2,3-Diarylcyclopentenones as orally active, highly selective cyclooxygenase-2 inhibitors.
J Med Chem
; 42(7): 1274-81, 1999 Apr 08.
Article
em En
| MEDLINE
| ID: mdl-10197970
ABSTRACT
Cyclopentenones containing a 4-(methylsulfonyl)phenyl group in the 3-position and a phenyl ring in the 2-position are selective inhibitors of cyclooxygenase-2 (COX-2). The selectivity for COX-2 over COX-1 is dramatically improved by substituting the 2-phenyl group with halogens in the meta position or by replacing the phenyl ring with a 2- or 3-pyridyl ring. Thus the 3,5-difluorophenyl derivative 7 (L-776,967) and the 3-pyridyl derivative 13 (L-784,506) are particularly interesting as potential antiinflammatory agents with reduced side-effect profiles. Both exhibit good oral bioavailability and are potent in standard models of pain, fever, and inflammation yet have a much reduced effect on the GI integrity of rats compared to standard nonsteroidal antiflammatory drugs.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfonas
/
Inibidores de Ciclo-Oxigenase
/
Prostaglandina-Endoperóxido Sintases
/
Ciclopentanos
/
Isoenzimas
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos