Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors

  • Bioorg Med Chem Lett. 2007 Sep 1;17(17):4895-900. doi: 10.1016/j.bmcl.2007.06.038.
Shoukou Lee  1 ,  Chihiro Shinji ,  Kiyoshi Ogura ,  Motomu Shimizu ,  Satoko Maeda ,  Mayumi Sato ,  Minoru Yoshida ,  Yuichi Hashimoto ,  Hiroyuki Miyachi
Affiliations
  • 1. Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Tokyo, Japan.
PMID: 17588744 DOI: 10.1016/j.bmcl.2007.06.038
Abstract

We designed and synthesized hydroxamic acid derivatives bearing a 4-(3-pyridyl)phenyl group as a cap structure, and found that they exhibit potent histone deacetylase (HDAC) inhibitory activity. A representative compound, 17a, showed more potent growth-inhibitory activity against pancreatic Cancer cells and greater upregulation of p21(WAF1/CIP1) expression than the clinically used HDAC Inhibitor suberoylanilide hydroxamic acid (Zolinza).