Synthesis and biological evaluation of thienopyrimidine derivatives as GPR119 agonists.
Bioorg Med Chem Lett
; 24(17): 4281-5, 2014 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-25082125
ABSTRACT
A series of thienopyrimidine derivatives was synthesized and evaluated for their GPR119 agonistic ability. Several thienopyrimidine derivatives containing R(1) and R(2) substituents displayed potent GPR119 agonistic activity. Among them, compound 5d, which is a prototype, showed good in vitro activity with an EC50 value of 3 nM and human and rat liver microsomal stability. Compound 5d exhibited no CYP inhibition and induction, Herg binding, or mutagenic potential. Compound 5d showed increase insulin secretion in beta TC-6 cell and lowered the glucose excursion in mice in an oral glucose-tolerance test.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
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