Dipeptidyl peptidase inhibitors

• US 20050261271A1
• Filed: 03/15/2005
• Published: 11/24/2005
• Est. Priority Date: 03/15/2004
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda San Diego, Inc. (Takeda Pharmaceutical Company Limited)
• Inventors: Gwaltney, Stephen L., Feng, Jun, Stafford, Jeffrey A., Isbester, Paul K., Salsbury, Jonathon S., Ulysse, Luckner G., Zhang, Zhiyuan, Palmer, Grant J., Elder, Bruce J.
• Granted Patent: US 7,807,689 B2
• Time in Patent Office: Days
• US Class Current: 514/210.200
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• 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 15/16 Masculine contraceptives
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 39/02 Antidotes
• CPC Class Codes: A61P 5/02 of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07D 239/545 : with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C07D 403/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/14 : containing three or more hetero rings

Abstract

Compounds, pharmaceuticals, kits and methods are provided for use with DPP-IV and other S9 proteases that comprise a compound comprising:
wherein M is N or CR₄; Q¹ and Q² are each independently selected from the group consisting of CO, SO, SO₂, and C═NR₉; and each L, X, R₁, R₂, and R₃ are as defined herein.

Claims

1. A compound comprising:

wherein

M is N or CR₄;

Q¹ and Q² are each independently selected from the group consisting of CO, CS, SO, SO₂, and C═

NR₉;

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

R₃ is selected from the group consisting of perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

R₄ is hydrogen or is selected from the group consisting of halo, perhalo(C_1-10)alkyl, amino, cyano, thio, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

R₉ is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted;

L is a linker providing 1, 2 or 3 atom separation between X 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; and

X is selected from the group consisting of (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_4-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

2. The compound according to claim 1, wherein the 1, 2 or 3 atoms of L providing the separation consist of carbon atoms.

3. The compound according to claim 1, wherein the 1, 2 or 3 atoms of L providing the separation are selected from the group of linkers consisting of at least one oxygen or at least one nitrogen atom.

4. The compound according to claim 1, wherein L separates X from the ring atom by one atom.

5. The compound according to claim 1, wherein L is selected from the group consisting of —

CH₂—

, —

CH₂CH₂—

, —

CH₂CH₂CH₂—

, —

C(O)—

, —

CH₂C(O)—

, —

C(O)CH₂—

, —

CH₂—

C(O)CH₂—

, —

C(O)CH₂CH₂—

, —

CH₂CH₂C(O)—

, —

O—

, —

OCH₂—

, —

CH₂O—

, —

CH₂OCH₂—

, —

OCH₂CH₂—

, —

CH₂CH₂O—

, —

N(CH₃)—

, —

NHCH₂—

, —

CH₂NH—

, —

CH₂NHCH₂—

, —

NHCH₂CH₂—

, —

CH₂CH₂NH—

, —

NH—

C(O)—

, —

NCH₃—

C(O)—

, —

C(O)NH—

, —

C(O)NCH₃—

, —

NHC(O)CH₂—

, —

C(O)NHCH₂—

, —

C(O)CH₂NH—

, —

CH₂NHC(O)—

, —

CH₂C(O)NH—

, —

NHCH₂C(O)—

, —

S—

, —

SCH₂—

, —

CH₂S—

, —

SCH₂CH₂—

, —

CH₂SCH₂—

, —

CH₂CH₂S—

, —

C(O)S—

, —

C(O)SCH₂—

, —

CH₂C(O)S—

, —

C(O)CH₂S—

, and —

CH₂SC(O)—

, each substituted or unsubstituted.

6. The compound according to claim 1, wherein L is selected from the group consisting of —

CH₂—

, —

C(O)—

, —

CH₂C(O)—

, —

C(O)CH₂—

, —

CH₂—

C(O)CH₂—

, —

C(O)CH₂CH₂—

, and —

CH₂CH₂C(O)—

, each substituted or unsubstituted.

7. The compound according to claim 1, wherein X is a substituted or unsubstituted (C_3-7)cycloalkyl.

8. The compound according to claim 1, wherein X is a substituted or unsubstituted (C_3-7)heterocycloalkyl.

9. The compound according to claim 1, wherein X is a substituted or unsubstituted aryl.

10. The compound according to claim 1, wherein X is a substituted or unsubstituted phenyl.

11. The compound according to claim 1, wherein X is a substituted or unsubstituted heteroaryl.

12. The compound according to claim 1, wherein X is a ring having a non-hydrogen substituent at a 2 or 3 position of the ring.

13. The compound according to claim 1, wherein X is a ring having a non-hydrogen substituent at a 2 or 3 position of the ring selected from the group consisting of (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_4-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, cyano, nitro, halo, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

14. The compound according to claim 1, wherein X is a substituted or unsubstituted halophenyl or dihalophenyl.

15. The compound according to claim 1, wherein X is a substituted or unsubstituted haloaryl, haloheteroaryl, dihaloaryl or dihaloheteroaryl.

16. The compound according to claim 1, wherein X is selected from the group consisting of (2-cyano)phenyl;

(3-cyano)phenyl;

(2-hydroxy)phenyl;

(3-hydroxy)phenyl;

(2-alkenyl)phenyl;

(3-alkenyl)phenyl;

(2-alkynyl)phenyl;

(3-alkynyl)phenyl;

(2-methoxy)phenyl;

(3-methoxy)phenyl;

(2-nitro)phenyl;

(3-nitro)phenyl;

(2-carboxy)phenyl;

(3-carboxy)phenyl;

—

(CH₂)-(2-carboxamido)phenyl;

(3-carboxamido)phenyl;

(2-sulfonamido)phenyl;

(3-sulfonamido)phenyl;

(2-tetrazolyl)phenyl;

(3-tetrazolyl)phenyl;

(2-aminomethyl)phenyl;

(3-aminomethyl)phenyl;

(2-hydroxymethyl)phenyl;

(3-hydroxymethyl)phenyl;

(2-phenyl)phenyl;

(3-phenyl)phenyl;

(2-halo)phenyl;

(3-halo)phenyl;

(2-CONH₂)phenyl;

(3-CONH₂)phenyl;

(2-CONH(C_1-7)alkyl)phenyl;

(3-CONH(C_1-7)alkyl)phenyl;

(2-CO₂(C_1-7)alkyl)phenyl;

(3-CO₂(C_1-7)alkyl)phenyl;

(2-NH₂)phenyl;

(3-NH₂)phenyl;

(2-(C_3-7)alkyl)phenyl;

(3-(C_3-7)alkyl)phenyl;

(2-(C_3-7)cycloalkyl)phenyl;

(3-(C_3-7)cycloalkyl)phenyl;

(2-aryl)phenyl;

(3-aryl)phenyl;

(2-heteroaryl)phenyl;

(3-heteroaryl)phenyl;

2-bromo-5-fluoro phenyl;

2-chloro-5-fluoro phenyl;

2-cyano-5-fluoro phenyl;

2,5-dichloro phenyl;

2,5-difluoro phenyl;

2,5-dibromo phenyl;

2-bromo-3,5-difluoro phenyl;

2-chloro-3,5-difluoro phenyl;

2,3,5-trifluoro phenyl;

2,3,5,6-tetrafluorophenyl;

2-bromo-3,5,6-trifluoro phenyl;

2-chloro-3,5,6-trifluoro phenyl;

2-cyano-3,5-difluoro phenyl;

2-cyano-3,5,6-trifluoro phenyl;

(2-heterocycloalkyl)phenyl; and

(3-heterocycloalkyl)phenyl, each substituted or unsubstituted.

17. The compound according to claim 1, wherein X is selected from the group consisting of

wherein

A is S, O or NR₂₄;

B is CR₂₃ or N;

R₂₃ is independently selected from the group consisting of hydrogen, halo, perhalo(C_1-10)alkyl, amino, thio, cyano, CF₃, nitro, (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_8-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted; and

R₂₄ is independently selected from the group consisting of hydrogen, perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_8-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted.

18. The compound according to claim 1, wherein X is selected from the group consisting of

wherein

t is 0, 1, 2,3, 4 or 5;

and

each R₇ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, (C_1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

19. The compound according to claim 18, wherein R₇ is independently selected from the group consisting of -cyano, -methoxy, -nitro, -carboxy, -sulfonamido, -tetrazolyl, -aminomethyl, -hydroxymethyl, -phenyl, -halo, —

CONH₂, —

CONH(C_1-7)alkyl, —

CO₂(C_1-7)alkyl, —

NH₂, —

OH, —

(C_1-5)alkyl, -alkenyl, -alkynyl, (C_1-5)cycloalkyl, aryl, heteroaryl, and heterocycloalkyl, each substituted or unsubstituted.

20. The compound according to claim 1, wherein X is selected from the group consisting of

wherein

s is 0, 1, 2, or 3;

and

each R₇ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, (C_1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

21. The compound according to claim 20, wherein R₇ is independently selected from the group consisting of -cyano, -methoxy, -nitro, -carboxy, -sulfonamido, -tetrazolyl, -aminomethyl, -hydroxymethyl, -phenyl, -halo, —

CONH₂, —

CONH(C_1-7)alkyl, —

CO₂(C_1-7)alkyl, —

NH₂, —

OH, —

(C_1-5)alkyl, -alkenyl, -alkynyl, (C_1-5)cycloalkyl, aryl, heteroaryl, and heterocycloalkyl, each substituted or unsubstituted.

22. The compound according to claim 1, wherein R₃ is selected from the group consisting of amino, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, and heteroaryl, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring.

23. The compound according to claim 1, wherein R₃ comprises the formula

wherein R₁₀ and R₁₁ are each independently selected from the group consisting of hydrogen, perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_4-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, and sulfinyl group, each substituted or unsubstituted, or R₁₀ and R₁₁ are taken together to form a 4, 5, 6, or 7 membered ring, each substituted or unsubstituted.

24. The compound according to claim 1, wherein R₃ is a substituted or unsubstituted 3, 4, 5, 6, or 7 membered ring.

25. The compound according to claim 1, wherein R₃ is a substituted or unsubstituted 3, 4, 5, 6, or 7 membered cycloalkyl.

26. The compound according to claim 1, wherein R₃ is a substituted or unsubstituted 4, 5, 6, or 7 membered heterocycloalkyl.

27. The compound according to claim 1, wherein R₃ is a substituted or unsubstituted aryl.

28. The compound according to claim 1, wherein R₃ is a substituted or unsubstituted heteroaryl.

29. The compound according to claim 1, wherein R₃ is selected from the group consisting of

wherein p is 0-12 and each R₈ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, cyano, nitro, hydroxy, alkyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

30. The compound according to claim 29, wherein at least one R₈ comprises a basic nitrogen atom that is capable of interacting with a carboxylic acid side chain of an active site residue of a protein.

31. The compound of claim 30, wherein the basic nitrogen atom forms part of a primary, secondary or tertiary amine.

32. The compound of claim 30, wherein the basic nitrogen atom is a nitrogen ring atom of a heterocycloalkyl comprising a nitrogen ring atom or a heteroaryl comprising a nitrogen ring atom.

33. The compound according to claim 29, wherein at least one R₈ is a primary, secondary or tertiary amine.

34. The compound according to claim 29, wherein at least one R₈ is a substituted or unsubstituted heterocycloalkyl comprising a nitrogen ring atom or a substituted or unsubstituted heteroaryl comprising a nitrogen ring atom.

35. The compound according to claim 29, wherein at least one R₈ is selected from the group consisting of —

NH₂, —

NH(C_1-5 alkyl), —

N(C_1-5 alkyl)₂, piperazine, imidazole, and pyridine.

36. The compound according to claim 1, wherein R₃ is selected from the group consisting of

wherein r is 0-13 and each R₈ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, cyano, nitro, hydroxy, alkyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

37. The compound according to claim 36, wherein at least one R₈ comprises a basic nitrogen atom that is capable of interacting with a carboxylic acid side chain of an active site residue of a protein.

38. The compound of claim 37, wherein the basic nitrogen atom forms part of a primary, secondary or tertiary amine.

39. The compound of claim 37, wherein the basic nitrogen atom is a nitrogen ring atom of a heterocycloalkyl comprising a nitrogen ring atom or a heteroaryl comprising a nitrogen ring atom.

40. The compound according to claim 36, wherein at least one R₈ is a primary, secondary or tertiary amine.

41. The compound according to claim 36, wherein at least one R₈ is a substituted or unsubstituted heterocycloalkyl comprising a nitrogen ring atom or a substituted or unsubstituted heteroaryl comprising a nitrogen ring atom.

42. The compound according to claim 36, wherein at least one R₈ is selected from the group consisting of —

NH₂, —

NH(C_1-5 alkyl), —

N(C_1-5 alkyl)₂, piperazine, imidazole, and pyridine.

43. The compound according to claim 1, wherein R₃ is a substituted or unsubstituted heteroaryl selected from the group consisting of furan, thiophene, pyrrole, pyrazole, triazole, isoxazole, oxazole, thiazole, isothiazole, oxadiazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, benzofuran, isobenzofuran, benzothiophene, isobenzothiophene, imidazole, benzimidazole, indole, isoindole, quinoline, isoquinoline, cinnoline, quinazoline, naphthyridine, pyridopyridine, quinoxaline, phthalazine, and benzothiazole, each substituted or unsubstituted.

44. The compound according to claim 1, wherein R₃ is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted.

45. The compound according to claim 1, wherein R₃ is a substituted or unsubstituted (C_3-7)cycloalkyl ring, optionally comprising O, N(O), N, S, SO, SO₂ or a carbonyl group in the ring.

46. The compound according to claim 1, wherein R₃ is substituted such that R₃ comprises a substituent selected from the group consisting of a primary, secondary or tertiary amine, a heterocycloalkyl comprising a nitrogen ring atom, and a heteroaryl comprising a nitrogen ring atom.

47. The compound according to claim 1, wherein R₃ comprises a basic nitrogen atom that is capable of interacting with a carboxylic acid side chain of an active site residue of a protein.

48. The compound of claim 47, wherein the basic nitrogen of R₃ is separated from the ring atom to which R₃ is attached by between 1-5 atoms.

49. The compound of claim 47, wherein the basic nitrogen atom forms part of a primary, secondary or tertiary amine.

50. The compound of claim 47, wherein the basic nitrogen atom is a nitrogen ring atom of a heterocycloalkyl or a heteroaryl.

51. The compound according to claim 1, wherein R₃ is selected from the group consisting of 3-amino-piperidinyl-1-yl, 3-aminomethyl-pyrrolidin-1-yl, 3-aminoazetidin-1-yl, 3-amino-3-methylpiperidin-1-yl, 3-aminocyclopent-1-yl, 3-aminomethylcyclopent-1-yl, 3-aminomethylcyclohex-1-yl, 3-aminohexahydroazepin-1-yl, 3-amino-cyclohex-1-yl, piperazin-1-yl, homopiperazin-1-yl, 3-amino-pyrrolidin-1-yl, R-3-aminopiperidin-1-yl, R-3-amino-3-methylpiperidin-1-yl, 3-amino-cyclohex-1-yl, 3-amino-cyclopent-1-yl, and 3-amino-pyrrolidin-1-yl, each substituted or unsubstituted.

52. The compound according to claim 1, wherein at least one of Q¹ and Q² is CO.

53. The compound according to claim 1, wherein Q¹ and Q² are CO.

54. The compound according to claim 1, wherein M is nitrogen.

55. The compound according to claim 1, wherein M is CR₄ and where R₄ is selected from the group consisting of

wherein

A is S, O or NR₂₄;

B is CR₂₃ or N;

R₂₃ is independently selected from the group consisting of hydrogen, halo, perhalo(C_1-10)alkyl, amino, thio, cyano, CF₃, nitro, (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_8-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted; and

R₂₄ is independently selected from the group consisting of hydrogen, perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_8-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted.

56. The compound according to claim 1, wherein M is CR₄ and where R₄ is selected from the group consisting of

wherein

u is 0, 1, 2, 3, 4, or 5;

and

each R₁₈ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, (C_1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imine group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

57. The compound according to claim 1, wherein M is CR₄ and where R₄ is selected from the group consisting of

wherein

s is 0, 1, 2, or 3;

and

each R₇ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, (C_1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

58. The compound according to claim 1, wherein R₂ is a substituted or unsubstituted (C_1-10)alkyl.

59. The compound according to claim 1, wherein R₂ is a substituted or unsubstituted (C_1-4)alkyl.

60. The compound according to claim 1, wherein R₂ is —

Y-Z wherein

Y a linker providing 1, 2 or 3 atom separation between Z and the ring to which Y is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur; and

Z is hydrogen or selected from the group consisting of (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_4-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

61. The compound according to claim 1, wherein R₂ is selected from the group consisting of

wherein

A is S, O or NR₂₄;

B is CR₂₃ or N;

R₂₃ is independently selected from the group consisting of hydrogen, halo, perhalo(C_1-10)alkyl, amino, thio, cyano, CF₃, nitro, (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_8-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted; and

R₂₄ is independently selected from the group consisting of hydrogen, perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_8-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted.

62. The compound according to claim 1, wherein R₂ is selected from the group consisting of

wherein

t is 0, 1, 2, 3, 4, or 5;

and

each R₁₈ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, (C_1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imine group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

63. The compound according to claim 1 comprising:

wherein

M is N or CR₄;

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

R₃ is selected from the group consisting of perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

R₄ is hydrogen or is selected from the group consisting of halo, perhalo(C_1-10)alkyl, amino, cyano, thio, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

L is a linker providing 1, 2 or 3 atom separation between X 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; and

X is selected from the group consisting of (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_4-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

64. The compound according to claim 1 comprising:

wherein

n is 1, 2, or 3;

M is N or CR₄;

Q¹ and Q² are each independently selected from the group consisting of CO, CS, SO, SO₂, and C═

NR₉;

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

R₃ is selected from the group consisting of perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

R₄ is hydrogen or is selected from the group consisting of halo, perhalo(C_1-10)alkyl, amino, cyano, thio, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

each R₅ and R₆ is independently hydrogen or is selected from the group consisting of a substituted or unsubstituted (C_1-10)alkyl, a substituted or unsubstituted (C_1-10)alkoxy, cyano, and halo, or where R₅ and R₆ are taken together to form a ring;

R₉ is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted; and

X is selected from the group consisting of (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_4-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

65. The compound according to claim 64, wherein R₅ and R₆ are hydrogen.

66. The compound according to claim 64, wherein R₅ and R₆ are halogen.

67. The compound according to claim 64, wherein R₅ and R₆ are taken together to form a ring.

68. The compound according to claim 64, wherein at least one of R₅ and R₆ is a substituted or unsubstituted —

(C₁-8)alkylene R₁₃, wherein R₁₃ is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_4-12)cycloalkyl, (C₆-12)aryl, hetero(C_5-12)aryl, (C_9-12)bicycloalkyl, hetero(C_9-12)bicycloalkyl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted.

69. The compound according to claim 64, wherein:

n is 1, 2 or 3; and

R₅ and R₆ are hydrogen.

70. The compound according to claim 64, wherein:

n is 1 or 2;

R₃ is selected from the group consisting of amino, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, and a substituted or unsubstituted 4, 5, 6 or 7 membered ring; and

R₅ and R₆ are hydrogen.

71. The compound according to claim 64, wherein:

n is 1, 2 or 3;

R₅ and R₆ are hydrogen; and

R₃ is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted.

72. The compound according to claim 64 comprising:

wherein

m is 0, 1, 2, 3, 4, or 5;

n is 1, 2, or 3;

M is N or CR₄;

Q¹ and Q² are each independently selected from the group consisting of CO, CS, SO, SO₂, and C═

NR₉;

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

R₃ is selected from the group consisting of perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

R₄ is hydrogen or is selected from the group consisting of halo, perhalo(C_1-10)alkyl, amino, cyano, thio, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

each R₅ and R₆ is independently hydrogen or is selected from the group consisting of a substituted or unsubstituted (C_1-10)alkyl, a substituted or unsubstituted (C_1-10)alkoxy, cyano, and halo, or where R₅ and R₆ are taken together to form a ring;

each R₇ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, (C_1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted; and

R₉ is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted.

73. The compound according to claim 72, wherein R₅ and R₆ are hydrogen, m is 1 or 2, and each R₇ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, cyano, nitro, hydroxy, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

74. The compound according to claim 72, wherein:

R₅ and R₆ are hydrogen and R₇ is 2-cyano.

75. The compound of claim 74, wherein n is 1.

76. The compound according to claim 72, wherein:

n is 1, 2 or 3;

R₅ and R₆ are hydrogen; and

each R₇ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, alkenyl, alkynyl, CF₃, cyano, nitro, hydroxy, heteroaryl, aryloxy, heteroaryloxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

77. The compound according to claim 72, wherein:

two R₇ are taken together to form a substituted or unsubstituted fused ring.

78. The compound according to claim 72, wherein:

two R₇ are taken together to form a substituted or unsubstituted bridged ring.

79. The compound according to claim 64 comprising a member selected from the group consisting of:

wherein

n is 1, 2, or 3;

M is N or CR₄;

each of T, U, V, W and Y is independently nitrogen or CR₁₆, provided that no more than two of T, U, V, W and Y are nitrogen;

Q¹ and Q² are each independently selected from the group consisting of CO, CS, SO, SO₂, and C═

NR₉;

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

R₃ is selected from the group consisting of perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

R₄ is hydrogen or is selected from the group consisting of halo, perhalo(C_1-10)alkyl, amino, cyano, thio, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

each R₅ and R₆ is independently hydrogen or is selected from the group consisting of a substituted or unsubstituted (C_1-10)alkyl, a substituted or unsubstituted (C_1-10)alkoxy, cyano, and halo, or where R₅ and R₆ are taken together to form a ring;

R₉ is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted; and

each R₁₆ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, (C_1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

80. The compound according to claim 79, wherein two of T, U, V, W and Y are taken together and substituted through available valencies to form a substituted or unsubstituted ring fused or bridged to the ring formed by T U, V, W and Y.

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

160. The compound according to claim 1, wherein the compound is present in a mixture of stereoisomers.

161. The compound according to claim 1, wherein the compound comprises a single stereoisomer.

81. A compound comprising:

wherein

Q¹ and Q² are each independently selected from the group consisting of CO, CS, SO, SO₂, and C═

NR₉;

R₁ is hydrogen or is selected from the group consisting of halo, perhalo(C_1-10)alkyl, amino, cyano, thio, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

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

R₃ is selected from the group consisting of perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

R₉ is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted;

L is a linker providing 1, 2 or 3 atom separation between X 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; and

X is selected from the group consisting of (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_4-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

82. The compound according to claim 81, wherein the 1, 2 or 3 atoms of L providing the separation consist of carbon atoms.

83. The compound according to claim 81, wherein the 1, 2 or 3 atoms of L providing the separation are selected from the group of linkers consisting of at least one oxygen or at least one nitrogen atom.

84. The compound according to claim 81, wherein L separates X from the ring atom by one atom.

85. The compound according to claim 81, wherein L is selected from the group consisting of —

CH₂—

, —

CH₂CH₂—

, —

CH₂CH₂CH₂—

, —

C(O)—

, —

CH₂C(O)—

, —

C(O)CH₂—

, —

CH₂—

C(O)CH₂—

, —

C(O)CH₂CH₂—

, —

CH₂CH₂C(O)—

, —

O—

, —

OCH₂—

, —

CH₂O—

, —

CH₂OCH₂—

, —

OCH₂CH₂—

, —

CH₂CH₂O—

, —

N(CH₃)—

, —

NHCH₂—

, —

CH₂NH—

, —

CH₂NHCH₂—

, —

NHCH₂CH₂—

, —

CH₂CH₂NH—

, —

NH—

C(O)—

, —

NCH₃—

C(O)—

, —

C(O)NH—

, —

C(O)NCH₃—

, —

NHC(O)CH₂—

, —

C(O)NHCH₂—

, —

C(O)CH₂NH—

, —

CH₂NHC(O)—

, —

CH₂C(O)NH—

, —

NHCH₂C(O)—

, —

S—

, —

SCH₂—

, —

CH₂S—

, —

SCH₂CH₂—

, —

CH₂SCH₂—

, —

CH₂CH₂S—

, —

C(O)S—

, —

C(O)SCH₂—

, —

CH₂C(O)S—

, —

C(O)CH₂S—

, and —

CH₂SC(O)—

, each substituted or unsubstituted.

86. The compound according to claim 81, wherein L is selected from the group consisting of —

CH₂—

, —

C(O)—

, —

CH₂C(O)—

, —

C(O)CH₂—

, —

CH₂—

C(O)CH₂—

, —

C(O)CH₂CH₂—

, and —

CH₂CH₂C(O)—

, each substituted or unsubstituted.

87. The compound according to claim 81, wherein X is a substituted or unsubstituted (C_3-7)cycloalkyl.

88. The compound according to claim 81, wherein X is a substituted or unsubstituted (C_3-7)heterocycloalkyl.

89. The compound according to claim 81, wherein X is a substituted or unsubstituted aryl.

90. The compound according to claim 81, wherein X is a substituted or unsubstituted phenyl.

91. The compound according to claim 81, wherein X is a substituted or unsubstituted heteroaryl.

92. The compound according to claim 81, wherein X is a ring having a non-hydrogen substituent at a 2 or 3 position of the ring.

93. The compound according to claim 81, wherein X is a ring having a non-hydrogen substituent at a 2 or 3 position of the ring selected from the group consisting of (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_4-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, cyano, nitro, halo, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

94. The compound according to claim 81, wherein X is a substituted or unsubstituted halophenyl or dihalophenyl.

95. The compound according to claim 81, wherein X is a substituted or unsubstituted haloaryl, haloheteroaryl, dihaloaryl or dihaloheteroaryl.

96. The compound according to claim 81, wherein X is selected from the group consisting of (2-cyano)phenyl;

(3-cyano)phenyl;

(2-hydroxy)phenyl;

(3-hydroxy)phenyl;

(2-alkenyl)phenyl;

(3-alkenyl)phenyl;

(2-alkynyl)phenyl;

(3-alkynyl)phenyl;

(2-methoxy)phenyl;

(3-methoxy)phenyl;

(2-nitro)phenyl;

(3-nitro)phenyl;

(2-carboxy)phenyl;

(3-carboxy)phenyl;

—

(CH₂)-(2-carboxamido)phenyl;

(3-carboxamido)phenyl;

(2-sulfonamido)phenyl;

(3-sulfonamido)phenyl;

(2-tetrazolyl)phenyl;

(3-tetrazolyl)phenyl;

(2-aminomethyl)phenyl;

(3-aminomethyl)phenyl;

(2-hydroxymethyl)phenyl;

(3-hydroxymethyl)phenyl;

(2-phenyl)phenyl;

(3-phenyl)phenyl;

(2-halo)phenyl;

(3-halo)phenyl;

(2-CONH₂)phenyl;

(3-CONH₂)phenyl;

(2-CONH(C_1-7)alkyl)phenyl;

(3-CONH(C_1-7)alkyl)phenyl;

(2-CO₂(C_1-7)alkyl)phenyl;

(3-CO₂(C_1-7)alkyl)phenyl;

(2-NH₂)phenyl;

(3-NH₂)phenyl;

(2-(C_3-7)alkyl)phenyl;

(3-(C_3-7)alkyl)phenyl;

(2-(C_3-7)cycloalkyl)phenyl;

(3-(C_3-7)cycloalkyl)phenyl;

(2-aryl)phenyl;

(3-aryl)phenyl;

(2-heteroaryl)phenyl;

(3-heteroaryl)phenyl;

2-bromo-5-fluoro phenyl;

2-chloro-5-fluoro phenyl;

2-cyano-5-fluoro phenyl;

2,5-dichloro phenyl;

2,5-difluoro phenyl;

2,5-dibromo phenyl;

2-bromo-3,5-difluoro phenyl;

2-chloro-3,5-difluoro phenyl;

2,3,5-trifluoro phenyl;

2,3,5,6-tetrafluorophenyl;

2-bromo-3,5,6-trifluoro phenyl;

2-chloro-3,5,6-trifluoro phenyl;

2-cyano-3,5-difluoro phenyl;

2-cyano-3,5,6-trifluoro phenyl;

(2-heterocycloalkyl)phenyl; and

(3-heterocycloalkyl)phenyl, each substituted or unsubstituted.

97. The compound according to claim 81, wherein X is selected from the group consisting of

wherein

A is S, O or NR₂₄;

B is CR₂₃ or N;

R₂₃ is independently selected from the group consisting of hydrogen, halo, perhalo(C_1-10)alkyl, amino, thio, cyano, CF₃, nitro, (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_8-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted; and

R₂₄ is independently selected from the group consisting of hydrogen, perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_8-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted.

98. The compound according to claim 81, wherein X is selected from the group consisting of

wherein

t is 0, 1, 2, 3, 4, or 5;

and

each R₇ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, (C_1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

99. The compound according to claim 98, wherein R₇ is independently selected from the group consisting of -cyano, -methoxy, -nitro, -carboxy, -sulfonamido, -tetrazolyl, -aminomethyl, -hydroxymethyl, -phenyl, -halo, —

CONH₂, —

CONH(C_1-7)alkyl, —

CO₂(C_1-7)alkyl, —

NH₂, —

OH, —

(C_1-5)alkyl, -alkenyl, -alkynyl, (C_1-5)cycloalkyl, aryl, heteroaryl, and heterocycloalkyl, each substituted or unsubstituted.

100. A compound according to claim 81, wherein X is selected from the group consisting of

wherein

s is 0, 1, 2, or 3;

and

each R₇ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, (C_1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

101. The compound according to claim 100, wherein R₇ is independently selected from the group consisting of -cyano, -methoxy, -nitro, -carboxy, -sulfonamido, -tetrazolyl, -aminomethyl, -hydroxymethyl, -phenyl, -halo, —

CONH₂, —

CONH(C_1-7)alkyl, —

CO₂(C_1-7)alkyl, —

NH₂, —

OH, —

(C_1-5)alkyl, -alkenyl, -alkynyl, (C_1-5)cycloalkyl, aryl, heteroaryl, and heterocycloalkyl, each substituted or unsubstituted.

102. The compound according to claim 81, wherein R₃ is selected from the group consisting of amino, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, and heteroaryl, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring.

103. The compound according to claim 81, wherein R₃ comprises the formula

wherein R₁₀ and R₁₁ are each independently selected from the group consisting of hydrogen, perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_4-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, sulfonyl group, and sulfinyl group, each substituted or unsubstituted, or R₁₀ and R₁₁ are taken together to form a 4, 5, 6, or 7 membered ring, each substituted or unsubstituted.

104. The compound according to claim 81, wherein R₃ is a substituted or unsubstituted 3, 4, 5, 6, or 7 membered ring.

105. The compound according to claim 81, wherein R₃ is a substituted or unsubstituted 3, 4, 5, 6, or 7 membered cycloalkyl.

106. The compound according to claim 81, wherein R₃ is a substituted or unsubstituted 4, 5, 6, or 7 membered heterocycloalkyl.

107. The compound according to claim 81, wherein R₃ is a substituted or unsubstituted aryl.

108. The compound according to claim 81, wherein R₃ is a substituted or unsubstituted heteroaryl.

109. The compound according to claim 81, wherein R₃ is selected from the group consisting of

wherein p is 0-12 and each R₈ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, cyano, nitro, hydroxy, alkyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

110. The compound according to claim 109, wherein at least one R₈ comprises a basic nitrogen atom that is capable of interacting with a carboxylic acid side chain of an active site residue of a protein.

111. The compound of claim 110, wherein the basic nitrogen atom forms part of a primary, secondary or tertiary amine.

112. The compound of claim 110, wherein the basic nitrogen atom is a nitrogen ring atom of a heterocycloalkyl comprising a nitrogen ring atom or a heteroaryl comprising a nitrogen ring atom.

113. The compound according to claim 109, wherein at least one R₈ is a primary, secondary or tertiary amine.

114. The compound according to claim 109, wherein at least one R₈ is a substituted or unsubstituted heterocycloalkyl comprising a nitrogen ring atom or a substituted or unsubstituted heteroaryl comprising a nitrogen ring atom.

115. The compound according to claim 109, wherein at least one R₈ is selected from the group consisting of —

NH₂, —

NH(C_1-5 alkyl), —

N(C_1-5 alkyl)₂, piperazine, imidazole, and pyridine.

116. The compound according to claim 81, wherein R₃ is selected from the group consisting of

wherein r is 0-13 and each R₈ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, cyano, nitro, hydroxy, alkyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

117. The compound according to claim 116, wherein at least one R₈ comprises a basic nitrogen atom that is capable of interacting with a carboxylic acid side chain of an active site residue of a protein.

118. The compound of claim 117, wherein the basic nitrogen atom forms part of a primary, secondary or tertiary amine.

119. The compound of claim 117, wherein the basic nitrogen atom is a nitrogen ring atom of a heterocycloalkyl comprising a nitrogen ring atom or a heteroaryl comprising a nitrogen ring atom.

120. The compound according to claim 116, wherein at least one R₈ is a primary, secondary or tertiary amine.

121. The compound according to claim 116, wherein at least one R₈ is a substituted or unsubstituted heterocycloalkyl comprising a nitrogen ring atom or a substituted or unsubstituted heteroaryl comprising a nitrogen ring atom.

122. The compound according to claim 116, wherein at least one R₈ is selected from the group consisting of —

NH₂, —

NH(C_1-5 alkyl), —

N(C_1-5 alkyl)₂, piperazine, imidazole, and pyridine.

123. The compound according to claim 81, wherein R₃ is a substituted or unsubstituted heteroaryl selected from the group consisting of furan, thiophene, pyrrole, pyrazole, triazole, isoxazole, oxazole, thiazole, isothiazole, oxadiazole, pyridine, pyridazine, pyrimidine, pyrazine, triazine, benzofuran, isobenzofuran, benzothiophene, isobenzothiophene, imidazole, benzimidazole, indole, isoindole, quinoline, isoquinoline, cinnoline, quinazoline, naphthyridine, pyridopyridine, quinoxaline, phthalazine, and benzothiazole, each substituted or unsubstituted.

124. The compound according to claim 81, wherein R₃ is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted.

125. The compound according to claim 81, wherein R₃ is a substituted or unsubstituted (C_3-7)cycloalkyl ring, optionally comprising O, N(O), N, S, SO, SO₂ or a carbonyl group in the ring.

126. The compound according to claim 81, wherein R₃ is substituted such that R₃ comprises a substituent selected from the group consisting of a primary, secondary or tertiary amine, a heterocycloalkyl comprising a nitrogen ring atom, and a heteroaryl comprising a nitrogen ring atom.

127. The compound according to claim 81, wherein R₃ comprises a basic nitrogen atom that is capable of interacting with a carboxylic acid side chain of an active site residue of a protein.

128. The compound of claim 127, wherein the basic nitrogen of R₃ is separated from the ring atom to which R₃ is attached by between 1-5 atoms.

129. The compound of claim 127, wherein the basic nitrogen atom forms part of a primary, secondary or tertiary amine.

130. The compound of claim 127, wherein the basic nitrogen atom is a nitrogen ring atom of a heterocycloalkyl or a heteroaryl.

131. The compound according to claim 81, wherein R₃ is selected from the group consisting of 3-amino-piperidinyl-1-yl, 3-aminomethyl-pyrrolidin-1-yl, 3-aminoazetidin-1-yl, 3-amino-3-methylpiperidin-1-yl, 3-aminocyclopent-1-yl, 3-aminomethylcyclopent-1-yl, 3-aminomethylcyclohex-1-yl, 3-aminohexahydroazepin-1-yl, 3-amino-cyclohex-1-yl, piperazin-1-yl, homopiperazin-1-yl, 3-amino-pyrrolidin-1-yl, R-3-aminopiperidin-1-yl, R-3-amino-3-methylpiperidin-1-yl, 3-amino-cyclohex-1-yl, 3-amino-cyclopent-1-yl, and 3-amino-pyrrolidin-1-yl, each substituted or unsubstituted.

132. The compound according to claim 81, wherein at least one of Q¹ and Q² is CO.

133. The compound according to claim 81, wherein Q¹ and Q² are CO.

134. The compound according to claim 81, wherein R₂ is a substituted or unsubstituted (C_1-10)alkyl.

135. The compound according to claim 81, wherein R₂ is a substituted or unsubstituted (C_1-4)alkyl.

136. The compound according to claim 81, wherein R₂ is —

Y-Z wherein

Y a linker providing 1, 2 or 3 atom separation between Z and the ring to which Y is attached, wherein the atoms of the linker providing the separation are selected from the group consisting of carbon, oxygen, nitrogen, and sulfur; and

Z is hydrogen or selected from the group consisting of (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_4-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

137. The compound according to claim 81, wherein R₂ is selected from the group consisting of

wherein

A is S, O or NR₂₄;

B is CR₂₃ or N;

R₂₃ is independently selected from the group consisting of hydrogen, halo, perhalo(C_1-10)alkyl, amino, thio, cyano, CF₃, nitro, (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_8-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted; and

R₂₄ is independently selected from the group consisting of hydrogen, perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_8-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, imino group, carbonyl group, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, and sulfinyl group, each substituted or unsubstituted.

138. The compound according to claim 81, wherein R₂ is selected from the group consisting of

wherein

t is 0, 1, 2, 3, 4, or 5;

and

each R₁₈ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, (C_1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imine group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

139. The compound according to claim 81 comprising:

wherein

R₁ is hydrogen or is selected from the group consisting of halo, perhalo(C_1-10)alkyl, amino, cyano, thio, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

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

R₃ is selected from the group consisting of perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

L is a linker providing 1, 2 or 3 atom separation between X 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; and

X is selected from the group consisting of (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_4-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

140. The compound according to claim 81 comprising:

wherein

n is 1, 2, or 3;

Q¹ and Q² are each independently selected from the group consisting of CO, CS, SO, SO₂, and C═

NR₉;

R₁ is hydrogen or is selected from the group consisting of halo, perhalo(C_1-10)alkyl, amino, cyano, thio, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

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

R₃ is selected from the group consisting of perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

each R₅ and R₆ is independently hydrogen or is selected from the group consisting of a substituted or unsubstituted (C_1-10)alkyl, a substituted or unsubstituted (C_1-10)alkoxy, cyano, and halo, or where R₅ and R₆ are taken together to form a ring;

R₉ is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted; and

X is selected from the group consisting of (C_1-10)alkyl, (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl(C_1-5)alkyl, (C_9-12)bicycloaryl, hetero(C_4-12)bicycloaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

141. The compound according to claim 140, wherein R₅ and R₆ are hydrogen.

142. The compound according to claim 140, wherein R₅ and R₆ are halogen.

143. The compound according to claim 140, wherein R₅ and R₆ are taken together to form a ring.

144. The compound according to claim 140, wherein at least one of R₅ and R₆ is a substituted or unsubstituted —

(C₁-8)alkylene R₁₃, wherein R₁₃ is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_4-12)cycloalkyl, (C₆-12)aryl, hetero(C_5-12)aryl, (C_9-12)bicycloalkyl, hetero(C_9-12)bicycloalkyl, (C_9-12)bicycloaryl and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted.

145. The compound according to claim 140, wherein:

n is 1, 2 or 3; and

R₅ and R₆ are hydrogen.

146. The compound according to claim 140, wherein:

n is 1 or 2;

R₃ is selected from the group consisting of amino, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, and a substituted or unsubstituted 4, 5, 6 or 7 membered ring; and

R₅ and R₆ are hydrogen.

147. The compound according to claim 140, wherein:

n is 1, 2 or 3;

R₅ and R₆ are hydrogen; and

R₃ is selected from the group consisting of (C_3-12)cycloalkyl, hetero(C_3-12)cycloalkyl, aryl(C_1-10)alkyl, heteroaryl (C_1-5)alkyl, (C_9-12)bicycloaryl, and hetero(C_4-12)bicycloaryl, each substituted or unsubstituted.

148. The compound according to claim 140 comprising:

wherein

m is 0, 1, 2, 3, 4 or 5;

n is 1, 2, or 3;

Q¹ and Q² are each independently selected from the group consisting of CO, CS, SO, SO₂, and C═

NR₉;

R₁ is hydrogen or is selected from the group consisting of halo, perhalo(C_1-10)alkyl, amino, cyano, thio, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

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

R₃ is selected from the group consisting of perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

each R₅ and R₆ is independently hydrogen or is selected from the group consisting of a substituted or unsubstituted (C_1-10)alkyl, a substituted or unsubstituted (C_1-10)alkoxy, cyano, and halo, or where R₅ and R₆ are taken together to form a ring;

each R₇ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, (C_1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted; and

R₉ is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted.

149. The compound according to claim 148, wherein R₅ and R₆ are hydrogen, m is 1 or 2, and each R₇ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, cyano, nitro, hydroxy, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

150. The compound according to claim 148, wherein:

R₅ and R₆ are hydrogen and R₇ is 2-cyano.

151. The compound of claim 150, wherein n is 1.

152. The compound according to claim 148, wherein:

n is 1, 2 or 3;

R₅ and R₆ are hydrogen; and

each R₇ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, alkenyl, alkynyl, CF₃, cyano, nitro, hydroxy, heteroaryl, aryloxy, heteroaryloxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

153. The compound according to claim 148, wherein:

two R₇ are taken together to form a substituted or unsubstituted fused ring.

154. The compound according to claim 148, wherein:

two R₇ are taken together to form a substituted or unsubstituted bridged ring.

155. The compound according to claim 140 comprising a member selected from the group consisting of:

wherein

n is 1, 2, or 3;

Q¹ and Q² are each independently selected from the group consisting of CO, CS, SO, SO₂, and C═

NR₉;

each of T, U, V, W and Y is independently nitrogen or CR₁₆, provided that no more than two of T, U, V, W and Y are nitrogen;

R₁ is hydrogen or is selected from the group consisting of halo, perhalo(C_1-10)alkyl, amino, cyano, thio, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted;

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

R₃ is selected from the group consisting of perhalo(C_1-10)alkyl, amino, (C_1-10)alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, aryl, heteroaryl, carbonyl (C_1-3)alkyl, thiocarbonyl (C_1-3)alkyl, sulfonyl (C_1-3)alkyl, sulfinyl (C_1-3)alkyl, imino (C_1-3)alkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, and a substituted or unsubstituted 3, 4, 5, 6 or 7 membered ring;

each R₅ and R₆ is independently hydrogen or is selected from the group consisting of a substituted or unsubstituted (C_1-10)alkyl, a substituted or unsubstituted (C_1-10)alkoxy, cyano, and halo, or where R₅ and R₆ are taken together to form a ring;

R₉ is hydrogen or is selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, bicycloaryl, and heterobicycloaryl, each substituted or unsubstituted; and

each R₁₆ is independently selected from the group consisting of halo, perhalo(C_1-10)alkyl, CF₃, (C_1-10)alkyl, alkenyl, alkynyl, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, cycloalkyl, heterocycloalkyl, amino, thio, cyano, nitro, hydroxy, alkoxy, carbonyl group, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.

156. The compound according to claim 155, wherein two of T, U, V, W and Y are taken together and substituted through available valencies to form a substituted or unsubstituted ring fused or bridged to the ring formed by T U, V, W and Y.

157. A compound selected from the group consisting of:

2-(6-Chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl)-benzonitrile;

2-(6-Chloro-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl)-benzonitrile;

2-{6-[3-Amino-piperidin-1-yl]-3-ethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3-Amino-piperidin-1-yl]-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3-Amino-piperidin-1-yl]-5-chloro-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

6-[3-Amino-piperidin-1-yl]-1-(2-bromo-benzyl)-1H-pyrimidine-2,4-dione;

6-[3-Amino-piperidin-1-yl]-1-(2-iodo-benzyl)-1H-pyrimidine-2,4-dione;

6-[3-Amino-piperidin-1-yl]-1-(2-bromo-5-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

6-[3-Amino-piperidin-1-yl]-1-(2-chloro-5-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

6-[3-Amino-piperidin-1-yl]-1-(2-chloro-4-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

6-[3-Amino-piperidin-1-yl]-1-(2-bromo-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

2-{6-[Azepan-3 (±

)-ylamino]-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile (14);

2-{6-[3(±

)-Amino-azepan-1-yl]-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-[6-(2-Amino-ethylamino)-3-ethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-benzonitrile;

2-{6-[3-Amino-piperidin-1-yl]-3-(3-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3-Amino-piperidin-1-yl]-3-(4-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-[6-(3-Amino-piperidin-1-yl)-3-(1H-benzoimidazol-2-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-benzonitrile;

2-{6-[3-Amino-piperidin-1-yl]-2,4-dioxo-3-(4-pyrazol-1-yl-benzyl)-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3-Amino-piperidin-1-yl]-2,4-dioxo-3-(3-pyrrol-1-yl-benzyl)-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

6-[3-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl]-thiophene-3-carbonitrile;

3-{4-[3-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl}-benzoic acid methyl ester;

3-{4-[3-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl}-benzoic acid;

6-[3-Amino-piperidin-1-yl]-1,3-bis-(2-bromo-5-fluoro-benzyl)-1H-pyrimidine-2,4-dione;

2-{6-[3(R)-Amino-piperidin-1-yl]-5-chloro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

6-[3 (R)-Amino-piperidin-1-yl]-1-(2,5-di-chloro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

6-[3 (R)-Amino-piperidin-1-yl]-1-(2-chloro-3,6-di-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione; and

(R)-2-((6-(3-amino-3-methylpiperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1 (2H)-yl)methyl)-4-fluorobenzonitrile.

158. A compound selected from the group consisting of:

2-{6-[3(R)-Amino-piperidin-1-yl]-3-ethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3(R)-Amino-piperidin-1-yl]-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3(R)-Amino-piperidin-1-yl]-5-chloro-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

6-[3 (R)-Amino-piperidin-1-yl]-1-(2-bromo-benzyl)-1H-pyrimidine-2,4-dione;

6-[3 (R)-Amino-piperidin-1-yl]-1-(2-iodo-benzyl)-1H-pyrimidine-2,4-dione;

6-[3 (R)-Amino-piperidin-1-yl]-1-(2-bromo-5-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

6-[3 (R)-Amino-piperidin-1-yl]-1-(2-chloro-5-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

6-[3 (R)-Amino-piperidin-1-yl]-1-(2-chloro-4-fluoro-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

6-[3 (R)-Amino-piperidin-1-yl]-1-(2-bromo-benzyl)-3-methyl-1H-pyrimidine-2,4-dione;

2-{6-[3(R)-Amino-piperidin-1-yl]-3-(3-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3(R)-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3(R)-Amino-piperidin-1-yl]-3-(4-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-[6-(3-Amino-piperidin-1-yl)-3-(1H-benzoimidazol-2-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-benzonitrile 2-{6-[3(R)-Amino-piperidin-1-yl]-2,4-dioxo-3-(4-pyrazol-1-yl-benzyl)-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

2-{6-[3(R)-Amino-piperidin-1-yl]-2,4-dioxo-3-(3-pyrrol-1-yl-benzyl)-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile;

6-[3 (R)-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl]-thiophene-3-carbonitrile;

3-{4-[3(R)-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl}-benzoic acid methyl ester;

3-{4-[3(R)-Amino-piperidin-1-yl]-3-(2-cyano-benzyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl}-benzoic acid; and

6-[3(R)-Amino-piperidin-1-yl]-1,3-bis-(2-bromo-5-fluoro-benzyl)-1H-pyrimidine-2,4-dione.