N-(2-Amino-phenyl)-4-(heteroarylmethyl)-benzamides as new histone deacetylase inhibitors

Bioorg Med Chem Lett. 2007 Dec 15;17(24):6729-33. doi: 10.1016/j.bmcl.2007.10.050. Epub 2007 Oct 18.

Abstract

A variety of N-(2-amino-phenyl)-4-(heteroarylmethyl)-benzamides were designed and synthesized. These compounds were shown to inhibit recombinant human HDAC1 with IC(50) values in the sub-micromolar range. In human cancer cells growing in culture these compounds induced hyperacetylation of histones, induced the expression of the tumor suppressor protein p21(WAF1/Cip1), and inhibited cellular proliferation. Certain compounds of this class also showed in vivo activity in various human tumor xenograft models in mice.

MeSH terms

  • Amination
  • Animals
  • Benzamides / chemistry*
  • Benzamides / pharmacology*
  • Binding Sites
  • Cell Line
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism
  • Humans
  • Methylation
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Niacin / pharmacology
  • Structure-Activity Relationship
  • Urea / chemistry
  • Vasodilation / drug effects
  • ortho-Aminobenzoates / chemistry

Substances

  • Benzamides
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • ortho-Aminobenzoates
  • anthranilic acid
  • Niacin
  • Urea
  • Histone Deacetylases