Design, synthesis, and evaluation of potent, structurally novel peroxisome proliferator-activated receptor (PPAR) delta-selective agonists.
Bioorg Med Chem
; 15(15): 5177-90, 2007 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-17532641
ABSTRACT
A series of 3-(4-alkoxyphenyl)propanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) delta-selective agonists, based on our previously discovered potent human PPARalpha/delta dual agonist TIPP-401 as a lead compound. Structure-activity relationship studies clearly indicated the importance of the chain length of the alkoxy group at the 4-position, and the n-butoxy compound exhibited the most potent PPARdelta transactivation activity and highest PPARdelta selectivity. The (S)-enantiomer of a representative compound exhibited extremely potent PPARdelta transactivation activity, comparable with or somewhat superior to that of the known PPARdelta-selective agonist, GW-501516. The representative compound regulated the expression of genes involved in lipid and glucose homeostasis, and should be useful not only as a chemical tool to study PPARdelta function, but also as a candidate drug for the treatment of metabolic syndrome.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Butiratos
/
PPAR delta
/
Hidrocarbonetos Fluorados
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Japão