Design of novel and potent cPLA 2 α inhibitors containing an α-methyl-2-ketothiazole as a metabolically stable serine trap

…, G Andrews, M Bernstein, S Connolly, P Hartopp…

Index: Mete, Antonio; Andrews, Glen; Bernstein, Mike; Connolly, Stephen; Hartopp, Paul; Jackson, Clive G.; Lewis, Richard; Martin, Iain; Murray, David; Riley, Rob; Robinson, David H.; Smith, Gill M.; Wells, Edward; Withnall, W. John Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 10 p. 3128 - 3133

Full Text: HTML

Citation Number: 3

Abstract

We report the design of novel, potent cPLA2α inhibitors that possess an α-methyl-2- ketothiazole that acts as a serine-reactive moiety. We describe the optimization of the series for potency and metabolic stability towards ketone reduction. This was achieved by attenuating the reactivity of the ketone using a combination of electronic and steric effects.