Formylchromone derivatives as a novel class of protein tyrosine phosphatase 1B inhibitors

Formylchromone inhibits a human protein tyrosine phosphatase PTP1B with a IC50 value of 73 muM. The chemical reactivity of formylchromone was adjusted by substitution at various positions of the formylchromone skeleton. In an initial assessment of the structure-activity relationship, the most potent inhibitor showed an IC50 of 4.3 muM against PTP1B and strong or medium selectivity against other human PTPases, LAR and TC-PTP. This compound, however, was not selective against microbial PTPases. YPTP1 and YOP. The potency and selectivity of the formylchromone derivatives expecting further improvements provides a novel pharmacophore for the design of drugs for the treatmenrt of type 2 diabetes and obesity. (C) 2003 Elsevier Ltd. All rights reserved.