Discovery and structure-activity relationships of novel sulfonamides as potent PTP1B inhibitors.

Research paper by Christopher P CP Holmes, Xianfeng X Li, Yijun Y Pan, Caiding C Xu, Ashok A Bhandari, Claire M CM Moody, Joy A JA Miguel, Steven W SW Ferla, M Nuria MN De Francisco, Brian T BT Frederick, Siqun S Zhou, Natalie N Macher, Larry L Jang, Jennifer D JD Irvine, J Russell JR Grove

Indexed on: 28 Jul '05Published on: 28 Jul '05Published in: Bioorganic & Medicinal Chemistry Letters


A series of novel sulfonamides containing a single difluoromethylene-phosphonate group were discovered to be potent inhibitors of protein tyrosine phosphatase 1B. Structure-activity relationships around the scaffold were investigated, leading to the identification of compounds with IC50 or Ki values in the low nanomolar range. These sulfonamide-based inhibitors exhibit 100 and 30 times higher inhibitory activity than the corresponding tertiary amines and carboxamides, respectively.