Synthesis of isothiazol-3-one derivatives as inhibitors of histone acetyltransferases (HATs)

…, P Workman, M Jarman, E McDonald

Index: Gorsuch, Stephen; Bavetsias, Vassilios; Rowlands, Martin G.; Aherne, G. Wynne; Workman, Paul; Jarman, Michael; McDonald, Edward Bioorganic and Medicinal Chemistry, 2009 , vol. 17, # 2 p. 467 - 474

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Citation Number: 32

Abstract

High-throughput screening led to the identification of isothiazolones 1 and 2 as inhibitors of histone acetyltransferase (HAT) with IC50s of 3μM and 5μM, respectively. Analogues of these hit compounds with variations of the N-phenyl group, and with variety of substituents at C-4, C-5 of the thiazolone ring, were prepared and assayed for inhibition of the HAT enzyme PCAF. Potency is modestly favoured when the N-aryl group is electron deficient (4-pyridyl ...