Discovery of CGS 27023A, a Non-Peptidic, Potent, and Orally Active Stromelysin Inhibitor That Blocks Cartilage Degradation in Rabbits
Journal of Medicinal Chemistry1997Vol. 40(16), pp. 2525–2532
Citations Over TimeTop 10% of 1997 papers
Lawrence MacPherson, Erol K. Bayburt, Michael Capparelli, Brian J. Carroll, R Goldstein, Michael R. Justice, Lijuan Zhu, Shou‐Ih Hu, Richard Melton, Lynn R. Fryer, Ron L. Goldberg, John Doughty, S. Spirito, V. Blancuzzi, Doug Wilson, Elizabeth O’Byrne, Vishwas Ganu, David T. Parker
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 these modifications resulted in CGS 27023A, a potent, orally active stromelysin inhibitor that blocks the erosion of cartilage matrix.
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