Discovery of carbazole carboxamides as novel RORγt inverse agonists.
Eur J Med Chem
; 148: 465-476, 2018 Mar 25.
Article
em En
| MEDLINE
| ID: mdl-29477887
ABSTRACT
A novel series of carbazole carboxamides was discovered as potent RORγt inverse agonists using a scaffold hybridization strategy. Structure-activity relationship exploration on the amide linker, carbazole ring and arylsulfone moiety of the hybrid amide 3a led to identification of potent RORγt inverse agonists. Compound 6c was found to have a good RORγt activity with an IC50 of 58.5â¯nM in FRET assay, and reasonable inhibitory activity in mouse Th17â¯cell differentiation assay (58.8% inhibition at 0.3⯵M). The binding mode of carbazole carboxamides in RORγt ligand binding domain was discussed.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Carbazóis
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Agonismo Inverso de Drogas
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Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares
Limite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China