Diphenylmethylene hydroxamic acids as selective class IIa histone deacetylase inhibitors |
| |
| Authors: | Pierre Tessier David V. Smil Amal Wahhab Silvana Leit Jubrail Rahil Zuomei Li Robert Déziel Jeffrey M. Besterman |
| |
| Affiliation: | 1. MethylGene Inc., Department of Medicinal Chemistry, 7220 Frederick-Banting, Montréal, Québec, Canada H4S 2A1;2. MethylGene Inc., Department of Lead Discovery, 7220 Frederick-Banting, Montréal, Québec, Canada H4S 2A1;3. MethylGene Inc., Department of Molecular Biology, 7220 Frederick-Banting, Montréal, Québec, Canada H4S 2A1 |
| |
| Abstract: | We have identified a series of diphenylmethylene hydroxamic acids as novel and selective HDAC class IIa inhibitors. The original hit, N-hydroxy-2,2-diphenylacetamide (6), has sub-micromolar class IIa HDAC inhibitory activity, while the rigidified oxygen analogue, N-hydroxy-9H-xanthene-9-carboxamide (13), is slightly more selective for HDAC7 with an IC50 of 0.05 μM. Substitution of 6 allows for the modulation of selectivity and potency amongst the class IIa HDAC isotypes. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
