| Affiliation: | 1. MethylGene Inc, Department of Medicinal Chemistry, 7220 Frederick-Banting, Montréal, Que., Canada H4S 2A1;2. Department of Molecular Biology, 7220 Frederick-Banting, Montréal, Que., Canada H4S 2A1;3. Department of Lead Discovery, 7220 Frederick-Banting, Montréal, Que., Canada H4S 2A1;4. Department of Protein Biochemistry, 7220 Frederick-Banting, Montréal, Que., Canada H4S 2A1 |
| 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 (IC50 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. |
