Histone deacetylase inhibitors
The present invention provides novel HDAC inhibitors and methods of treating diseases using the same.
1 . A compound having the formula:
wherein
Q 1 and Q 2 are independently hydrogen or a moiety having the formula
n is an integer from 1 to 20;
w is an integer from 0 to 1;
x and y are independently integers from 1 to 20;
z is an integer from 0 to 10;
R 1 is a Zn +2 -binding moiety;
R 2 , R 3 , R 4 , and R 5 are independently hydrogen or unsubstituted C 1 -C 6 alkyl;
R 6 is hydrogen or -L 1 -R 10 , wherein
L 1 is a bond, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene, and
R 10 is hydrogen, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted aryl;
R 7 and R 8 are independently hydrogen, —NH 2 , or unsubstituted C 1 -C 6 alkyl;
R 9 is hydrogen or -L 2 -R 11 , wherein
L 2 is a bond, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene, and
R 11 is independently hydrogen, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted aryl;
wherein if z is 0 then Q 1 is not hydrogen, and if Q 1 is hydrogen then at least one Q 2 is not hydrogen and z is an integer from 1 to 10.
2 . The compound of claim 1 , wherein if R 6 and R 10 are hydrogen, then at least one of R 9 or R 11 are not hydrogen, and if R 9 and R 11 are hydrogen, then at least one of R 6 or R 10 are not hydrogen.
3 . The compound of claim 1 , wherein R 1 is —C(O)NHOH, —C(O)OH, —C(O)NH-(2-amino-phenyl), or substituted or unsubstituted tetrazolyl.
4 . The compound of claim 1 , wherein n is an integer from 1 to 5.
5 . The compound of claim 1 , wherein n is an integer from 2 to 5.
6 . The compound of claim 1 , wherein R 2 , R 3 , R 4 , R 5 , R 7 and R 8 are hydrogen.
7 . The compound of claim 1 , wherein w is 1.
8 . The compound of claim 1 , wherein z is an integer from 1 to 2.
9 . The compound of claim 1 , wherein x and y are independently integers from is 2 to 5.
10 . The compound of claim 1 , wherein x and y are independently integers from is 3 to 4.
11 . The compound of claim 1 , wherein x is 3 and y is independently 4.
12 . The compound of claim 1 , wherein R 6 is hydrogen and R 9 is -L 2 -R 11 , wherein
L 2 is substituted or unsubstituted alkylene, and
R 11 is substituted or unsubstituted aryl.
13 . The compound of claim 12 , wherein L 2 is substituted or unsubstituted C 1 -C 5 alkylene.
14 . The compound of claim 12 , wherein L 2 is unsubstituted C 1 -C 8 alkylene or C 1 -C 5 alkylene substituted with substituted or unsubstituted aryl.
15 . The compound of claim 12 , wherein L 2 is unsubstituted C 1 -C 5 alkylene or C 1 -C 5 alkylene substituted with unsubstituted aryl.
16 . The compound of claim 12 , wherein L 2 is —CH 2 —CH 2 —CH(phenyl)-.
17 . The compound of claim 12 , wherein R 11 is unsubstituted aryl or aryl substituted with unsubstituted C 1 -C 10 alkyl, unsubstituted aryl, or —NR 2 R 3 , wherein R 12 and R 13 are independently hydrogen or unsubstituted C 1 -C 10 alkyl.
18 . The compound of claim 1 , wherein only one of Q 1 or Q 2 is not hydrogen.
19 . A method of treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the compound of claim 1 .
20 . A pharmaceutical formulation comprising the compound of claim 1 and a pharmaceutically acceptable excipient.
21 . A method of decreasing the catalytic activity of a histone deacetylase comprising contacting said histone deacetylase with the compound of claim 1 .