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1. (WO2002026696) CARBAMIC ACID COMPOUNDS COMPRISING AN AMIDE LINKAGE AS HDAC INHIBITORS
注意: このテキストは、OCR 処理によってテキスト化されたものです。法的な用途には PDF 版をご利用ください。

CLAIMS

1. A compound of the formula:


wherein:

A is an aryl group;

Q1 is an aryl leader group having a backbone of at least 2 carbon atoms;

J is an amide linkage selected from:


R1 is an amido substituent; and,

Q2 is an acid leader group;

and wherein:

A, is a C5-20aryl group, and is optionally substituted; the aryl leader group is a C1-7alkylene group and is optionally substituted;

the amido substituent, R1, is hydrogen, C1-7alkyl, C3-20heterocyclyl, or C5-20aryl;

the acid leader group, Q2, is C1-7alkylene; C5-20arylene; C5-20arylene-C1-7alkylene; C1-7alkylene-C5-20arylene; and is optionally substituted; and,

the acid leader group, Q2, has a backbone of at least 3 carbon atoms;

and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof.

2. A compound according to claim 1, wherein J is -C(=O)NR1-.

3. A compound according to claim 1, wherein J is -NR1C(=O)-.

4. A compound according to any one of claims 1 to 3, wherein the aryl leader group, Q1, has a backbone of at least 3 carbon atoms.

5. A compound according to any one of claims 1 to 3, wherein the aryl leader group, Q1, has a backbone of at least 4 carbon atoms.

6. A compound according to any one of claims 1 to 3, wherein the aryl leader group, Q1, has a backbone of from 2 to 7 carbon atoms.

7. A compound according to any one of claims 1 to 3, wherein the aryl leader group, Q1, has a backbone of from 3 to 7 carbon atoms.

8. A compound according to any one of claims 1 to 3, wherein the aryl leader group, Q1, has a backbone of 2 carbon atoms.

9. A compound according to any one of claims 1 to 3, wherein the aryl leader group, Q1, has a backbone of 3 carbon atoms.

10. A compound according to any one of claims 1 to 3, wherein the aryl leader group, Q1, has a backbone of 4 carbon atoms.

11. A compound according to any one of claims 1 to 3, wherein the aryl leader group, Q1, has a backbone of 5 carbon atoms.

12. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is a saturated C2-7alkylene group.

13. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is a partially unsaturated C2-7alkylene group.

14. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is an aliphatic C2-7alkylene group.

15. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is a linear C2-7alkylene group.

16. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is a branched C2-7alkylene group.

17. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is an alicyclic C2-7alkylene group.

18. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is a saturated aliphatic C2-7alkylene group.

19. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is a saturated linear C2-7alkylene group.

20. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is a saturated branched C2-7alkylene group.

21. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is a saturated alicyclic C2-7alkylene group.

22. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is a partially unsaturated aliphatic C2-7alkylene group.

23. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is a partially unsaturated linear C2-7alkylene group.

24. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is a partially unsaturated branched C2-7alkylene group.

25. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is a partially unsaturated alicyclic C2-7alkylene group.

26. A compound according to any one of claims 1 to 11, wherein the aryl

leader, Q1 is a partially unsaturated aliphatic C1-7alkylene group with a backbone of at least 2 carbon atoms.

27. A compound according to any one of claims 1 to 11, wherein the aryl

leader, Q1, is a partially unsaturated aliphatic C1-7alkylene group with a backbone of at least 2 carbon atoms, and in Q1, the carbon atom adjacent to J is not saturated.

28. A compound according to any one of claims 1 to 11, wherein the aryl

leader, Q1, is a partially unsaturated aliphatic C1-7alkylene group with a backbone of at least 3 carbon atoms.

29. A compound according to any one of claims 1 to 11, wherein the aryl

leader, the aryl leader, Q1, is a partially unsaturated aliphatic C1-7alkylene group with a backbone of at least 3 carbon atoms, and in Q1, the carbon atom adjacent to J is not saturated.

30. A compound according to any one of claims 1 to 11, wherein the aryl

leader, the aryl leader, Q1, is an unsubstituted partially unsaturated aliphatic C1-7alkylene group with a backbone of at least 2 carbon atoms.

31. A compound according to any one of claims 1 to 11, wherein the aryl

leader, the aryl leader, Q1, is an unsubstituted partially unsaturated aliphatic C1-7alkylene group with a backbone of at least 2 carbon atoms and Q1 is not saturated at the carbon atom adjacent to J.

32. A compound according to any one of claims 1 to 11, wherein the aryl

leader, the aryl leader, Q1, is an unsubstituted partially unsaturated aliphatic C1-7alkylene group with a backbone of at least 3 carbon atoms.

33. A compound according to any one of claims 1 to 11, wherein the aryl leader, the aryl leader, Q1, is an unsubstituted partially unsaturated aliphatic C1-7alkylene group with a backbone of at least 3 carbon atoms and Q1 is not saturated at the carbon atom adjacent to J.

34. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is selected from: -CH=CH-, -CH2CH=CH-, -CH=CH-CH=CH-, and -CH=CHC(CH3)=CH-.

35. A compound according to any one of claims 1 to 11, wherein the aryl leader group, Q1, is selected from: -CH=CH- and -CH=CH-CH=CH-.

36. A compound according to any one of claims 1 to 35, wherein the aryl leader group, Q1, is optionally substituted with one or more groups selected from: halo, hydroxy, ether, C5-20aryl, acyl, amido, and oxo.

37. A compound according to any one of claims 1 to 35, wherein the aryl leader group, Q1, is optionally substituted with one or more groups selected from: - F, -Cl, -Br, -I, -OH, -OMe, -OEt, -OPr, -Ph, and =O.

38. A compound according to any one of claims 1 to 35, wherein the aryl leader group, Q1, is substituted.

39. A compound according to any one of claims 1 to 35, wherein the aryl leader group, Q1, is unsubstituted.

40. A compound according to any one of claims 1 to 39, wherein the acid

leader group, Q2, has a backbone of at least 4 carbon atoms.

41. A compound according to any one of claims 1 to 39, wherein the acid

leader group, Q2, has a backbone of at least 5 carbon atoms.

42. A compound according to any one of claims 1 to 39, wherein the acid leader group, Q2, has a backbone of from 3 to 8 carbon atoms.

43. A compound according to any one of claims 1 to 39, wherein the acid leader group, Q2, has a backbone of from 4 to 8 carbon atoms.

44. A compound according to any one of claims 1 to 39, wherein the acid leader group, Q2, has a backbone of from 5 to 8 carbon atoms.

45. A compound according to any one of claims 1 to 39, wherein the acid leader group, Q2, has a backbone of 4 carbon atoms.

46. A compound according to any one of claims 1 to 39, wherein the acid leader group, Q2, has a backbone of 5 carbon atoms.

47. A compound according to any one of claims 1 to 39, wherein the acid leader group, Q2, has a backbone of 6 carbon atoms.

48. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is a saturated C1-10alkylene group.

49. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is a partially unsaturated C1-10alkylene group.

50. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is an aliphatic C1-10alkylene group.

51. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is a linear C1-10alkylene group.

52. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is a branched C1-10alkylene group.

53. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is an alicyclic C1-10alkylene group.

54. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is a saturated aliphatic C1-10alkylene group.

55. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is a saturated linear C1-10alkylene group.

56. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is a saturated branched C1-10alkylene group.

57. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is a saturated alicyclic C1-10alkylene group.

58. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is a partially unsaturated aliphatic C1-10alkylene group.

59. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is a partially unsaturated linear C1-10alkylene group.

60. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is a partially unsaturated branched C1-10alkylene group.

61. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is a partially unsaturated alicyclic C1-10alkylene group.

62. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is C5-20arylene, and is optionally substituted.

63. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2, is C5-2oarylene-C1-7alkylene or C1-7alkylene-C5-20arylene, and is optionally substituted.

64. A compound according to any one of claims 1 to 47, wherein the acid leader group, Q2 is C5-6arylene-C1-7alkylene or C1-7alkylene-C5-6arylene, and is optionally substituted.

65. A compound according to any one of claims 1 to 47, wherein the acid

leader group, Q2 is phenylene-C1-7alkylene, and is optionally substituted.

66. A compound according to any one of claims 1 to 47, wherein the acid

leader group, Q2 is phenylene-meta-C1-7alkylene or phenylene-para- C1-7alkylene, and is optionally substituted.

67. A compound according to any one of claims 1 to 47, wherein the acid

leader, Q2 has a backbone of at least 4 carbon atoms.

68. A compound according to any one of claims 1 to 47, wherein the acid

leader, Q2 is a C1-10alkylene group with backbone of at least 4 carbon atoms.

69. A compound according to any one of claims 1 to 47, wherein the acid

leader, Q2 is an aliphatic C1-10alkylene group with backbone of at least 4 carbon atoms.

70. A compound according to any one of claims 1 to 47, wherein the acid

leader, Q2 is a linear C1-10alkylene group with backbone of at least 4 carbon atoms.

71. A compound according to any one of claims 1 to 47, wherein the acid

leader, Q2 is a linear saturated C1-10alkylene group with backbone of at least 4 carbon atoms.

72. A compound according to any one of claims 1 to 47, wherein the acid leader, Q2 is a C5-20arylene-C1-7alkylene group, wherein:

(i) said C1-7alkylene moiety does not comprise a carbon-carbon triple bond; or,

(ii) Q2 has a backbone of less than 7 carbon atoms; or,

(iii) both (i) and (ii); or,

(iv) Q2 is unsubstituted phenylene-meta-trans-ethylene.

73. A compound according to any one of claims 1 to 39, wherein the acid

leader group, Q2, is selected from:


74. A compound according to any one of claims 1 to 39, wherein the acid

leader group, Q2, is selected from: -(CH2)4-, -(CH2)5-, and -(CH2)6-.

75. A compound according to any one of claims 1 to 39, wherein the acid

leader group, Q2, is selected from:


76. A compound according to any one of claims 1 to 75, wherein A is

C5-2oheteroaryl or C5-2ocarboaryl, and is optionally substituted.

77. A compound according to any one of claims 1 to 75, wherein A is a

C5-2oaryl group derived from one of the following: benzene, pyridine, furan, indole, pyrrole, imidazole, naphthalene, quinoline, benzimidazole, benzothiofuran, fluorene, acridine, and carbazole.

78. A compound according to any one of claims 1 to 75, wherein A is an optionally substituted phenyl group.

79. A compound according to any one of claims 1 to 75, wherein A is a phenyl group optionally substituted with one or more of the following groups: fluoro, chloro, bromo, iodo, methyl, ethyl, isopropyl, t-butyl, cyano, trifluoromethyl, hydroxy, methoxy, ethoxy, isopropoxy, trifluoromethoxy, phenoxy, methylthio, trifluoromethylthio, hydroxymethyl, amino,

dimethylamino, diethylamino, morpholino, amido, acetamido, acetyl, nitro, sulfonamido, and phenyl.

80. A compound according to any one of claims 1 to 79, wherein the amido substituent, R1, is hydrogen, C1-7alkyl, or C5-20aryl.

81. A compound according to any one of claims 1 to 79, wherein the amido substituent, R1, is hydrogen or C1-7alkyl.

82. A compound according to any one of claims 1 to 79, wherein the amido substituent, R1, is -H, -Me, or -Et.

83. A compound according to any one of claims 1 to 79, wherein the amido substituent, R1, is -H.

174. A composition comprising a compound according to any one of claims 1 to 173 and a pharmaceutically acceptable carrier or diluent.

175. A compound according to any one of claims 1 to 173 for use in a method of treatment of the human or animal body.

176. A compound according to any one of claims 1 to 173 for use in a method of treatment of a condition mediated by HDAC of the human or animal body.

177. A compound according to any one of claims 1 to 173 for use in a method of treatment of a proliferative condition of the human or animal body.

178. A compound according to any one of claims 1 to 173 for use in a method of treatment of cancer of the human or animal body.

179. A compound according to any one of claims 1 to 173 for use in a method of treatment of psoriasis of the human or animal body.

180. Use of a compound according to any one of claims 1 to 173 for the manufacture of a medicament for use in the treatment of a condition mediated by HDAC.

181. Use of a compound according to any one of claims 1 to 173 for the

manufacture of a medicament for use in the treatment of a proliferative condition.

182. Use of a compound according to any one of claims 1 to 173 for the

manufacture of a medicament for use in the treatment of cancer.

183. Use of a compound according to any one of claims 1 to 173 for the

manufacture of a medicament for use in the treatment of psoriasis.

184. A method inhibiting HDAC in a cell comprising said cell with an effective amount of a compound according to any one of claims 1 to 173.

185. A method for the treatment of a condition mediated by HDAC comprising administering to a subject suffering from a condition mediated by HDAC a therapeutically-effective amount of a compound according to any one of claims 1 to 173.

186. A method for the treatment of a proliferative condition comprising

administering to a subject suffering from a proliferative condition a therapeutically-effective amount of a compound according to any one of claims 1 to 173.

187. A method for the treatment of cancer comprising administering to a subject suffering from cancer a therapeutically-effective amount of a compound according to any one of claims 1 to 173.

A method for the treatment of psoriasis comprising administering to a subject suffering from psoriasis a therapeutically-effective amount of a compound according to any one of claims 1 to 173.