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ID: ALA1153913

Journal: Bioorg Med Chem

Title: 5-Arylidene-2-phenylimino-4-thiazolidinones as PTP1B and LMW-PTP inhibitors.

Authors: Ottanà R, Maccari R, Ciurleo R, Paoli P, Jacomelli M, Manao G, Camici G, Laggner C, Langer T.

Abstract: As part of a project aimed at identifying effective low molecular weight nonphosphorus monoanionic inhibitors of PTPs, we have synthesized 4-[(5-arylidene-4-oxo-2-phenyliminothiazolidin-3-yl)methyl]benzoic acids (4) and evaluated their inhibitory activity against human PTP1B and LMW-PTP enzymes. The introduction of a 2-phenylimino moiety onto the 4-thiazolidinone ring was designed to enhance the inhibitor/enzyme affinity by means of further favourable interactions with residues of the active site and the surrounding loops. Some of the compounds (4a-d, f) showed interesting inhibition levels in the low micromolar range. The 5-arylidene moiety of acids 4 proved to markedly influence the potency of these inhibitors. Molecular modeling experiments inside the binding sites of both enzymes were performed.

CiteXplore: 19217304

DOI: 10.1016/j.bmc.2009.01.044