Discovery of betamethasone 17alpha-carbamates as dissociated glucocorticoid receptor modulators in the rat.
Bioorg Med Chem
; 16(16): 7535-42, 2008 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-18691892
ABSTRACT
A series of betamethasone 17alpha-carbamates were designed, synthesized, and evaluated for their ability to dissociate the two main functions of the glucocorticoid receptor, that is, transactivation and transrepression, in rat cell lines. A number of alkyl substituted betamethasone 17alpha-carbamates were identified with excellent affinity for the glucocorticoid receptor (e.g., 7, GR IC(50) 5.1 nM) and indicated dissociated profiles in functional assays of transactivation (rat tyrosine aminotransferase, TAT, and rat glutamine synthetase, GS) and transrepression (human A549 cells, MMP-1 assay). Gratifyingly, the in-vivo profile of these compounds, for example, 7, also indicated potent anti-inflammatory activity with impaired effects on glucose, insulin, triglycerides, and body weight. Taken together, these results indicate that dissociated glucocorticoid receptor modulators can be identified in rodents.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Betametasona
/
Carbamatos
/
Receptores de Glucocorticoides
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article