Design and synthesis of a novel and potent series of inhibitors of cytosolic phospholipase A2 based on a 1, 3-disubstituted propan-2-one skeleton

…, K Hardy, P Hartopp, CG Jackson, SJ King…

文献索引：Connolly, Stephen; Bennion, Colin; Botterell, Sarah; Croshaw, Pamela J.; Hallam, Catherine; Hardy, Kim; Hartopp, Paul; Jackson, Clive G.; King, Sarah J.; Lawrence, Louise; Mete, Antonio; Murray, David; Robinson, David H.; Smith, Gillian M.; Stein, Linda; Walters, Iain; Wells, Edward; Withnall, W. John Journal of Medicinal Chemistry, 2002 , vol. 45, # 6 p. 1348 - 1362

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被引用次数: 80

摘要

Using knowledge of the substrate specificity of cPLA2 (phospholipases A2), a novel series of inhibitors of this enzyme were designed based upon a three point model of inhibitor binding to the enzyme active site comprising a lipophilic anchor, an electrophilic serine “trap”, and an acidic binding moiety. The resulting 1, 3-diheteroatom-substituted propan-2-ones were evaluated as inhibitors of cPLA2 in both aggregated bilayer and soluble substrate assays. ...