Identification of a potent and stable antiproliferative agent by the prodrug formation of a thiolate histone deacetylase inhibitor

  • Bioorg Med Chem Lett. 2007 Mar 15;17(6):1558-61. doi: 10.1016/j.bmcl.2006.12.117.
Takayoshi Suzuki  1 ,  Shinya Hisakawa ,  Yukihiro Itoh ,  Sakiko Maruyama ,  Mineko Kurotaki ,  Hidehiko Nakagawa ,  Naoki Miyata
Affiliations
  • 1. Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. [email protected]
PMID: 17257837 DOI: 10.1016/j.bmcl.2006.12.117
Abstract

To identify prodrugs of a thiolate histone deacetylase inhibitor NCH-31 that show potent antiproliferative activity and are stable in human plasma, we synthesized several candidate prodrugs of NCH-31. Among these compounds, S-2-methyl-3-phenylpropanoyl compound 2 showed more potent antiproliferative activity and higher stability in human plasma than S-isobutyryl compound NCH-51.