SELECTIVE HISTONE DEACETYLASE 8 INHIBITORS

摘要

Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of histone deacetylase 8 (HDAC8). Also described herein are methods of using such HDAC8 inhibitors, alone and in combination with other compounds, for treating diseases or conditions that benefit from inhibition of HDAC8 activity

主权项

1. A compound of formula (I): wherein: R1 is optionally substituted linear or branched alkyl, optionally substituted linear or branched alkenyl, optionally substituted linear or branched alkynyl, optionally substituted cyclyl, optionally substituted heterocyclcyl, optionally substituted aryl, optionally substituted heteroaryl, halogen, CN, CF3, C(O)R5, CO2R5, C(O)N(R6)2, OR5, SR5, SOR5, SO2R5, SSR5N(R6)2, NHR6, NR6C(O)R5, or NO2, each of which can be optionally substituted, wherein the backbone of alkyl, alkenyl, or alkynyl optionally comprises one or more heteroatoms, and wherein the carbon to which R1 is attached has the S stereochemistry; R2 is optionally substituted linear or branched alkyl, optionally substituted linear or branched alkenyl, optionally substituted linear or branched alkynyl, optionally substituted cyclyl, optionally substituted heterocyclcyl, optionally substituted aryl, optionally substituted heteroaryl, halogen, CN, CF3, C(O)R5, CO2R5, C(O)N(R6)2, OR5, SR5, SOR5, SO2R5, OSO2R5, SSR5, N(R6)2, NHR6, NR6C(O)R5, or NO2, each of which can be optionally substituted, and wherein the backbone of alkyl, alkenyl, or alkynyl optionally comprises one or more heteroatoms; R3 is H, optionally substituted linear or branched alkyl, optionally substituted linear or branched alkenyl, optionally substituted linear or branched alkynyl, optionally substituted cyclyl, optionally substituted heterocyclcyl, or optionally substituted aryl, optionally substituted heteroaryl; R4 is a substituent capable of complexing with a histone deacetylase (HDAC) catalytic site or a metal ion, provided that R4 is not an ester, CO2H, or methyl hydroxamide; R5 is independently for each occurrence H, optionally substituted linear or branched alkyl, optionally substituted linear or branched alkenyl, optionally substituted linear or branched alkynyl, optionally substituted cyclyl, optionally substituted heterocyclcyl, optionally substituted aryl, optionally substituted heteroaryl, wherein the backbone of alkyl, alkenyl, or alkynyl optionally comprises one or more heteroatoms; R6 is independently for each occurrence H, optionally substituted linear or branched alkyl, optionally substituted linear or branched alkenyl, optionally substituted linear or branched alkynyl, optionally substituted cyclyl, optionally substituted heterocyclcyl, optionally substituted aryl, optionally substituted heteroaryl, C(O)R5, CO2R5, or SO2R5, each of which can be optionally substituted, wherein the backbone of alkyl, alkenyl, or alkynyl optionally comprises one or more heteroatoms; and a hydrate, salt, solvate, or ester thereof.