Novel HDAC6 isoform selective chiral small molecule histone deacetylase inhibitors - PubMed (original) (raw)

. 2009 Feb 1;19(3):688-92.

doi: 10.1016/j.bmcl.2008.12.045. Epub 2008 Dec 14.

Sukhdev Manku, Yves A Chantigny, Silvana Leit, Amal Wahhab, Theresa P Yan, Marielle Fournel, Christiane Maroun, Zuomei Li, Anne-Marie Lemieux, Alina Nicolescu, Jubrail Rahil, Sylvain Lefebvre, Anthony Panetta, Jeffrey M Besterman, Robert Déziel

Affiliations

• PMID: 19111466
• DOI: 10.1016/j.bmcl.2008.12.045

Novel HDAC6 isoform selective chiral small molecule histone deacetylase inhibitors

David V Smil et al. Bioorg Med Chem Lett. 2009.

Abstract

In an effort to identify HDAC isoform selective inhibitors, we designed and synthesized novel, chiral 3,4-dihydroquinoxalin-2(1H)-one and piperazine-2,5-dione aryl hydroxamates showing selectivity (up to 40-fold) for human HDAC6 over other class I/IIa HDACs. The observed selectivity and potency (IC(50) values 10-200 nM against HDAC6) is markedly dependent on the absolute configuration of the chiral moiety, and suggests new possibilities for use of chiral compounds in selective HDAC isoform inhibition.

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