4-(Heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides and their analogs as a novel class of histone deacetylase inhibitors

The synthesis and biological evaluation of a variety of 4-(heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides and their analogs is described. Some of these compounds were shown to inhibit HDAC1 with IC50 values below the micromolar range, induce hyperacetylation of histones, upregulate expression of the tumor suppressor p21WAF1/Cip1, and inhibit proliferation of human cancer cells. In addition, certain compounds of this class were active in several human tumor xenograft models in vivo.

The synthesis and biological evaluation as histone deacetylase (HDAC) inhibitors of a variety of 4-(heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides of general structure 5 is described.Figure optionsDownload as PowerPoint slide