Structure–activity relationships of aryloxyalkanoic acid hydroxyamides as potent inhibitors of histone deacetylase

Syntheses of aryloxyalkanoic acid hydroxyamides are described, all of which are potent inhibitors of histone deacetylase, some being more potent in vitro than trichostatin A (IC50 = 3 nM). Variation of the substituents on the benzene ring as well as fusion of a second ring have marked effects on potency, in vitro IC50 values down to 1 nM being obtained.

Graphical abstractAryl ether inhibitors of histone deacetylase are described.Figure optionsDownload full-size imageDownload as PowerPoint slide