The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.
The present invention relates to new substituted five-membered compounds and pharmaceutically acceptable salts, esters or prodrugs thereof, compositions of the new compounds together with pharmaceutically acceptable carriers, and uses of the new compounds. The compounds of the invention have the following general formula: ##STR00001##
Histone deacetylase inhibitors and uses thereof are provided that have the general formula: ##STR00001## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, M and L have the definitions as described herein.
Histone deacetylase inhibitors and uses thereof are provided that have the general formula ##STR00001## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are each independently selected from the group consisting of hydrogen, a substituted or unsubstituted straight chained C.sub.1-12 alkyl, C.sub.2-12 aminoalkyl or C.sub.2-12 oxaalkyl, and a substituted and unsubstituted 3, 4, 5, 6, 7 or 8 membered ring, with the proviso that R.sub.3 and R.sub.4 are not both hydrogen; R.sub.5 is selected from the group consisting of a carbonyl, a substituted or unsubstituted C.sub.1-3 alkyl, a substituted or unsubstituted --C.sub.1-3 alkyl-C(O), a substituted or unsubstituted --C(O)--C.sub.1-3 alkyl, and a substituted or unsubstituted --C(O)C(O)C.sub.1-3 alkyl; M is a substituent capable of complexing with a protein metal ion; and L is a substituent comprising a chain of 3 12 atoms connecting the M substituent to the carbon atom alpha to the L substituent.
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.
