Aromatic sulfide inhibitors of histone deacetylase based on arylsulfinyl-2,4-hexadienoic acid hydroxyamides

The synthesis of a novel series of potent inhibitors of histone deacetylases is described, based on arylsulfinyl-2,4-hexadienoic acid hydroxyamides and their derivatives. In vitro IC50 values down to 40 nM were obtained, and several compounds showed inhibition of CEM (human leukemic) cell viability with IC50 of similar to 1.5 mu M, comparable to or better than that of suberoylanilide hydroxamic acid, an inhibitor of historic deacetylase currently in clinical trials.