| Autor: |
MacPherson LJ; Research Department, Novartis Pharmaceuticals, Summit, New Jersey 07901, USA., Bayburt EK, Capparelli MP, Carroll BJ, Goldstein R, Justice MR, Zhu L, Hu S, Melton RA, Fryer L, Goldberg RL, Doughty JR, Spirito S, Blancuzzi V, Wilson D, O'Byrne EM, Ganu V, Parker DT |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 1997 Aug 01; Vol. 40 (16), pp. 2525-32. |
| DOI: |
10.1021/jm960871c |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
