Discovery of novel pyrimidine and malonamide derivatives as TGR5 agonists.
Bioorg Med Chem Lett
; 24(17): 4271-5, 2014 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-25082126
ABSTRACT
Takeda G-protein-coupled receptor 5 (TGR5) is a promising molecular target for metabolic diseases. A series of 4-(2,5-dichlorophenoxy)pyrimidine and cyclopropylmalonamide derivatives were synthesized as potent agonists of TGR5 based on a bioisosteric replacement strategy. Several compounds exhibited improved potency, compared to a reference compound with a pyridine scaffold. The pharmacokinetic profile of the representative compound 18 was considered moderate.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Sistema Enzimático do Citocromo P-450
/
Receptores Acoplados a Proteínas G
/
Descoberta de Drogas
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Inibidores das Enzimas do Citocromo P-450
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Malonatos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2014
Tipo de documento:
Article