5′-Phenyl-3′ H-spiro [indoline-3, 2′-[1, 3, 4] thiadiazol]-2-one inhibitors of ADAMTS-5 (Aggrecanase-2)

…, S Lombardi, KE Georgiadis, E Reifenberg…

Index: Bursavich, Matthew G.; Gilbert, Adam M.; Lombardi, Sabrina; Georgiadis, Katy E.; Reifenberg, Erica; Flannery, Carl R.; Morris, Elisabeth A. Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 20 p. 5630 - 5633

Full Text: HTML

Citation Number: 51

Abstract

5′-Phenyl-3′ H-spiro [indoline-3, 2′-[1, 3, 4] thiadiazol]-2-one inhibitors of ADAMTS-5 (Aggrecanase-2) have been prepared via commercially available starting materials. Selected compounds 23, 33–35 show sub-micromolar ADAMTS-5 potency and strong SAR trends with selectivity over the related metalloproteases ADAMTS-4 (Aggrecanase-1), MMP12, and MMP13. This series of compounds represents progress toward a selective ...