Synthesis and structure-activity relationship of alpha-sulfonylhydroxamic acids as novel, orally active matrix metalloproteinase inhibitors for the treatment of osteoarthritis.
J Med Chem
; 46(12): 2361-75, 2003 Jun 05.
Article
en En
| MEDLINE
| ID: mdl-12773041
ABSTRACT
The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that play a key role in both physiological and pathological tissue degradation. These enzymes are strictly regulated by endogenous inhibitors such as tissue inhibitors of MMPs and alpha(2)-macroglobulins. Overexpression of these enzymes has been implicated in various pathological disorders such as arthritis, tumor metastasis, cardiovascular diseases, and multiple sclerosis. Developing effective small-molecule inhibitors to modulate MMP activity is one approach to treat these degenerative diseases. The present work focuses on the discovery and SAR of novel N-hydroxy-alpha-phenylsulfonylacetamide derivatives, which are potent, selective, and orally active MMP inhibitors.
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Banco de datos:
MEDLINE
Asunto principal:
Inhibidores de Proteasas
/
Sulfonas
/
Inhibidores de la Metaloproteinasa de la Matriz
/
Ácidos Hidroxámicos
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos