Exploration of the HDAC2 foot pocket: Synthesis and SAR of substituted N-(2-aminophenyl)benzamides

  • Bioorg Med Chem Lett. 2010 May 15;20(10):3142-5. doi: 10.1016/j.bmcl.2010.03.091.
Jerome C Bressi  1 ,  Andy J Jennings ,  Robert Skene ,  Yiqin Wu ,  Robert Melkus ,  Ron De Jong ,  Shawn O'Connell ,  Charles E Grimshaw ,  Marc Navre ,  Anthony R Gangloff
Affiliations
  • 1. Takeda San Diego, San Diego, CA 92121, USA.
PMID: 20392638 DOI: 10.1016/j.bmcl.2010.03.091
Abstract

A series of N-(2-amino-5-substituted phenyl)benzamides (3-21) were designed, synthesized and evaluated for their inhibition of HDAC2 and their cytotoxicity in HCT116 Cancer cells. Multiple compounds from this series demonstrated time-dependent binding kinetics that is rationalized using a co-complex crystal structure of HDAC2 and N-(4-aminobiphenyl-3-yl)benzamide (6).