Synthesis and Biological Evaluation of 3-(4-Substituted-phenyl)-N-hydroxy-2-propenamides, a New Class of Histone Deacetylase Inhibitors

Inhibitors of histone deacetylases (HDACs) have been shown to induce differentiation and/or apoptosis of human tumor cells. Novel 3-(4-substituted-phenyl)-N-hydroxy-2-propenamides have been prepared as a new class of HDAC inhibitors and evaluated for their antiproliferative activity and HDAC inhibitory activity. Incorporation of a 1,4-phenylene carboxamide linker, shown by <BO>5</BO>, and a 4-(dimethylamino)phenyl or 4-(pyrrolidin-1-yl)phenyl group as a cap substructure generated highly potent hydroxamic acid-based HDAC inhibitors <BO>5a</BO> and <BO>5b</BO>.