Discovery of carbazole carboxamides as novel RORγt inverse agonists.
Eur J Med Chem
; 148: 465-476, 2018 Mar 25.
Article
en 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carbazoles
/
Agonismo Inverso de Drogas
/
Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares
Límite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Año:
2018
Tipo del documento:
Article
País de afiliación:
China