Discovery of CGS 27023A, a non-peptidic, potent, and orally active stromelysin inhibitor that blocks cartilage degradation in rabbits

…, MP Capparelli, BJ Carroll, R Goldstein…

Index: MacPherson, Lawrence J.; Bayburt, Erol K.; Capparelli, Michael P.; Carroll, Brian J.; Goldstein, Robert; Justice, Michael R.; Zhu, Lijuan; Hu, Shou-Ih; Melton, Richard A.; Fryer, Lynn; Goldberg, Ron L.; Doughty, John R.; Spirito, Salvatore; Blancuzzi, Vincent; Wilson, Doug; O'Byrne, Elizabeth M.; Ganu, Vishwas; Parker, David T. Journal of Medicinal Chemistry, 1997 , vol. 40, # 16 p. 2525 - 2532

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Citation Number: 332

Abstract

Structure-activity relationships of a lead hydroxamic acid inhibitor of recombinant human stromelysin were systematically defined by taking advantage of a concise synthesis that allowed diverse functionality to be explored at each position in a template. An ex vivo rat model and an in vivo rabbit model of stromelysin-induced cartilage degradation were used to further optimize these analogs for oral activity and duration of action. The culmination of ...