| 19111466 |
Smil DV, Manku S, Chantigny YA, Leit S, Wahhab A, Yan TP, Fournel M, Maroun C, Li Z, Lemieux AM, Nicolescu A, Rahil J, Lefebvre S, Panetta A, Besterman JM, Deziel R: Novel HDAC6 isoform selective chiral small molecule histone deacetylase inhibitors. Bioorg Med Chem Lett. 2009 Feb 1;19(3):688-92. Epub 2008 Dec 14.
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. |
32(0,1,1,2) |