Bioorganic & Medicinal Chemistry 2007-08-01

5-Arylidene-2,4-thiazolidinediones as inhibitors of protein tyrosine phosphatases.

Rosanna Maccari, Paolo Paoli, Rosaria Ottanà, Michela Jacomelli, Rosella Ciurleo, Giampaolo Manao, Theodora Steindl, Thierry Langer, Maria Gabriella Vigorita, Guido Camici

Index: Bioorg. Med. Chem. 15(15) , 5137-49, (2007)

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Abstract

4-(5-Arylidene-2,4-dioxothiazolidin-3-yl)methylbenzoic acids (2) were synthesized and evaluated in vitro as inhibitors of PTP1B and LMW-PTP, two protein tyrosine phosphatases (PTPs) which act as negative regulators of the metabolic and mitotic signalling of insulin. The synthesis of compounds 2 represents an example of utilizing phosphotyrosine-mimetics to identify effective low molecular weight nonphosphorus inhibitors of PTPs. Several thiazolidinediones 2 exhibited PTP1B inhibitory activity in the low micromolar range with moderate selectivity for human PTP1B and IF1 isoform of human LMW-PTP compared with other related PTPs.