Design and synthesis of 4-[(s-triazin-2-ylamino)methyl]-N-(2-aminophenyl)-benzamides and their analogues as a novel class of histone deacetylase inhibitors.

Inhibition of histone deacetylases (HDAC) is emerging as a new strategy in human cancer therapy. The synthesis and biological evaluation of a variety of 4-(heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides is presented herein. From the different series bearing a six-membered heteroaromatic ring studied, the s-triazine series showed the best HDAC1 enzyme and in vitro anti-proliferative activities with IC(50) values below micromolar range. Some of these compounds can also significantly reduce tumor growth in human tumor xenograft models in mice.

Substituted N-(2-aminophenyl)-benzamides, (E)-N-(2-aminophenyl)-acrylamides and their analogues: novel classes of histone deacetylase inhibitors.

Inhibition of histone deacetylases (HDACs) is emerging as a new strategy in human cancer therapy. Novel 2-aminophenyl benzamides and acrylamides, that can inhibit human HDAC enzymes and induce hyperacetylation of histones in human cancer cells, have been designed and synthesized. These compounds selectively inhibit proliferation and cause cell cycle arrest in various human cancer cells but not in normal cells. The growth inhibition of 2-aminophenyl benzamides and acrylamides against human cancer cells in vitro is reversible and is dependent on the induction of histone acetylation. Compounds of this class can significantly reduce tumor growth in human tumor xenograft models.