Discovery of Novel HDAC Inhibitors by Structure-based Optimization of Cinnamic Hydroxamic Scaffold

A series of di-substituted cinnamic hydroxamic derivatives was designed, synthesized and evaluated as HDAC inhibitors. Compound 5f (HS270) demonstrated potent HDAC inhibitory and antiproliferative activities. In xenograft model, 5f showed significant antitumor efficacy in tumorbearing mice.