Synthesis, in vitro ADME profiling and in vivo pharmacological evaluation of novel glycogen phosphorylase inhibitors.
Bioorg Med Chem Lett
; 30(14): 127117, 2020 07 15.
Article
en En
| MEDLINE
| ID: mdl-32527535
ABSTRACT
A small set of indole-2-carboxamide derivatives identified from a high-throughput screening campaign has been described as a novel, potent, and glucose-sensitive inhibitors of glycogen phosphorylase a (GPa). Among this series of compounds, compound 2 exhibited moderate GP inhibitory activity (IC50 = 0.29 µM), good cellular efficacy (IC50 = 3.24 µM for HepG2 cells and IC50 = 7.15 µM for isolated rat hepatocytes), together with good absorption, distribution, metabolism, and elimination (ADME) profiles. The in vivo animal study revealed that compound 2 significantly inhibited an increase of fasting blood glucose level in adrenaline-induced diabetic mice.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Glucemia
/
Glucógeno Fosforilasa
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Diabetes Mellitus Experimental
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Inhibidores Enzimáticos
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Hipoglucemiantes
/
Indoles
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China