Identification of a series of substituted 2-piperazinyl-5-pyrimidylhydroxamic acids as potent histone deacetylase inhibitors

  • Bioorg Med Chem Lett. 2010 Jan 1;20(1):294-8. doi: 10.1016/j.bmcl.2009.10.118.
Patrick Angibaud  1 ,  Kristof Van Emelen ,  Laurence Decrane ,  Sven van Brandt ,  Peter Ten Holte ,  Isabelle Pilatte ,  Bruno Roux ,  Virginie Poncelet ,  David Speybrouck ,  Laurence Queguiner ,  Sandrine Gaurrand ,  Ann Mariën ,  Wim Floren ,  Lut Janssen ,  Marc Verdonck ,  Jacky van Dun ,  Jacky van Gompel ,  Ron Gilissen ,  Claire Mackie ,  Marc Du Jardin ,  Jozef Peeters ,  Marc Noppe ,  Luc Van Hijfte ,  Eddy Freyne ,  Martin Page ,  Michel Janicot ,  Janine Arts
Affiliations
  • 1. Ortho-Biotech Oncology Research & Development, Department of Medicinal Chemistry, campus de Maigremont BP615, 27106, Val de Reuil, France. [email protected]
PMID: 19906529 DOI: 10.1016/j.bmcl.2009.10.118
Abstract

Pursuing our efforts in designing 5-pyrimidylhydroxamic acid anti-cancer agents, we have identified a new series of potent histone deacetylase (HDAC) inhibitors. These compounds exhibit enzymatic HDAC inhibiting properties with IC(50) values in the nanomolar range and inhibit tumor cell proliferation at similar levels. Good solubility, moderate bioavailability, and promising in vivo activity in xenograft model made this series of compounds interesting starting points to design new potent HDAC inhibitors.