Synthesis and biological evaluation of benzocyclobutane-C-glycosides as potent and orally active SGLT1/SGLT2 dual inhibitors.
Bioorg Med Chem Lett
; 28(7): 1182-1187, 2018 04 15.
Article
em En
| MEDLINE
| ID: mdl-29523385
ABSTRACT
Synthesis and biological evaluation of benzocyclobutane-C-glycosides as potent and orally active SGLT1/SGLT2 dual inhibitors are described. Compound 19 showed high inhibitory potency at SGLT1 (IC50â¯=â¯45â¯nM), and excellent potency at SGLT2 (IC50â¯=â¯1â¯nM). It also displayed excellent PK profiles in mice, rats, dogs and monkeys (Fâ¯=â¯78-107%). In SD rats, compound 19 treatments significantly reduced blood glucose levels in a dose-dependent manner. In ZDF rats, compound 19 displayed anti-hyperglycemic effect up to 24â¯h. Therefore, compound 19 may serve as valuable pharmacological tool, and potential use as a treatment for metabolic syndrome.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Derivados de Benzeno
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Ciclobutanos
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Transportador 1 de Glucose-Sódio
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Inibidores do Transportador 2 de Sódio-Glicose
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Glicosídeos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article