Deacetylase inhibitors and uses thereof
AssigneesPresident and Fellows of Harvard College, Dana-Farber Cancer Institute, Inc.
InventorsWeiping Tang, James E. Bradner, Stuart L. Schreiber
Life of this patent
Estimating the term…
Abstract
The present invention provides novel compounds of formula (I) and pharmaceutical compositions thereof. The inventive compounds are useful as deacetylase inhibitors (e.g., histone deacetylase inhibitors) and may be useful in the treatment of proliferative diseases such as cancer. In particular, the inventive compounds are HDAC6 inhibitors. The invention also provide synthetic methods for preparing the inventive compounds.
Claims24
A method of treating a histone deacetylase-associated cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I):
- or a pharmaceutically acceptable form thereof;
- wherein:
- n is an integer between 1 and 10, inclusive;
- m is an integer between 0 and 5, inclusive;
- k is an integer between 0 and 5, inclusive;
- p is an integer between 0 and 5, inclusive;
- R2 is an optionally substituted acyl moiety;
- R3 is hydrogen;
- halogen;
- cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
- cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
- substituted or unsubstituted, branched or unbranched acyl;
- substituted or unsubstituted, branched or unbranched aryl;
- substituted or unsubstituted, branched or unbranched heteroaryl;
- —ORC;
- —C(═O)RC;
- —CO2RC;
- —CN;
- —SCN;
- —SRC;
- —SORC;
- —SO2RC;
- —NO2;
- —N(RC)2;
- —NHC(═O)RC;
- or —C(RC)3;
- wherein each occurrence of RC is independently hydrogen;
- a protecting group;
- an aliphatic moiety;
- a heteroaliphatic moiety;
- an acyl moiety;
- an aryl moiety;
- a heteroaryl moiety;
- alkoxy;
- aryloxy;
- alkylthio;
- arylthio;
- amino;
- alkylamino;
- dialkylamino;
- heteroaryloxy;
- or a heteroarylthio moiety;
- R4 is hydrogen;
- halogen;
- cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
- cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
- substituted or unsubstituted, branched or unbranched acyl;
- substituted or unsubstituted, branched or unbranched aryl;
- substituted or unsubstituted, branched or unbranched heteroaryl;
- —ORD;
- —C(═O)RD;
- —CO2RD;
- —CN;
- —SCN;
- —SRD;
- —SORD;
- —SO2RD;
- —NO2;
- —N(RD)2;
- —NHC(═O)RD;
- or —C(RD)3;
- wherein each occurrence of RD is independently hydrogen;
- a protecting group;
- an aliphatic moiety;
- a heteroaliphatic moiety;
- an acyl moiety;
- an aryl moiety;
- a heteroaryl moiety;
- alkoxy;
- aryloxy;
- alkylthio;
- arylthio;
- amino;
- alkylamino;
- dialkylamino;
- heteroaryloxy;
- or a heteroarylthio moiety;
- R5 is hydrogen;
- halogen;
- cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
- cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
- substituted or unsubstituted, branched or unbranched acyl;
- substituted or unsubstituted, branched or unbranched aryl;
- substituted or unsubstituted, branched or unbranched heteroaryl;
- —ORE;
- —C(═O)RE;
- —CO2RE;
- —CN;
- —SCN;
- —SRE;
- —SORE;
- —SO2RE;
- —NO2;
- —N(RE)2;
- —NHC(═O)RE;
- or —C(RE)3;
- wherein each occurrence of RE is independently hydrogen;
- a protecting group;
- an aliphatic moiety;
- a heteroaliphatic moiety;
- an acyl moiety;
- an aryl moiety;
- a heteroaryl moiety;
- alkoxy;
- aryloxy;
- alkylthio;
- arylthio;
- amino;
- alkylamino;
- dialkylamino;
- heteroaryloxy;
- or a heteroarylthio moiety;
- and
- wherein the histone deacetylase-associated cancer is selected from the group consisting of leukemia, multiple myeloma, lymphoma, and skin cancer.
Dependencies are inferred from the claim text.