Synthesis and evaluation of 2-Nonylaminopyridine derivatives as PPAR ligands.
Chem Pharm Bull (Tokyo)
; 55(7): 1053-9, 2007 Jul.
Article
en En
| MEDLINE
| ID: mdl-17603200
To find novel PPAR ligands, we prepared several 3-{3 or 4-[2-(nonylpyridin-2-ylamino)ethoxy]phenyl}propanoic acid derivatives which were designed based on the structure of our previous PPARgamma ligand 1. In PPAR binding affinity assays, compound 4, which had an ethoxy group at the C-2 position of the propanoic acid of 1, showed selective binding affinity for PPARgamma. Compound 3, with an ethyl group at the C-2 position, was found to be a PPARalpha/gamma dual ligand. Compound 6, the meta isomer of 1, has been shown to be a PPARalpha ligand. The introduction of methyl (7) and ethyl (8) groups to the C-2 position of the propanoic acid of 6 further improved PPARalpha-binding potency. In cell-based transactivation assay, compounds 3 and 4 showed dual-agonist activity toward PPARalpha and PPARgamma. Compound 6 was found to be a triple agonist and compound 8 proved to be a selective PPARalpha agonist. In the human hypodermic preadipocyte differentiation test, it was demonstrated that the maximal activity of compounds 3 and 4 was higher than that of rosiglitazone.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores Activados del Proliferador del Peroxisoma
/
Aminopiridinas
Límite:
Humans
Idioma:
En
Revista:
Chem Pharm Bull (Tokyo)
Año:
2007
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Japón