Modulation of PPAR receptor subtype selectivity of the ligands: aliphatic chain vs aromatic ring as a spacer between pharmacophore and the lipophilic moiety.
Bioorg Med Chem Lett
; 18(24): 6471-5, 2008 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-18976908
ABSTRACT
Oxazole containing glycine and oximinobutyric acid derivatives were synthesized as PPARalpha agonists by incorporating polymethylene spacer as a replacement of commonly used phenylene group that connects the acidic head with lipophilic tail. Compound 13a was found to be a selective and potent PPARalpha agonist. Further 1,3-dioxane-2-carboxylic acid derivative 20 was synthesized by replacing the tetramethylene spacer of NS-220, a selective PPARalpha agonist with phenylene group and found to exhibit PPARalpha/gamma dual agonism. These results suggest that compounds possessing polymethylene spacer between pharmacophore and lipophilic tail exhibit predominantly PPARalpha agonism whereas those with an aromatic phenylene spacer shows PPARalpha/gamma dual agonism.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Química Farmacêutica
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Receptores Ativados por Proliferador de Peroxissomo
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PPAR alfa
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article