Synthesis and SAR of diazepine and thiazepine TACE and MMP inhibitors

…, T Cummons, D Barone, S Ayral-Kaloustian…

Index: Zask, Arie; Kaplan, Joshua; Du, XueMei; MacEwan, Gloria; Sandanayaka, Vincent; Eudy, Nancy; Levin, Jeremy; Jin, Guixian; Xu, Jun; Cummons, Terri; Barone, Dauphine; Ayral-Kaloustian, Semiramis; Skotnicki, Jerauld Bioorganic and Medicinal Chemistry Letters, 2005 , vol. 15, # 6 p. 1641 - 1645

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Citation Number: 25

Abstract

Potent and selective TACE and MMP inhibitors utilizing the diazepine and thiazepine ring systems were synthesized and evaluated for biological activity in in vitro and in vivo models of TNF-α release. Oral activity in the mouse LPS model of TNF-α release was seen. Efficacy in the mouse collagen induced arthritis model was achieved with diazepine 20.