Discovery of orally active sulfonylphenyl thieno[3,2-d]pyrimidine derivatives as GPR119 agonists.
Eur J Med Chem
; 258: 115584, 2023 Oct 05.
Article
em En
| MEDLINE
| ID: mdl-37356344
ABSTRACT
G-protein-coupled receptor 119 (GPR119) has great potential as a therapeutic target for the treatment of type II diabetes. Novel thieno[3,2-d]pyrimidine derivatives were discovered as GPR119 agonists through a bioisosteric replacement strategy. The sulfonylphenyl thieno[3,2-d] pyrimidine scaffold was introduced, and its derivatives exhibited potent agonistic activity for GPR119 in cell-based assays. The representative derivative 43 displayed excellent pharmacokinetic profiles in rodents and significantly improved glucose tolerance in vivo. In OGTT study, compound 43 reduced significantly blood glucose levels in both mice and rats.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article