Synthesis and biological evaluation of 3-(4-substituted-phenyl)-N-hydroxy-2-propenamides, a new class of histone deacetylase inhibitors

  • J Med Chem. 2003 Dec 18;46(26):5745-51. doi: 10.1021/jm030377q.
Dae-Kee Kim  1 ,  Ju Young Lee ,  Jae-Sun Kim ,  Je-Ho Ryu ,  Jin-Young Choi ,  Jun Won Lee ,  Guang-Jin Im ,  Tae-Kon Kim ,  Jung Woo Seo ,  Hyun-Ju Park ,  Jakyung Yoo ,  Jung-Hyun Park ,  Tae-You Kim ,  Yung-Jue Bang
Affiliations
  • 1. In2Gen Co. Ltd., 28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea. [email protected]
PMID: 14667227 DOI: 10.1021/jm030377q
Abstract

Inhibitors of histone deacetylases (HDACs) have been shown to induce differentiation and/or Apoptosis of human tumor cells. Novel 3-(4-substituted-phenyl)-N-hydroxy-2-propenamides have been prepared as a new class of HDAC inhibitors and evaluated for their antiproliferative activity and HDAC inhibitory activity. Incorporation of a 1,4-phenylene carboxamide linker, shown by 5, and a 4-(dimethylamino)phenyl or 4-(pyrrolidin-1-yl)phenyl group as a cap substructure generated highly potent hydroxamic acid-based HDAC inhibitors 5a and 5b.