaphth-2-yl, the heterocycle Y, Y—(C 1 -C 4 alkyl), R 7 R 8 N—, and R 7 R 8 N—(C 2 -C 4 alkyl).

56. The compound of claim 53 wherein A is R 5 XN—, where R 5 and X are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, and homopiperazinyl;

where said heterocycle is optionally substituted with R 10 , R 12 , R 7 R 8 N—, or R 7 R 8 N—(C 1 -C 4 alkyl).

57. The compound of claim 56 wherein R 5 and X are taken together with the attached nitrogen atom to form piperidinyl optionally substituted at the 4-position with hydroxy, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 4 alkoxy, (C 1 -C 4 alkoxy)carbonyl, (hydroxy(C 2 -C 4 alkyloxy))-(C 2 -C 4 alkyl), R 7 R 8 N—, R 7 R 8 N—(C 1 -C 4 alkyl), diphenylmethyl, optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), or piperidin-1-yl(C 1 -C 4 alkyl).

58. The compound of claim 56 wherein R 5 and X are taken together with the attached nitrogen atom to form piperazinyl optionally substituted at the 4-position with C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, optionally-substituted aryl, optionally-substituted aryl(C 1 -C 4 alkyl), α-methylbenzyl, N—(C1-C5 alkyl) acetamid-2-yl, N—(C 3 -C 8 cycloalkyl) acetamid-2-yl, R 7 R 8 N—, or (C 1 -C 4 alkoxy)carbonyl.

59. The compound of claim 56 wherein R 5 and X are taken together with the attached nitrogen atom to form homopiperazinyl optionally substituted in the 4-position with C 1 -C 4 alkyl, aryl, or aryl(C 1 -C 4 alkyl).

60. The compound of claim 53 wherein A is R 5 XN—, where R 5 and X are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinonyl, piperidinonyl, 2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl, 1,2,3,4-tetrahydroisoquinolin-2-yl.

61. The compound of claim 53 wherein R 4 is optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(C 2 -C 4 alkenyl), or optionally-substituted aryl(C 2 -C 4 alkynyl).

62. The compound of claim 53 wherein R 3 is the structure

63. The compound of claim 53 wherein R 2 is hydrogen.

64. The compound of claim 53 wherein A is R 5 XN—, where R 5 and X are taken together with the attached nitrogen atom to form an heterocycle selected from the group consisting of pyrrolidinyl, piperidinyl, and piperazinyl; where said heterocycle is optionally substituted with C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, R 7 R 8 N—, R 7 R 8 N—(C 1 -C 4 alkyl), optionally-substituted aryl, or optionally-substituted aryl(C 1 -C 4 alkyl).

65. The compound of claim 53 wherein A is XNH—, where X is optionally-substituted aryl(C 1 -C 4 alkyl).

66. The compound of claim 65 wherein R 2 is hydrogen; R 4 is optionally-substituted aryl(C 1 -C 4 alkyl), optionally-substituted aryl(C 2 -C 4 alkenyl), or optionally-substituted aryl(C 2 -C 4 alkynyl); and R 3 is the structure

67. The compound of claim 53 wherein the integer n′ is 1.

68. The compound of claim 53 wherein the integer n′ is 2.

69. A pharmaceutical formulation comprising a compound of claim 1 , and a pharmaceutically acceptable carrier, diluent, or excipient therefor.

70. A pharmaceutical formulation comprising a compound of claim 53 , and a pharmaceutically acceptable carrier, diluent, or excipient therefor.