Indole amide hydroxamic acids as potent inhibitors of histone deacetylases

  • Bioorg Med Chem Lett. 2003 Jun 2;13(11):1897-901. doi: 10.1016/s0960-894x(03)00301-9.
Yujia Dai  1 ,  Yan Guo ,  Jun Guo ,  Lori J Pease ,  Junling Li ,  Patrick A Marcotte ,  Keith B Glaser ,  Paul Tapang ,  Daniel H Albert ,  Paul L Richardson ,  Steven K Davidsen ,  Michael R Michaelides
Affiliations
  • 1. Cancer Research, Abbott Laboratories, Dept. R47J, Bldg. AP10, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA. [email protected]
PMID: 12749893 DOI: 10.1016/s0960-894x(03)00301-9
Abstract

A series of hydroxamic acid-based HDAC inhibitors with an indole amide residue at the terminus have been synthesized and evaluated. Compounds with a 2-indole amide moiety have been found as the most active inhibitors among the different regioisomers. Introduction of substituents on the indole ring further improved the potency and generated a series of very potent inhibitors with significant antiproliferative activity. A representative compound in the series, 7b, has been found to be orally active in tumor growth inhibition model.