Synthesis and SAR of 1,2,3,4-tetrahydroisoquinolin-1-ones as novel G-protein-coupled receptor 40 (GPR40) antagonists.
Bioorg Med Chem Lett
; 19(9): 2400-3, 2009 May 01.
Article
em En
| MEDLINE
| ID: mdl-19346127
ABSTRACT
The development of a series of novel 1,2,3,4-tetrahydroisoquinolin-1-ones as antagonists of G protein-coupled receptor 40 (GPR40) is described. The synthesis, in vitro inhibitory values for GPR40, in vitro microsomal clearance and rat in vivo clearance data are discussed. Initial hits displayed high rat in vivo clearances that were higher than liver blood flow. Optimization of rat in vivo clearance was achieved and led to the identification of 15i, whose rat oral pharmacokinetic data is reported.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tetra-Hidroisoquinolinas
/
Receptores Acoplados a Proteínas G
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2009
Tipo de documento:
Article