Histone deacetylase inhibitors
Compounds that may be used to inhibit histone deacetylase having the formula Z-Q-L-M or Z-L-M wherein M is a substituent capable of complexing with a deacetylase catalytic site and/or a metal ion; L is a substituent providing between 0-10 atoms separation between the M substituent and the remainder of the compound; and Z and Q are as defined herein.
1. A compound consists of a formula selected from the group consisting of
wherein
R 2 , R 3 , R 4 , and R 5 are each independently selected from the group consisting of hydrogen, halo, alkyl, alkoxy, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, amino, thio, cyano, nitro, and a carbonyl group, each substituted or unsubstituted;
R 14 is selected from the group consisting of hydrogen, halo, alkyl, alkoxy, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, amino, a substituted or unsubstituted —C(O)C 1-6 alkyl, acetyl and BOC;
M is selected from the group consisting of trifluoroacetyl (—C(O)—CF 3 ), —NH—P(O)OH—CH 3 , sulfonamides (—SO 2 NH 2 ), hydroxysulfonamides (—SO 2 NHOH), thiols(—SH), and carbonyl groups having the formula —C(O)—R 13 wherein R 13 is hydroxylamino, hydroxyl, amino, alkylamino, and an alkoxy group, each substituted or unsubstituted; and
L is a substituent providing between 2-10 atoms separation between the M substituent and the remainder of the compound, wherein the 2-10 atoms are all carbon atoms.
2. The compound according to claim 1 , wherein the compound consists of a formula selected from the group consisting of
3. The compound according to claim 1 , wherein the compound consists of a formula selected from the group consisting of
4. The compound according to claim 1 , wherein R 14 is hydrogen.
5. The compound according to claim 1 , wherein R 14 is a substituted or unsubstituted C 1-6 alkyl.
6. The compound according to claim 1 , wherein R 14 is a substituted or unsubstituted —C(O)C 1-6 alkyl.
7. The compound according to claim 1 , wherein R 14 is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, butyl, acetyl, and BOC.
8. The compound according to claim 1 , wherein at least one of R 2 , R 3 , R 4 , or R 5 is fluoro.
9. The compound according to claim 1 , wherein M is selected from the group consisting of:
10. The compound according to claim 1 , wherein M is a hydroxamic acid moiety.
11. The compound according to claim 1 , wherein -L-M is
12. A compound of a formula selected from the group consisting of
wherein
R 2 , R 3 , R 4 , and R 5 are each independently selected from the group consisting of hydrogen, halo, alkyl, alkoxy, aryl, heteroaryl, cyano and nitro, each substituted or unsubstituted;
R 14 is selected from the group consisting of hydrogen, halo, alkyl, alkoxy, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, amino, a substituted or unsubstituted —C(O)C 1-6 alkyl, acetyl and BOC;
M is selected from the group consisting of trifluoroacetyl (—C(O)—CF 3 ), —NH—P(O)OH—CH 3 , sulfonamides (—SO 2 NH 2 ), hydroxysulfonamides (—SO 2 NHOH), thiols(—SH), and carbonyl groups having the formula —C(O)—R 13 wherein R 13 is hydroxylamino, hydroxyl, amino, alkylamino, and an alkoxy group, each substituted or unsubstituted; and
L is a substituent providing between 2-10 atoms separation between the M substituent and the remainder of the compound, wherein the 2-10 atoms are all carbon atoms.
13. The compound according to claim 12 , wherein the compound comprises a formula selected from the group consisting of
14. The compound according to claim 12 , wherein the compound consists of a formula selected from the group consisting of
15. The compound according to claim 12 , wherein R 14 is hydrogen.
16. The compound according to claim 12 , wherein R 14 is a substituted or unsubstituted C 1-6 alkyl.
17. The compound according to claim 12 , wherein R 14 is a substituted or unsubstituted —C(O)C 1-6 alkyl.
18. The compound according to claim 12 , wherein R 14 is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, butyl, acetyl, and BOC.
19. The compound according to claim 12 , wherein at least one of R 2 , R 3 , R 4 , or R 5 is fluoro.
20. The compound according to claim 12 , wherein M is selected from the group consisting of:
21. The compound according to claim 12 , wherein M is a hydroxamic acid moiety.
22. The compound according to claim 12 , wherein -L-M is
23. A compound of a formula selected from the group consisting of
wherein
R 2 , R 3 , R 4 , and R 5 are each independently selected from the group consisting of hydrogen, halo, (C 1-10 )alkyl, (C 1-10 )alkoxy, (C 5-12 )aryl, (C 5-12 )heteroaryl, cyano, and nitro, each substituted or unsubstituted;
R 14 is selected from the group consisting of hydrogen, halo, alkyl, alkoxy, aryl, heteroaryl, aminosulfonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aryloxy, heteroaryloxy, arylalkyl, heteroarylalkyl, amino, a substituted or unsubstituted —C(O)C 1-6 alkyl, acetyl and BOC;
M is selected from the group consisting of
and
L is selected from the group consisting of (E) isomer of —CH═CH—, (Z) isomer or —CH═CH—, and mixture of (E) and (Z) isomers —CH═CH—.
24. The compound according to claim 23 , wherein the compound consists of a formula selected from the group consisting of
25. The compound according to claim 23 , wherein the compound consists of a formula selected from the group consisting of
26. The compound according to claim 23 , wherein R 14 is hydrogen.
27. The compound according to claim 23 , wherein R 14 is a substituted or unsubstituted C 1-6 alkyl.
28. The compound according to claim 23 , wherein R 14 is a substituted or unsubstituted —C(O)C 1-6 alkyl.
29. The compound according to claim 23 , wherein R 14 is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, butyl, acetyl, and BOC.
30. The compound according to claim 23 , wherein at least one of R 2 , R 3 , R 4 , or R 5 is fluoro.
31. The compound according to claim 23 , wherein M is a hydroxamic acid moiety.
32. The compound according to claim 23 , wherein -L-M is
33. The compound according to claim 1 , wherein M is
34. The compound according to claim 1 , wherein M is
35. The compound according to claim 1 , wherein M is
36. The compound according to claim 1 , wherein M is
37. The compound according to claim 1 , wherein M is
38. The compound according to claim 1 , wherein M is
39. The compound according to claim 1 , wherein M is
40. The compound according to claim 1 , wherein M is
41. The compound according to claim 1 , wherein M is
42. The compound according to claim 1 , wherein M is
43. The compound according to claim 12 , wherein M is
44. The compound according to claim 12 , wherein M is
45. The compound according to claim 12 , wherein M is
46. The compound according to claim 12 , wherein M is
47. The compound according to claim 12 , wherein M is
48. The compound according to claim 12 , wherein M is
49. The compound according to claim 12 , wherein M is
50. The compound according to claim 12 , wherein M is
51. The compound according to claim 12 , wherein M is
52. The compound according to claim 12 , wherein M is
53. The compound according to claim 12 , wherein M is
54. The compound according to claim 23 , wherein M is
55. The compound according to claim 23 , wherein M is
56. The compound according to claim 23 , wherein M is
57. The compound according to claim 23 , wherein M is
58. The compound according to claim 23 , wherein M is
59. The compound according to claim 23 , wherein M is
60. The compound according to claim 23 , wherein M is
61. The compound according to claim 23 , wherein M is
62. The compound according to claim 1 , wherein -L-M is
63. The compound according to claim 12 , wherein -L-M is