Synthesis and PTP1B Inhibition of Novel 4-Aryl-1-Oxa-9-Thiacyclopenta[b]fluorenes

Novel 4-aryl-1-oxa-9-thiacyclopenta[b]fluorenes were designed, synthesized, and evaluated as inhibitors of the protein tyrosine phosphatase, PTP1B. Compounds 3 (IC50=284 nM) and 4 (IC50=74 nM), showed nanomolar potency against PTP1B (TRDI(P)YETD(P)Y(P)YRK as substrate). Compound 4 also lowered insulin in the diabetic ob/ob mouse at a dose of 10 mg/kg/day, po.