Discovery of structurally novel, potent and orally efficacious GPR119 agonists.
Bioorg Med Chem Lett
; 24(10): 2383-7, 2014 May 15.
Article
em En
| MEDLINE
| ID: mdl-24751443
ABSTRACT
Screening hit 5 was identified in a biochemical screen for GPR119 agonists. Compound 5 was structurally novel, displayed modest biochemical activity and no oral exposure, but was structurally distinct from typical GPR119 agonist scaffolds. Systematic optimization led to compound 36 with significantly improved in vitro activity and oral exposure, to elevate GLP1 acutely in an in vivo mouse model at a dose of 10mg/kg.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Pirimidinas
/
Receptores Acoplados a Proteínas G
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2014
Tipo de documento:
Article