Discovery of SAR184841, a potent and long-lasting inhibitor of 11ß-hydroxysteroid dehydrogenase type 1, active in a physiopathological animal model of T2D.
Bioorg Med Chem Lett
; 23(8): 2414-21, 2013 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-23478147
ABSTRACT
Starting from 11ß-HSD1 inhibitors that were active ex vivo but with Cyp 3A4 liability, we obtained a new series of adamantane ureas displaying potent inhibition of both human and rodent 11ß-HSD1 enzymes, devoid of Cyp 3A4 interactions, and rationally designed to provide long-lasting inhibition in target tissues. Final optimizations lead to SAR184841 with good oral pharmacokinetic properties showing in vivo activity and improvement of metabolic parameters in a physiopathological model of type 2 diabetes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Adamantano
/
11-beta-Hidroxiesteroide Desidrogenase Tipo 1
/
Diabetes Mellitus Experimental
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Diabetes Mellitus Tipo 2
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
França