GLUCOKINASE ACTIVATORS

• US 20070197532A1
• Filed: 11/17/2006
• Published: 08/23/2007
• Est. Priority Date: 11/18/2005
• Status: Abandoned Application

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Pharmaceutical Company Limited
• Inventors: Feng, Jun, Takakura, Nobuyuki, Tang, Mingnam, Imaeda, Yasuhiro, Cao, Sheldon, Gwaltney, Stephen, Hosfield, David
• Application Number:
  US11/561,307
• Publication Number:
  US 20070197532A1
• Time in Patent Office: Days
• US Class Current: 514/235.5
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 231/20 One oxygen atom attached in position 3 or 5
• CPC Class Codes: C07D 249/08 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
• CPC Class Codes: C07D 249/12 Oxygen or sulfur atoms
• CPC Class Codes: C07D 249/14 Nitrogen atoms
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 407/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

Compounds, pharmaceutical compositions, kits and methods are provided for use with glucokinase that comprise a compound selected from the group consisting of: wherein the variables are as defined herein.

Claims

1. A compound comprising:

2. The compound of claim 1, wherein the compound comprises

3. The compound of claim 1, wherein the compound comprises

4. The compound of claim 1, wherein the compound comprises

5. The compound of claim 1, wherein the compound comprises

6. The compound of claim 1, wherein the compound comprises

7. The compound of claim 1, wherein the compound comprises

8. The compound of claim 1, wherein the compound comprises

9. The compound of claim 1, wherein the compound comprises

10. The compound according to claim 9, wherein L₁ is absent or L₁ comprises a moiety selected from the group consisting of —

CH₂—

, —

CH₂—

O—

, —

CH═

CH—

, —

CO—

, —

CO—

O—

, —

CO—

NH—

, —

NH—

, —

NH—

CO—

NH—

, —

O—

, —

O—

CH₂—

, —

O—

CH₂—

CO—

, —

S—

, —

S—

CH₂—

, —

S—

CH₂—

CO—

, —

S—

CH₂—

CO—

NH—

, -Ph-O—

, -Ph-CO— and

-Ph-CO—

CH₂, each substituted or unsubstituted.

11. The compound according to claim 9, wherein L₁ is —

O—

.

12. The compound of claim 1, wherein the compound comprises

13. The compound of claim 1, wherein the compound comprises:

14. The compound of claim 1, wherein the compound comprises

15. The compound according to claim 14, wherein L₁ is absent or L₁ comprises a moiety selected from the group consisting of —

CH₂—

, —

CH₂—

O—

, —

CH═

CH—

, —

CO—

, —

CO—

O—

, —

CO—

NH—

, —

NH—

, —

NH—

CO—

NH—

, —

O—

, —

O—

CH₂—

, —

O—

CH₂—

CO—

, —

S—

, —

S—

CH₂—

, —

S—

CH₂—

CO—

, —

S—

CH₂—

CO—

NH—

, -Ph-O—

, -Ph-CO— and

-Ph-CO—

CH₂, each substituted or unsubstituted.

16. The compound according to claim 14, wherein L₁ is —

O—

.

17. The compound of claim 1, wherein the compound comprises

18. The compound according to claim 17, wherein L₁ is absent or L₁ comprises a moiety selected from the group consisting of —

CH₂—

, —

CH₂—

O—

, —

CH═

CH—

, —

CO—

, —

CO—

O—

, —

CO—

NH—

, —

NH—

, —

NH—

CO—

NH—

, —

O—

, —

O—

CH₂—

, —

O—

CH₂—

CO—

, —

S—

, —

S—

CH₂—

, —

S—

CH₂—

CO—

, —

S—

CH₂—

CO—

NH—

, -Ph-O—

, -Ph-CO— and

-Ph-CO—

CH₂, each substituted or unsubstituted.

19. The compound according to claim 17, wherein L₁ is —

O—

.

20. The compound of claim 1, wherein the compound comprises

21. The compound according to claim 20, wherein L₁ is absent or L₁ comprises a moiety selected from the group consisting of —

CH₂—

, —

CH₂—

O—

, —

CH═

CH—

, —

CO—

, —

CO—

O—

, —

CO—

NH—

, —

NH—

, —

NH—

CO—

NH—

, —

O—

, —

O—

CH₂—

, —

O—

CH₂—

CO—

, —

S—

, —

S—

CH₂—

, —

S—

CH₂—

CO—

, —

S—

CH₂—

CO—

NH—

, -Ph-O—

, -Ph-CO— and

-Ph-CO—

CH₂, each substituted or unsubstituted.

22. The compound according to claim 20, wherein L₁ is —

O—

.

23. The compound of claim 1, wherein the compound comprises

24. The compound according to claim 23, wherein L₁ is absent or L₁ comprises a moiety selected from the group consisting of —

CH₂—

, —

CH₂—

O—

, —

CH═

CH—

, —

CO—

, —

CO—

O—

, —

CO—

NH—

, —

NH—

, —

NH—

CO—

NH—

, —

O—

, —

O—

CH₂—

, —

O—

CH₂—

CO—

, —

S—

, —

S—

CH₂—

, —

S—

CH₂—

CO—

, —

S—

CH₂—

CO—

NH—

, -Ph-O—

, -Ph-CO— and

-Ph-CO—

CH₂, each substituted or unsubstituted.

25. The compound according to claim 23, wherein L₁ is —

O—

.

26. The compound of claim 1, wherein the compound comprises:

27. The compound according to claim 26, wherein p is selected from the group consisting of 1, 2, 3, 4 and 5.

28. The compound according to claim 26, wherein p is 2.

29. The compound according to claim 26, wherein L₁ is absent or L₁ comprises a moiety selected from the group consisting of —

CH₂—

, —

CH₂—

O—

, —

CH═

CH—

, —

CO—

, —

CO—

O—

, —

CO—

NH—

, —

NH—

, —

NH—

CO—

NH—

, —

O—

, —

O—

CH₂—

, —

O—

CH₂—

CO—

, —

S—

, —

S—

CH₂—

, —

S—

CH₂—

CO—

, —

S—

CH₂—

CO—

NH—

, -Ph-O—

, -Ph-CO— and

-Ph-CO—

CH₂, each substituted or unsubstituted.

30. The compound according to claim 26, wherein L₁ is —

O—

.

31. The compound of claim 1, wherein the compound comprises

32. The compound according to claim 31, wherein m is 2.

33. The compound according to claim 31, wherein R₄ is selected from the group consisting of halo, nitro, cyano, hydroxy, alkoxy, carbonyl, (C_1-10)alkyl and halo(C_1-10)alkyl, each substituted or unsubstituted, or two R₄ are taken together to form a ring.

34. The compound of claim 1, wherein the compound comprises

35. The compound of claim 1, wherein the compound comprises

36. The compound of claim 1, wherein the compound comprises

37. The compound according to claim 36, wherein R_1c and R_1e are each independently selected from the group consisting of hydrogen, halo, nitro, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, amino, (C_1-10)alkyl, and aryl(C_1-10)alkyl, each substituted or unsubstituted.

38. The compound according to claim 36, wherein R_1c and R_1e are each independently a substituted or unsubstituted (C_1-5)alkoxy.

39. The compound according to claim 36, wherein

R_1c and R_1e are each independently Q-M-;

Q is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, (C_4-12)aryl, hetero(C_1-10)aryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted; and

M is absent or a linker providing 1, 2, 3, 4, 5 or 6 atom separation between Q and the ring to which M is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur.

40. The compound of claim 1, wherein the compound comprises

41. The compound according to claim 40, wherein R_1c and R_1e are each independently selected from the group consisting of hydrogen, halo, nitro, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, amino, (C_1-10)alkyl, and aryl(C_1-10)alkyl, each substituted or unsubstituted.

42. The compound according to claim 40, wherein R_1c and R_1e are each independently a substituted or unsubstituted (C_1-5)alkoxy.

43. The compound according to claim 40, wherein

R_1c and R_1e are each independently Q-M-;

Q is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, (C_4-12)aryl, hetero(C_1-10)aryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted; and

M is absent or a linker providing 1, 2, 3, 4, 5 or 6 atom separation between Q and the ring to which M is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur.

44. The compound of claim 1, wherein the compound comprises

45. The compound according to claim 44, wherein R_1c and R_1e are each independently selected from the group consisting of hydrogen, halo, nitro, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, amino, (C_1-10)alkyl, and aryl(C_1-10)alkyl, each substituted or unsubstituted.

46. The compound according to claim 44, wherein R_1c and R_1e are each independently a substituted or unsubstituted (C_1-5)alkoxy.

47. The compound according to claim 44, wherein

R_1c and R_1e are each independently Q-M-;

Q is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, (C_4-12)aryl, hetero(C_1-10)aryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted; and

M is absent or a linker providing 1, 2, 3, 4, 5 or 6 atom separation between Q and the ring to which M is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur.

48. The compound of claim 1, wherein the compound comprises

49. The compound according to claim 48, wherein L₁ is absent or L₁ comprises a moiety selected from the group consisting of —

CH₂—

, —

CH₂—

O—

, —

CH═

CH—

, —

CO—

, —

CO—

O—

, —

CO—

NH—

, —

NH—

, —

NH—

CO—

NH—

, —

O—

, —

O—

CH₂—

, —

O—

CH₂—

CO—

, —

S—

, —

S—

CH₂—

, —

S—

CH₂—

CO—

, —

S—

CH₂—

CO—

NH—

, -Ph-O—

, -Ph-CO— and

-Ph-CO—

CH₂, each substituted or unsubstituted.

50. The compound according to claim 48, wherein L₁ is —

O—

.

51. The compound according to claim 48, wherein R_1c and R_1e are each independently selected from the group consisting of hydrogen, halo, nitro, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, amino, (C_1-10)alkyl, and aryl(C_1-10)alkyl, each substituted or unsubstituted.

52. The compound according to claim 48, wherein R_1c and R_1e are each independently a substituted or unsubstituted (C_1-5)alkoxy.

53. The compound according to claim 48, wherein

R_1c and R_1e are each independently Q-M-;

Q is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, (C_4-12)aryl, hetero(C_1-10)aryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted; and

M is absent or a linker providing 1, 2, 3, 4, 5 or 6 atom separation between Q and the ring to which M is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur.

54. The compound of claim 1, wherein the compound comprises

55. The compound according to claim 54, wherein L₁ is absent or L₁ comprises a moiety selected from the group consisting of —

CH₂—

, —

CH₂—

O—

, —

CH═

CH—

, —

CO—

, —

CO—

O—

, —

CO—

NH—

, —

NH—

, —

NH—

CO—

NH—

, —

O—

, —

O—

CH₂—

, —

O—

CH₂—

CO—

, —

S—

, —

S—

CH₂—

, —

S—

CH₂—

CO—

, —

S—

CH₂—

CO—

NH—

, -Ph-O—

, -Ph-CO— and

-Ph-CO—

CH₂, each substituted or unsubstituted.

56. The compound according to claim 54, wherein L₁ is —

O—

.

57. The compound according to claim 54, wherein R_1c and R_1e are each independently selected from the group consisting of hydrogen, halo, nitro, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, amino, (C_1-10)alkyl, and aryl(C_1-10)alkyl, each substituted or unsubstituted.

58. The compound according to claim 54, wherein R_1c and R_1e are each independently a substituted or unsubstituted (C_1-5)alkoxy.

59. The compound according to claim 54, wherein

R_1c and R_1e are each independently Q-M-;

Q is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, (C_4-12)aryl, hetero(C_1-10)aryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted; and

M is absent or a linker providing 1, 2, 3, 4, 5 or 6 atom separation between Q and the ring to which M is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur.

60. The compound of claim 1, wherein the compound comprises

61. The compound according to claim 60, wherein L₁ is absent or L₁ comprises a moiety selected from the group consisting of —

CH₂—

, —

CH₂—

O—

, —

CH═

CH—

, —

CO—

, —

CO—

O—

, —

CO—

NH—

, —

NH—

, —

NH—

CO—

NH—

, —

O—

, —

O—

CH₂—

, —

O—

CH₂—

CO—

, —

S—

, —

S—

CH₂—

, —

S—

CH₂—

CO—

, —

S—

CH₂—

CO—

NH—

, -Ph-O—

, -Ph-CO— and

-Ph-CO—

CH₂, each substituted or unsubstituted.

62. The compound according to claim 60, wherein L₁ is —

O—

.

63. The compound according to claim 60, wherein R_1c and R_1e are each independently selected from the group consisting of hydrogen, halo, nitro, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, amino, (C_1-10)alkyl, and aryl(C_1-10)alkyl, each substituted or unsubstituted.

64. The compound according to claim 60, wherein R_1c and R_1e are each independently a substituted or unsubstituted (C_1-5)alkoxy.

65. The compound according to claim 60, wherein

R_1c and R_1e are each independently Q-M-;

Q is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, (C_4-12)aryl, hetero(C_1-10)aryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted; and

M is absent or a linker providing 1, 2, 3, 4, 5 or 6 atom separation between Q and the ring to which M is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur.

66. The compound of claim 1, wherein the compound comprises

67. The compound according to claim 66, wherein L₁ is absent or L₁ comprises a moiety selected from the group consisting of —

CH₂—

, —

CH₂—

O—

, —

CH═

CH—

, —

CO—

, —

CO—

O—

, —

CO—

NH—

, —

NH—

, —

NH—

CO—

NH—

, —

O—

, —

O—

CH₂—

, —

O—

CH₂—

CO—

, —

S—

, —

S—

CH₂—

, —

S—

CH₂—

CO—

, —

S—

CH₂—

CO—

NH—

, -Ph-O—

, -Ph-CO— and

-Ph-CO—

CH₂, each substituted or unsubstituted.

68. The compound according to claim 66, wherein L₁ is —

O—

.

69. The compound according to claim 66, wherein R_1c and R_1e are each independently selected from the group consisting of hydrogen, halo, nitro, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, amino, (C_1-10)alkyl, and aryl(C_1-10)alkyl, each substituted or unsubstituted.

70. The compound according to claim 66, wherein R_1c and R_1e are each independently a substituted or unsubstituted (C_1-5)alkoxy.

71. The compound according to claim 66, wherein

R_1c and R_1e are each independently Q-M-;

Q is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, (C_4-12)aryl, hetero(C_1-10)aryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted; and

M is absent or a linker providing 1, 2, 3, 4, 5 or 6 atom separation between Q and the ring to which M is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur.

72. The compound of claim 1, wherein the compound comprises

73. The compound according to claim 72, wherein L₁ is absent or L₁ comprises a moiety selected from the group consisting of —

CH₂—

, —

CH₂—

O—

, —

CH═

CH—

, —

CO—

, —

CO—

O—

, —

CO—

NH—

, —

NH—

, —

NH—

CO—

NH—

, —

O—

, —

O—

CH₂—

, —

O—

CH₂—

CO—

, —

S—

, —

S—

CH₂—

, —

S—

CH₂—

CO—

, —

S—

CH₂—

CO—

NH—

, -Ph-O—

, -Ph-CO— and

-Ph-CO—

CH₂, each substituted or unsubstituted.

74. The compound according to claim 72, wherein L₁ is —

O—

.

75. The compound according to claim 72, wherein R_1c and R_1e are each independently selected from the group consisting of hydrogen, halo, nitro, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, amino, (C_1-10)alkyl, and aryl(C_1-10)alkyl, each substituted or unsubstituted.

76. The compound according to claim 72, wherein R_1c and R_1e are each independently a substituted or unsubstituted (C_1-5)alkoxy.

77. The compound according to claim 72, wherein

R_1c and R_1e are each independently Q-M-;

Q is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, (C_4-12)aryl, hetero(C_1-10)aryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted; and

M is absent or a linker providing 1, 2, 3, 4, 5 or 6 atom separation between Q and the ring to which M is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur.

78. The compound of claim 1, wherein the compound comprises

79. The compound according to claim 78, wherein R₅ is H.

80. The compound according to claim 78, wherein R₆ is H.

81. The compound according to claim 1, wherein Z is CR₃.

82. The compound according to claim 1, wherein n is selected from the group consisting of 1, 2, 3, 4 and 5.

83. The compound according to claim 1, wherein n is 2.

84. The compound according to claim 1, wherein L is absent or L comprises a moiety selected from the group consisting of —

CH₂—

, —

CH₂—

O—

, —

CH═

CH—

, —

CO—

, —

CO—

O—

, —

CO—

NH—

, —

NH—

, —

NH—

CO—

NH—

, —

O—

, —

O—

CH₂—

, —

O—

CH₂—

CO—

, —

S—

, —

S—

CH₂—

, —

S—

CH₂—

CO—

, —

S—

CH₂—

CO—

NH—

, -Ph-O—

, -Ph-CO— and

-Ph-CO—

CH₂, each substituted or unsubstituted.

85. The compound according to claim 1, wherein L is —

O—

.

86. The compound according to claim 1, wherein L is —

O—

(CH₂)_m—

CO— and

m is selected from the group consisting of 0, 1, 2, 3, 4, and 5.

87. The compound according to claim 1, wherein R₁ is selected from the group consisting of hydrogen, halo, nitro, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, amino, (C_1-10)alkyl, and aryl(C_1-10)alkyl, each substituted or unsubstituted.

88. The compound according to claim 1, wherein at least one R₁ is alkoxy.

89. The compound according to claim 1, wherein at least one R₁ is methoxy.

90. The compound according to claim 1, wherein R₁ is 2-methoxy.

91. The compound according to claim 1, wherein

R₁ is Q-M-;

Q is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, (C_4-12)aryl, hetero(C_1-10)aryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted; and

M is absent or a linker providing 1, 2, 3, 4, 5 or 6 atom separation between Q and the ring to which M is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur.

92. The compound according to claim 91, wherein M is absent or M comprises a moiety selected from the group consisting of —

CH₂—

, —

CH₂—

O—

, —

CH═

CH—

, —

CO—

, —

CO—

O—

, —

CO—

NH—

, —

NH—

, —

NH—

CO—

NH—

, —

O—

, —

O—

CH₂—

, —

O—

CH₂—

CO—

, —

S—

, —

S—

CH₂—

, —

S—

CH₂—

CO—

, —

S—

CH₂—

CO—

NH—

, -Ph-O—

, -Ph-CO— and

-Ph-CO—

CH₂, each substituted or unsubstituted.

93. The compound according to claim 91, wherein M is —

O—

.

94. The compound according to claim 91, wherein M is selected from the group consisting of —

CH₂—

O— and

—

O—

CH₂—

.

95. The compound according to claim 91, wherein Q is a substituted or unsubstituted (C_4-12)aryl.

96. The compound according to claim 95, wherein Q is substituted with a substituent selected from the group consisting of (C_1-5)alkyl, sulfonyl and (C_1-5)alkylsulfonyl.

97. The compound according to claim 91, wherein Q is a substituted or unsubstituted phenyl.

98. The compound according to claim 97, wherein Q is substituted with a substituent selected from the group consisting of (C_1-5)alkyl, sulfonyl and (C_1-5)alkylsulfonyl.

99. The compound according to claim 91, wherein Q is a substituted or unsubstituted hetero(C_1-10)aryl.

100. The compound according to claim 99, wherein Q is substituted with a substituent selected from the group consisting of (C_1-5)alkyl, sulfonyl and (C_1-5)alkylsulfonyl.

101. The compound according to claim 91, wherein Q is a substituted or unsubstituted pyridinyl.

102. The compound according to claim 101, wherein Q is substituted with a substituent selected from the group consisting of (C_1-5)alkyl, sulfonyl and (C_1-5)alkylsulfonyl.

103. The compound according to claim 1, wherein R₂ is selected from the group consisting of hydrogen, hydroxy, carbonyl, amino, (C_1-10)alkyl, (C_3-12)cycloalkyl, heteron (C_3-12)alkyl, aryl and heteroaryl, each substituted or unsubstituted.

104. The compound according to claim 1, wherein R₂ is a substituted or unsubstituted (C_1-5)alkyl.

105. The compound according to claim 1, wherein R₂ is methyl.

106. The compound according to claim 1, wherein

R₂ is NR₅R₆;

and

R₅ and R₆ are each independently selected from the group consisting of hydrogen, oxy, hydroxy, carbonyloxy, (C_1-10)alkoxy, (C_4-12)aryloxy, hetero(C_1-10)aryloxy, carbonyl, oxycarbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, hydroxy(C_1-10)alkyl, carbonyl(C_1-10)alkyl, thiocarbonyl(C_1-10)alkyl, sulfonyl(C_1-10)alkyl, sulfinyl(C_1-10)alkyl, (C_1-10)azaalkyl, imino(C_1-10)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-10)alkyl, aryl(C_1-10)alkyl, hetero(C_1-10)aryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, hetero(C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, (C_4-12)aryl, hetero(C_1-10)aryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted, or R₅ and R₆ are taken together to form a substituted or unsubstituted ring.

107. The compound according to claim 106, wherein R₅ is H.

108. The compound according to claim 106, wherein R₆ is H.

109. The compound according to claim 1, wherein R₃ is H.

110. The compound according to claim 1, wherein the compound is in the form of a pharmaceutically acceptable salt.

113. A pharmaceutical composition comprising as an active ingredient a compound according to claim 1.

114. A pharmaceutical composition comprising a compound according to claim 1, wherein the composition is adapted for administration by a route selected from the group consisting of orally, parenterally, intraperitoneally, intravenously, intraarterially, transdermally, sublingually, intramuscularly, rectally, transbuccally, intranasally, liposomally, via inhalation, vaginally, intraoccularly, via local delivery, subcutaneously, intraadiposally, intraarticularly, and intrathecally.

115. A kit comprising:

a compound of claim 1;

and

instructions which comprise one or more forms of information selected from the group consisting of indicating a disease state for which the compound is to be administered, storage information for the compound, dosing information and instructions regarding how to administer the compound.

116. An article of manufacture comprising:

a compound of claim 1;

and

packaging materials.

117. A therapeutic method comprising administering a compound of claim 1 to a subject.

118. A method of activating glucokinase comprising contacting glucokinase with a compound of claim 1.

119. A method of activating glucokinase comprising causing a compound of claim 1 to be present in a subject in order to activate glucokinase in vivo.

120. A method of activating glucokinase comprising administering a first compound to a subject that is converted in vivo to a second compound wherein the second compound activates glucokinase in vivo, the second compound being a compound according to claim 1.

121. A method of treating a disease state for which increasing glucokinase activity ameliorates the pathology and/or symptomology of the disease state, the method comprising causing a compound of claim 1 to be present in a subject in a therapeutically effective amount for the disease state.

122. A method of treating a disease state for which increasing glucokinase activity ameliorates the pathology and/or symptomology of the disease state, the method comprising administering a compound of claim 1 to a subject, wherein the compound is present in the subject in a therapeutically effective amount for the disease state.

123. A method of treating a disease state for which increasing glucokinase activity ameliorates the pathology and/or symptomology of the disease state, the method comprising administering a first compound to a subject that is converted in vivo to a second compound wherein the second compound activates glucokinase in vivo, the second compound being a compound according to claim 1.

111. A compound selected from the group consisting of:

5-(2-methoxyphenyl)-3-(methylthio)-1H-1,2,4-triazole;

5-(2-ethoxyphenyl)-3-(2-fluorobenzylthio)-1H-1,2,4-triazole;

5-(2-(benzyloxy)phenyl)-3-(2-fluorobenzylthio)-1H-1,2,4-triazole;

5-(2,4-dimethoxyphenyl)-3-(2-fluorobenzylthio)-1H-1,2,4-triazole;

5-(2,5-dimethoxyphenyl)-3-(2-fluorobenzylthio)-1H-1,2,4-triazole;

2-((5-(2-methoxyphenyl)-1H-1,2,4-triazol-3-ylthio)methyl)pyridine;

3-((5-(2-methoxyphenyl)-1H-1,2,4-triazol-3-ylthio)methyl)pyridine;

2-(5-(2-methoxyphenyl)-1H-1,2,4-triazol-3-ylthio)-N,N-dimethylacetamide;

2-(5-(2-isopropoxyphenyl)-1H-1,2,4-triazol-3-ylthio)-1-morpholinoethanone;

2-(5-(2-isopropoxyphenyl)-1H-1,2,4-triazol-3-ylthio)-N,N-dimethylacetamide;

3-(2-fluorobenzyloxy)-5-(2-methoxyphenyl)-1H-pyrazole;

3-(2-fluorobenzyloxy)-5-phenyl-1H-pyrazole;

3-(2-fluorobenzyloxy)-5-(2-fluorophenyl)-1H-pyrazole;

5-(3,5-dimethoxyphenyl)-3-(2-fluorobenzyloxy)-1H-pyrazole;

3-(2-fluorobenzyloxy)-5-o-tolyl-1H-pyrazole;

5-(2,4-dimethoxyphenyl)-3-(2-fluorobenzyloxy)-1H-pyrazole;

3-((2-fluorophenoxy)methyl)-5-(2-methoxyphenyl)-1H-pyrazole;

5-(2-methoxyphenyl)-3-phenyl-1H-pyrazole;

3-cyclopropyl-5-(2-methoxyphenyl)-1H-pyrazole;

3-(4-chlorophenyl)-5-(2-methoxyphenyl)-1H-pyrazole;

2-(3-phenyl-1H-pyrazol-5-yl)phenol;

4-bromo-2-(3-phenyl-1H-pyrazol-5-yl)phenol;

5-(2,3-dimethoxyphenyl)-3-(2-fluorobenzyloxy)-1H-pyrazole;

5-(2,3-dihydrobenzofuran-7-yl)-3-(2-fluorobenzyloxy)-1H-pyrazole;

5-(5-(benzyloxy)-2-isopropoxyphenyl)-3-(2-fluorobenzyloxy)-1H-pyrazole;

5-(2,5-dimethoxyphenyl)-3-(2-fluorobenzyloxy)-1H-pyrazole;

5-(5-fluoro-2-methoxyphenyl)-3-(2-fluorobenzyloxy)-1H-pyrazole;

5-(2-(difluoromethoxy)phenyl)-3-(2-fluorobenzyloxy)-1H-pyrazole;

2-((2-(3-phenyl-1H-pyrazol-5-yl)phenoxy)methyl)pyridine;

(R)-6-((5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)methyl)piperazin-2-one;

2-(5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)acetic acid;

2-(5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)-1-morpholinoethanone;

(5-(2-methoxyphenyl)-1H-pyrazol-3-yl)(morpholino)methanone;

(5-(2,5-dimethoxyphenyl)-1H-pyrazol-3-yl)(morpholino)methanone;

5-(2-methoxyphenyl)-N-phenyl-1H-pyrazole-3-carboxamide;

3-(4-fluorophenyl)-5-(2-((1-methyl-1H-imidazol-2-yl)methoxy)phenyl)-1H-pyrazole;

(3-(5-(2-methoxyphenyl)-1H-pyrazol-3-yl)phenyl)(morpholino)methanone;

3-(5-(2-methoxyphenyl)-1H-pyrazol-3-yl)benzonitrile;

4-(5-(2-methoxyphenyl)-1H-pyrazol-3-yl)benzonitrile;

3-(4-fluorophenyl)-5-(2-phenoxyphenyl)-1H-pyrazole;

3-(4-fluorophenyl)-5-(3-phenoxyphenyl)-1H-pyrazole;

2-(3-(3-(4-fluorophenyl)-1H-pyrazol-5-yl)phenoxy)pyrimidine;

5-(4-(benzyloxy)-2-methoxyphenyl)-3-(4-fluorophenyl)-1H-pyrazole;

2-(3-(5-fluoro-2-methoxyphenyl)-1H-pyrazol-5-yl)pyridine;

3-(3,5-difluoro-2-methoxyphenyl)-5-(4-ethynylphenyl)-1H-pyrazole;

2-(3-(3-fluoro-2-methoxyphenyl)-1H-pyrazol-5-yl)pyridine;

3-(5-fluoro-2-methoxyphenyl)-5-(3-fluorophenyl)-1H-pyrazole;

3-(3-fluoro-2-methoxyphenyl)-5-(3-fluorophenyl)-1H-pyrazole;

5-(3-fluorophenyl)-3-(2-methoxyphenyl)-1H-pyrazole;

5-(4-fluorophenyl)-3-(1-methyl-1H-imidazol-2-yl)-1H-pyrazole;

3-benzyl-5-(2-methoxyphenyl)-4H-1,2,4-triazole;

3-benzyl-5-(4-tert-butylphenyl)-4H-1,2,4-triazole;

N-cyclopentyl-2-(5-methyl-4H-1,2,4-triazol-3-yl)aniline;

3-(2-(isopentyloxy)phenyl)-5-methyl-4H-1,2,4-triazole;

3-(2-(isopentyloxy)phenyl)-5-propyl-4H-1,2,4-triazole;

3-benzyl-5-(2-(isopentyloxy)phenyl)-4H-1,2,4-triazole;

3-benzyl-5-(2-isopropoxyphenyl)-4H-1,2,4-triazole;

5-(2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole;

5-(5-bromo-2-isobutoxyphenyl)-1H-pyrazole;

(E)-5-(2-isobutoxy-5-styrylphenyl)-1H-pyrazole;

5-(2-isobutoxy-5-phenethylphenyl)-1H-pyrazole;

5-(5-(benzyloxy)-2-(1-methoxypropan-2-yloxy)phenyl)-1H-pyrazol-3-ol;

5-(3-(2-fluorobenzyloxy)-5-(4-(methylsulfonyl)phenoxy)phenyl)-1H-pyrazol-3-ol;

(S)-5-(3-(2-fluorobenzyloxy)-5-(1-methoxypropan-2-yloxy)phenyl)-1H-pyrazol-3-ol;

(S)-5-(3-(1-methoxypropan-2-yloxy)-5-(4-(methylsulfonyl)phenoxy)phenyl)-1H-pyrazol-3-ol;

5-(3-(cyclopentyloxy)-5-(4-(methylsulfonyl)phenoxy)phenyl)-1H-pyrazol-3-ol;

5-(3-((3-methylpyridin-2-yl)methoxy)-5-(4-(methylsulfonyl)phenoxy)phenyl)-1H-pyrazol-3-ol;

5-(3-(2-methylbenzyloxy)-5-(4-(methylsulfonyl)phenoxy)phenyl)-1H-pyrazol-3-ol;

5-(5-(benzyloxy)-2-(1-methoxypropan-2-yloxy)phenyl)-3-methoxy-1H-pyrazole;

(S)-5-(3-(2-fluorobenzyloxy)-5-(1-methoxypropan-2-yloxy)phenyl)-3-methoxy-1H -pyrazole;

5-(3-(2-fluorobenzyloxy)-5-(4-(methylsulfonyl)phenoxy)phenyl)-3-methoxy-1H-pyrazole;

5-(3-(cyclopentyloxy)-5-(4-(methylsulfonyl)phenoxy)phenyl)-3-methoxy-1H-pyrazole;

2-((3-(3-methoxy-1H-pyrazol-5-yl)-5-(4-(methylsulfonyl)phenoxy)phenoxy)methyl)-3-methylpyridine;

3-methoxy-5-(3-(2-methylbenzyloxy)-5-(4-(methylsulfonyl)phenoxy)phenyl)-1H-pyrazole;

5-(2-(5-(5-(benzyloxy)-2-(1-methoxypropan-2-yloxy)phenyl)-1H-pyrazol-3-yloxy)ethyl)-4-methylthiazole;

(S)-5-(2-(5-(3-(2-fluorobenzyloxy)-5-(1-methoxypropan-2-yloxy)phenyl)-1H-pyrazol-3-yloxy)ethyl)-4-methylthiazole;

(S)-methyl 2-(5-(3-(1-methoxypropan-2-yloxy)-5-(4-(methylsulfonyl)phenoxy)phenyl)-1H-pyrazol-3-yloxy)acetate;

3-(3-methoxy-1H-pyrazol-5-yl)-4-(1-methoxypropan-2-yloxy)phenol;

3-(3-methoxy-1H-pyrazol-5-yl)-5-(4-(methylsulfonyl)phenoxy)phenol;

(S)-3-(3-methoxy-1H-pyrazol-5-yl)-5-(1-methoxypropan-2-yloxy)phenol;

5-(5-ethoxy-2-(1-methoxypropan-2-yloxy)phenyl)-3-methoxy-1H-pyrazole;

3-methoxy-5-(2-(1-methoxypropan-2-yloxy)-5-(2-(thiophen-3-yl)ethoxy)phenyl)-1H -pyrazole;

3-methoxy-5-(2-(1-methoxypropan-2-yloxy)-5-(4-(methylsulfonyl)benzyloxy)phenyl)-1H-pyrazole;

4-((3-(3-methoxy-1H-pyrazol-5-yl)-4-(1-methoxypropan-2-yloxy)phenoxy)methyl)pyridine;

(S)-3-methoxy-5-(3-(1-methoxypropan-2-yloxy)-5-(4-(methylsulfonyl)phenoxy)phenyl)-1H-pyrazole;

(S)-3-methoxy-5-(3-(1-methoxypropan-2-yloxy)-5-(4-(methylsulfonyl)benzyloxy)phenyl)-1H-pyrazole;

(S)-3-methoxy-5-(3-(1-methoxypropan-2-yloxy)-5-(2-(thiophen-3-yl)ethoxy)phenyl)-1H-pyrazole;

(S)-2-(5-(3-(1-methoxypropan-2-yloxy)-5-(4-(methylsulfonyl)phenoxy)phenyl)-1H -pyrazol-3-yloxy)acetic acid;

(S)-1-(4-acetylpiperazin-1-yl)-2-(5-(3-(1-methoxypropan-2-yloxy)-5-(4-(methylsulfonyl)phenoxy)phenyl)-1H-pyrazol-3-yloxy)ethanone;

(S)-2-(5-(3-(1-methoxypropan-2-yloxy)-5-(4-(methylsulfonyl)phenoxy)phenyl)-1H -pyrazol-3-yloxy)-1-morpholinoethanone;

(S)—

N-ethyl-2-(5-(3-(1-methoxypropan-2-yloxy)-5-(4-(methylsulfonyl)phenoxy)phenyl)-1H-pyrazol-3-yloxy)acetamide;

1-isobutyl-6-(1H-pyrazol-5-yl)-1H-benzo [d]imidazole;

1-(cyclohexylmethyl)-6-(1H-pyrazol-5-yl)-1H-benzo[d]imidazole;

5-(1-isobutyl-1H-benzo[d]imidazol-6-yl)-1H-pyrazol-3-ol;

5-(1-(cyclohexylmethyl)-1H-benzo [d]imidazol-6-yl)-1H-pyrazol-3-ol;

1-isobutyl-6-(3-methoxy-1H-pyrazol-5-yl)-1H-benzo[d]imidazole;

1-(cyclohexylmethyl)-6-(3-methoxy-1H-pyrazol-5-yl)-1H-benzo[d]imidazole;

5-benzyl-3-phenyl-1H-1,2,4-triazole;

2-(3-phenyl-1H-1,2,4-triazol-5-yl)phenol;

(3-(2-ethoxyphenyl)-1H-1,2,4-triazol-5-yl)methanol;

1-(4-(methylthio)phenyl)-3-(5-phenyl-1H-1,2,4-triazol-3-yl)urea;

1-(5-phenyl-1H-1,2,4-triazol-3-yl)-3-(2-(trifluoromethyl)phenyl)urea;

1-(2,5-difluorophenyl)-3-(5-phenyl-1H-1,2,4-triazol-3-yl)urea;

5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazol-3-amine;

N-(5-bromopyridin-2-yl)-2-(3-phenyl-1H-1,2,4-triazol-5-ylthio)acetamide;

2,2′

-(1H-1,2,4-triazole-3,5-diyl)diphenol;

1-(3,4-dihydroxyphenyl)-2-(5-(2-methoxyphenyl)-1H-1,2,4-triazol-3-ylthio)ethanone;

2-(5-(2-chlorophenyl)-1H-1,2,4-triazol-3-ylthio)-N-cyclohexylacetamide;

(E)-2-(3-(4-bromostyryl)-1H-1,2,4-triazol-5-yl)phenol;

(E)-2-(3-(2-chlorostyryl)-1H-1,2,4-triazol-5-yl)phenol;

(E)-2-(3-(2-(3-methylthiophen-2-yl)vinyl)-1H-1,2,4-triazol-5-yl)phenol;

(E)-5-(2-(5-(2-hydroxyphenyl)-1H-1,2,4-triazol-3-yl)vinyl)-2-methoxyphenol;

3-(2-fluorobenzylthio)-5-(2-methoxyphenyl)-1H-1,2,4-triazole;

N-(3,4-dimethylphenyl)-2-(5-(2-methoxyphenyl)-1H-1,2,4-triazol-3-ylthio)acetamide;

N-(5-(3,4-dimethoxyphenyl)-1H-1,2,4-triazol-3-yl)-4,6-dimethylpyrimidin-2-amine;

2-(3-phenyl-1H-1,2,4-triazol-5-ylthio)-N-p-tolylacetamide;

3-(4-chlorophenyl)-1H-1,2,4-triazol-5-amine;

N-phenyl-2-(3-phenyl-1H-1,2,4-triazol-5-ylthio)acetamide;

N-(2-nitrophenyl)-2-(3-phenyl-1H-1,2,4-triazol-5-ylthio)acetamide;

N-(3,5-dibromopyridin-2-yl)-2-(3-phenyl-1H-1,2,4-triazol-5-ylthio)acetamide;

3-(2,4-dinitrophenyl)-1H-1,2,4-triazol-5-amine;

3-(2-fluorophenyl)-1H-1,2,4-triazol-5-amine;

N-(2,4-dimethylphenyl)-2-(3-(3-nitrophenyl)-1H-1,2,4-triazol-5-ylthio)acetamide;

3-(2-methoxyphenyl)-1H-1,2,4-triazol-5-amine;

3-(3,5-dimethoxyphenyl)-1H-1,2,4-triazol-5-amine;

5-(1H-pyrrol-2-yl)-3-(thiophen-2-yl)-1H-1,2,4-triazole;

N-(5-(2-methoxyphenyl)-1H-1,2,4-triazol-3-yl)-4,6-dimethylpyrimidin-2-amine;

3-(3-bromobenzylthio)-5-(2-methoxyphenyl)-1H-1,2,4-triazole;

2-(5-(2-methoxyphenyl)-1H-1,2,4-triazol-3-ylthio)-1-morpholinoethanone;

4-((5-(2-methoxyphenyl)-1H-1,2,4-triazol-3-ylthio)methyl)benzoic acid;

2-(5-(2-methoxyphenyl)-1H-1,2,4-triazol-3-ylthio)-N-(2-nitrophenyl)acetamide;

3-benzyl-5-(2-methoxyphenyl)-1H-1,2,4-triazole;

5-benzyl-3-(4-tert-butylphenyl)-1H-1,2,4-triazole;

N-cyclopentyl-2-(5-methyl-1H-1,2,4-triazol-3-yl)aniline;

2-(5-(2-isopropoxyphenyl)-1H-1,2,4-triazol-3-ylthio)acetic acid;

2-(5-(2-isopropoxyphenyl)-1H-1,2,4-triazol-3-ylthio)acetamide;

4-bromo-2-(1H-pyrazol-5-yl)phenol;

5-methyl-3-phenyl-1H-pyrazole-4-carboxamide;

4-chloro-2-(3-methyl-1H-pyrazol-5-yl)aniline;

3,5-diphenyl-1H-pyrazole;

2,4-difluoro-6-(1H-pyrazol-5-yl)phenol;

3-(4-chlorophenyl)-5-(3-phenyl-1H-pyrazol-4-yl)-1,2,4-oxadiazole;

4-ethyl-6-(4-(thiazol-4-yl)-1H-pyrazol-3-yl)benzene-1,3-diol;

4-methyl-6-(4-(2-methylthiazol-4-yl)-1H-pyrazol-3-yl)benzene-1,3-diol;

5-methoxy-3-methyl-2-(5-methyl-4-phenoxy-1H-pyrazol-3-yl)phenol;

4-(4-(4-methoxyphenyl)-5-methyl-1H-pyrazol-3-yl)benzene-1,3-diol;

3-(4-chlorophenyl)-5-(trifluoromethyl)-1H-pyrazole;

3-phenyl-1H-pyrazol-5-ol;

3,5-diphenyl-1H-pyrazol-4-ol;

5-(pyridin-2-yl)-1H-pyrazole-3-carboxylic acid;

2-(3-phenyl-1H-pyrazol-5-yl)pyridine;

N-(3-acetamidophenyl)-5-(pyridin-2-yl)-1H-pyrazole-3-carboxamide;

N-phenyl-5-(pyridin-2-yl)-1H-pyrazole-3-carboxamide;

N-(3-nitrophenyl)-5-(pyridin-2-yl)-1H-pyrazole-3-carboxamide;

N-(5-methylthiazol-2-yl)-5-(pyridin-2-yl)-1H-pyrazole-3-carboxamide;

5-(2,5-bis(2,2,2-trifluoroethoxy)phenyl)-1H-pyrazole;

3-(5-bromo-2-isobutoxyphenyl)-1H-pyrazole;

2-(5-methyl-1H-pyrazol-3-yl)-1H-benzo[d]imidazole;

2-(5-methyl-1H-pyrazol-3-yl)-1H-benzo[d]imidazol-4-ol;

2-(5-methyl-1H-pyrazol-3-yl)benzo[d]oxazol-4-amine;

7-bromo-2-(5-methyl-1H-pyrazol-3-yl)-3H-imidazo[4,5-c]pyridine;

2-(3-methyl-1H-pyrazol-5-yl)-7-phenyl-3H-imidazo[4,5-c]pyridine;

7-(3-(ethylsulfonyl)phenyl)-2-(5-methyl-1H-pyrazol-3-yl)-3H-imidazo[4,5-c]pyridine;

7-(1-(ethylsulfonyl)-1H-indol-6-yl)-2-(5-methyl-1H-pyrazol-3-yl)-3H-imidazo[4,5-c]pyridine;

N-(4-(2-(5-methyl-1H-pyrazol-3-yl)-3H-imidazo[4,5-c]pyridin-7-ylthio)phenyl)acetamide;

(E)-3-(2-isobutoxy-5-styrylphenyl)-1H-pyrazole;

5-(2,5-dimethoxyphenyl)-1H-pyrazole-3-carboxylic acid;

ethyl 5-phenyl-1H-pyrazole-3-carboxylate;

3-(2-isobutoxy-5-phenethylphenyl)-1H-pyrazole;

ethyl 5-(2-methoxyphenyl)-1H-pyrazole-3-carboxylate;

(5-(2-methoxyphenyl)-1H-pyrazol-3-yl)methanol;

2-(5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)acetic acid;

5-(3-fluorophenyl)-3-(1-methyl-1H-imidazol-2-yl)-1H-pyrazole;

3-(3,5-difluoro-2-methoxyphenyl)-5-(3-fluorophenyl)-1H-pyrazole;

2-(3-(3,5-difluoro-2-methoxyphenyl)-1H-pyrazol-5-yl)pyridine;

3,5-di(pyridin-2-yl)-1H-pyrazole;

ethyl 2-(5-(5-chloro-2-methoxyphenyl)-1H-1,2,4-triazol-3-ylthio)acetylcarbamate;

(R)-tert-butyl 3-((5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)methyl)-5-oxopiperazine-1-carboxylate;

3-(4-fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazole;

5-(2,3-dihydrobenzofuran-7-yl)-3-phenyl-1H-pyrazole;

5-(2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)-3-phenyl-1H-pyrazole;

5-(5-bromo-2,3-dihydrobenzofuran-7-yl)-3-phenyl-1H-pyrazole;

4-(3-phenyl-1H-pyrazol-5-yl)benzo [c][1,2,5]thiadiazole;

2-(5-(2-isobutoxyphenyl)-1H-pyrazol-3-yl)pyridine;

3-(5-(2-isobutoxyphenyl)-1H-pyrazol-3-yl)pyridine;

2-(5-(5-chloro-2-isobutoxyphenyl)-1H-pyrazol-3-yl)pyridine;

3-(5-(5-chloro-2-isobutoxyphenyl)-1H-pyrazol-3-yl)pyridine;

5-(2-methoxy-5-nitrophenyl)-3-phenyl-1H-pyrazole;

3-(5-(2-methoxyphenyl)-1H-pyrazol-3-yl)aniline;

5-(4-(benzyloxy)-2-(2-methoxyethoxy)phenyl)-3-phenyl-1H-pyrazole;

3-(5-(2-methoxyphenyl)-1H-pyrazol-3-yl)pyridine;

4-(5-(5-(2-methoxyphenyl)-1H-pyrazol-3-yl)pyridin-2-yl)morpholine;

5-(1-benzyl-1H-imidazol-2-yl)-3-(3-fluorophenyl)-1H-pyrazole;

3-(5-(1-benzyl-1H-imidazol-2-yl)-1H-pyrazol-3-yl)pyridine;

2-(2-(3-(3-fluorophenyl)-1H-pyrazol-5-yl)phenoxy)-N,N-dimethylacetamide;

N,N-dimethyl-2-(2-(3-(pyridin-3-yl)-1H-pyrazol-5-yl)phenoxy)acetamide;

2-((5-(benzyloxy)-2-(3-phenyl-1H-pyrazol-5-yl)phenoxy)methyl)pyridine;

N-(3-(5-(2-methoxyphenyl)-1H-pyrazol-3-yl)phenyl)acetamide;

N-(3-(5-(2-methoxyphenyl)-1H-pyrazol-3-yl)phenyl)benzamide;

2-(2-(5-(4-cyanophenyl)-1H-pyrazol-3-yl)phenoxy)-N,N-dimethylacetamide;

2-(2-(5-(pyridin-3-yl)-1H-pyrazol-3-yl)phenoxy)-1-(pyrrolidin-1-yl)ethanone;

5-(5-(2-methoxyphenyl)-1H-pyrazol-3-yl)-N,N-dimethylpyridin-2-amine;

5-(3-(3-fluorophenyl)-1H-pyrazol-5-yl)-2,4-dimethoxypyrimidine;

2,4-dimethoxy-5-(3-(pyridin-3-yl)-1H-pyrazol-5-yl)pyrimidine;

3-(2-(3-phenyl-1H-pyrazol-5-yl)phenoxy)pyridine;

2-(3-(3-phenyl-1H-pyrazol-5-yl)phenoxy)pyridine;

5-(2-methoxy-4-nitrophenyl)-3-phenyl-1H-pyrazole;

4-(5-(2-methoxyphenyl)-1H-pyrazol-3-yl)aniline;

3-methoxy-4-(3-phenyl-1H-pyrazol-5-yl)aniline;

5-(2-methoxy-4-(4-methoxybenzyloxy)phenyl)-3-phenyl-1H-pyrazole;

N-(3-methoxy-4-(3-phenyl-1H-pyrazol-5-yl)phenyl)benzamide;

N-(3-methoxy-4-(3-phenyl-1H-pyrazol-5-yl)phenyl)-2-phenylacetamide;

2-(2-(3-(3-fluorophenyl)-1H-pyrazol-5-yl)phenoxy)-1-(pyrrolidin-1-yl)ethanone;

4-(5-(2-(2-oxo-2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-pyrazol-3-yl)benzonitrile;

2-(2-(3-(3-fluorophenyl)-1H-pyrazol-5-yl)phenoxy)-N,N-dimethylethanamine;

N-(2,4-dimethoxybenzyl)-5-(5-(2-methoxyphenyl)-1H-pyrazol-3-yl)pyridin-2-amine;

5-(5-(2-methoxyphenyl)-1H-pyrazol-3-yl)pyridin-2-amine;

3-(2-chlorophenyl)-5-(2-methoxyphenyl)-1H-pyrazole;

5-(2-methoxyphenyl)-3-o-tolyl-1H-pyrazole;

3-(2-chloro-6-fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazole;

N-(2-methoxyethyl)-5-(5-(2-methoxyphenyl)-1H-pyrazol-3-yl)pyridin-2-amine;

3-(5-(2-(3-chlorophenoxy)phenyl)-1H-pyrazol-3-yl)pyridine;

2-(2-(3-(pyridin-3-yl)-1H-pyrazol-5-yl)phenoxy)benzonitrile;

5-(6-methoxybenzofuran-5-yl)-3-phenyl-1H-pyrazole;

5-(2-methoxyphenyl)-1H-pyrazole-3-carboxylic acid;

5-(2-methoxyphenyl)-N-(3-methoxyphenyl)-1H-pyrazole-3-carboxamide;

1-((5-(2-methoxyphenyl)-1H-pyrazol-3-yl)methyl)-1H-benzo[d]imidazole;

3-((5-(2-methoxyphenyl)-1H-pyrazol-3-yl)methyl)quinazoline-2,4(1H,3H)-dione;

(5-(4-(benzyloxy)-2-methoxyphenyl)-1H-pyrazol-3-yl)methanamine;

6-methoxy-3-((5-(2-methoxyphenyl)-1H-pyrazol-3-yl)methyl)quinazolin-4(3H)-one;

6-((5-(4-(benzyloxy)-2-methoxyphenyl)-1H-pyrazol-3-yl)methylamino)-3-methylpyrimidine-2,4(1H,3H)-dione;

3-methoxy-N-((5-(2-methoxyphenyl)-1H-pyrazol-3-yl)methyl)aniline;

4-methoxy-3-(3-phenyl-1H-pyrazol-5-yl)aniline;

N-benzyl-4-methoxy-3-(3-phenyl-1H-pyrazol-5-yl)aniline;

N-benzyl-3-methoxy-4-(3-phenyl-1H-pyrazol-5-yl)aniline;

2-((5-(4-(benzyloxy)-2-methoxyphenyl)-1H-pyrazol-3-yl)methylamino)-6-fluoroquinazolin-4(3H)-one;

2-((5-(2-methoxyphenyl)-1H-pyrazol-3-yl)methyl)isoindoline-1,3-dione;

N-(4-methoxy-3-(3-phenyl-1H-pyrazol-5-yl)phenyl)benzamide;

N-(4-methoxy-3-(3-phenyl-1H-pyrazol-5-yl)phenyl)benzenesulfonamide;

N-(4-methoxy-3-(3-phenyl-1H-pyrazol-5-yl)phenyl)-2-phenylacetamide;

N-(4-methoxy-3-(3-phenyl-1H-pyrazol-5-yl)phenyl)isonicotinamide;

N-(4-methoxy-3-(3-phenyl-1H-pyrazol-5-yl)phenyl)thiazole-5-carboxamide;

N-(4-methoxy-3-(3-phenyl-1H-pyrazol-5-yl)phenyl)furan-3-carboxamide;

N-(4-methoxy-3-(3-phenyl-1H-pyrazol-5-yl)phenyl)tetrahydrofuran-3-carboxamide;

3-methoxy-5-(2-methoxyphenyl)-1H-pyrazole;

3-ethoxy-5-(2-methoxyphenyl)-1H-pyrazole;

5-(2-methoxyphenyl)-3-propoxy-1H-pyrazole;

3-isopropoxy-5-(2-methoxyphenyl)-1H-pyrazole;

3-sec-butoxy-5-(2-methoxyphenyl)-1H-pyrazole;

3-(cyclopentyloxy)-5-(2-methoxyphenyl)-1H-pyrazole;

5-(2-methoxyphenyl)-3-((tetrahydrofuran-2-yl)methoxy)-1H-pyrazole;

3-(2-methoxyethoxy)-5-(2-methoxyphenyl)-1H-pyrazole;

5-(2-methoxyphenyl)-3-(3-methoxypropoxy)-1H-pyrazole;

2-(5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)-N,N-dimethylethanamine;

3-(5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)-N,N-dimethylpropan-1-amine;

3-(benzyloxy)-5-(2-methoxyphenyl)-1H-pyrazole;

5-(2-methoxyphenyl)-3-phenethoxy-1H-pyrazole;

3-(3-fluorobenzyloxy)-5-(2-methoxyphenyl)-1H-pyrazole;

3-(4-fluorobenzyloxy)-5-(2-methoxyphenyl)-1H-pyrazole;

4-((5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)methyl)benzonitrile;

3-(2,4-difluorobenzyloxy)-5-(2-methoxyphenyl)-1H-pyrazole;

2-((5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)methyl)pyridine;

4-((5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)methyl)pyridine;

5-(2-methoxyphenyl)-3-(thiophen-2-ylmethoxy)-1H-pyrazole;

(S)-5-(2-methoxyphenyl)-3-(1-phenylethoxy)-1H-pyrazole;

N,N-diethyl-2-(5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)ethanamine;

5-(2-methoxyphenyl)-3-(2-(thiophen-3-yl)ethoxy)-1H-pyrazole;

1-(3-(5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)propyl)pyrrolidin-2-one;

1-(2-(5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)ethyl)imidazolidin-2-one;

2-(5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)-1-phenylethanone;

5-(2-(5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)ethyl)-4-methylthiazole;

2-((5-(2-methoxyphenyl)-1H-pyrazol-3-yloxy)methyl)thiazole;

5-(2-methoxyphenyl)-3-((1-methyl-1H-imidazol-5-yl)methoxy)-1H-pyrazole; and

5-(2-methoxyphenyl)-3-((1-methyl-1H-imidazol-2-yl)methoxy)-1H-pyrazole.

112. The compound according to claim 111, wherein the compound is in the form of a pharmaceutically acceptable salt.

124. A process comprising:

reacting a compound comprising the formula

with hydrazinecarbothioamide under conditions that form a first reaction product comprising the formula

treating the first reaction product under conditions that form a second reaction product comprising the formula

and

reacting the second reaction product with a compound comprising the formula R₂-L₁-X under conditions that form a product comprising the formula

wherein

X and R_a are each independently a leaving group;

n is selected from the group consisting of 0, 1, 2, 3, 4 and 5;

A is a ring selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted;

L₁ is absent or a linker providing 1, 2, 3, 4 or 5 atom separation between R₂ and the atom to which L₁ is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur;

R₁ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted, or two R₁ are taken together to form a ring; and

R₂ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted.

125. A process comprising:

treating a compound comprising the formula

under conditions that form a first reaction product comprising the formula

reacting the first reaction product with a compound comprising the formula R_cO₂C—

C(R₃)H—

CO₂K under conditions that form a second reaction product comprising the formula

treating the second reaction product under conditions that form a third reaction product comprising the formula

and

reacting the third reaction product with a compound comprising the formula R₂-L₁-OH under conditions that form a product comprising the formula

wherein

R_b and R_c are each independently a (C_1-5)alkyl;

n is selected from the group consisting of 0, 1, 2, 3, 4 and 5;

A is a ring selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted;

L₁ is absent or a linker providing 1, 2, 3, 4 or 5 atom separation between R₂ and the atom to which L₁ is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur;

R₁ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted, or two R₁ are taken together to form a ring;

R₂ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted; and

R₃ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted.

126. A process comprising:

reacting a compound comprising the formula

with a compound comprising the formula (CO₂R_d)₂ under conditions that form a first reaction product comprising the formula

treating the first reaction product under conditions that form a second reaction product comprising the formula

treating the second reaction product under conditions that form a third reaction product comprising the formula

and

reacting the third reaction product with a compound comprising the formula R₂—

OH under conditions that form a product comprising the formula

wherein

R_d is a leaving group;

n is selected from the group consisting of 0, 1, 2, 3, 4 and 5;

A is a ring selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted;

R₁ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted, or two R₁ are taken together to form a ring;

R₂ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted; and

R₃ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted.

127. A process comprising:

reacting a compound comprising the formula

with a compound comprising the formula R₂-L-CO₂R_e under conditions that form a first reaction product comprising the formula

and

treating the first reaction product under conditions that form a product comprising the formula

wherein

R_e is a (C_1-5)alkyl;

n is selected from the group consisting of 0, 1, 2, 3, 4 and 5;

A is a ring selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted;

L is absent or a linker providing 1, 2, 3, 4, 5 or 6 atom separation between R₂ and the ring to which L is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur;

R₁ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted, or two R₁ are taken together to form a ring;

R₂ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted; and

R₃ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted.

128. A process comprising:

reacting a compound comprising the formula

with a compound comprising the formula

R₃LR₂

under conditions that form a product comprising the formula

wherein

n is selected from the group consisting of 0, 1, 2, 3, 4 and 5;

A is a ring selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted;

L is absent or a linker providing 1, 2, 3, 4, 5 or 6 atom separation between R₂ and the ring to which L is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur;

R₁ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted, or two R₁ are taken together to form a ring;

R₂ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted; and

R₃ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted.

129. A process comprising:

reacting a compound comprising the formula

with a compound comprising the formula

under conditions that form a product comprising the formula

wherein

n is selected from the group consisting of 0, 1, 2, 3, 4 and 5;

A is a ring selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted;

L is absent or a linker providing 1, 2, 3, 4, 5 or 6 atom separation between R₂ and the ring to which L is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur;

R₁ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted, or two R₁ are taken together to form a ring; and

R₂ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted; and

130. A process comprising:

treating a compound comprising the formula

under conditions that form a first reaction product comprising the formula

reacting the first reaction product with a compound comprising the formula HNR₅R₆ under conditions that form a product comprising the formula

wherein

n is selected from the group consisting of 0, 1, 2, 3, 4 and 5;

q is selected from the group consisting of 0, 1, 2, 3, 4 and 5;

R_f is a (C_1-5)alkyl;

A is a ring selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted;

R₁ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted, or two R₁ are taken together to form a ring; and

R₅ and R₆ are each independently selected from the group consisting of hydrogen, oxy, hydroxy, carbonyloxy, (C_1-10)alkoxy, (C_4-12)aryloxy, hetero(C_1-10)aryloxy, carbonyl, oxycarbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, hydroxy(C_1-10)alkyl, carbonyl(C_1-10)alkyl, thiocarbonyl(C_1-10)alkyl, sulfonyl(C_1-10)alkyl, sulfinyl(C_1-10)alkyl, (C_1-10)azaalkyl, imino(C_1-10)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-10)alkyl, aryl(C_1-10)alkyl, hetero(C_1-10)aryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, hetero(C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, (C_4-12)aryl, hetero(C_1-10)aryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted, or R₅ and R₆ are taken together to form a substituted or unsubstituted ring.

131. A process comprising:

treating a compound comprising the formula

under conditions that form a first reaction product comprising the formula

and

reacting the first reaction product with a compound comprising Q-OH under conditions that form a product comprising the formula

wherein

R_g is a leaving group;

Q is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, (C_4-12)aryl, hetero(C_1-10)aryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted;

n is selected from the group consisting of 0, 1, 2, 3, 4 and 5;

A is a ring selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted;

L₁ is absent or a linker providing 1, 2, 3, 4 or 5 atom separation between R₂ and the atom to which L₁ is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur;

R₁ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted, or two R₁ are taken together to form a ring;

R₂ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted.

132. A process comprising:

reacting a compound comprising the formula

with a compound comprising the formula

under conditions that form a product comprising the formula

wherein

R_h and R_i are each independently a leaving group;

n is selected from the group consisting of 0, 1, 2, 3, 4 and 5;

A is a ring selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted;

L is absent or a linker providing 1, 2, 3, 4, 5 or 6 atom separation between R₂ and the ring to which L is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur;

R₁ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted, or two R₁ are taken together to form a ring;

R₂ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted; and

R₃ is selected from the group consisting of hydrogen, halo, nitro, cyano, thio, oxy, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl, amino, (C_1-10)alkylamino, sulfonamido, imino, sulfonyl, sulfinyl, (C_1-10)alkyl, halo(C_1-10)alkyl, carbonyl(C_1-3)alkyl, thiocarbonyl(C_1-3)alkyl, sulfonyl(C_1-3)alkyl, sulfinyl(C_1-3)alkyl, amino(C_1-10)alkyl, imino(C_1-3)alkyl, (C_3-12)cycloalkyl(C_1-5)alkyl, hetero(C_3-12)cycloalkyl(C_1-5)alkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl(C_1-5)alkyl, hetero(C_8-12)bicycloaryl(C_1-5)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, (C_9-12)bicycloalkyl, hetero(C_3-12)bicycloalkyl, aryl, heteroaryl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted.

133. A compound comprising the formula

134. A compound comprising the formula

135. A compound comprising the formula

136. A compound comprising the formula

137. A compound comprising the formula

138. A compound comprising the formula

139. A compound comprising the formula

140. A compound comprising the formula

141. A compound comprising the formula

142. A compound comprising the formula

143. A compound comprising the formula