Synthesis and PPAR activities of novel phenylacetic acid derivatives containing sulfonamide moiety / 药学学报
Acta Pharmaceutica Sinica
;
(12): 1630-1639, 2012.
Article
Dans Chinois
| WPRIM
| ID: wpr-274611
ABSTRACT
The discovery of high performance leading antidiabetic compounds containing sulfonamide and 4-aminophenylacetic acid moieties is reported. This was achieved by the synthesis of 6 intermediates and subsequently 20 target molecules using 4-aminophenylacetic acid as the starting materials, and through a few synthetic routes aided by multi-step reactions including sulfonylation of amino group, deacylation of amides and esterification of carboxyl group, as well as acylation of amino group. The chemical structures of the twenty-four new compounds were determined using 1H NMR, 13C NMR and HR-MS techniques. Screening in vitro of their peroxisome proliferator-activated receptor (PPAR) activation activities showed weak relative PPAR activation activities to most of the target molecules. However, 4 target molecules exhibit PPAR over 58%, and as high as 81.79% for TM2-i, presenting itself as potent leading compound for antidiabetic drugs. This research also confirms that it is probable to achieve esterification of carboxyl group and deacylation of fatty acid N-phenyl amides concurrently in SOCl2/alcohol solvent system. This provides new synthetic method for the selective reaction within molecules containing both carboxyl and N-aryl amido groups of fatty acids.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Pharmacologie
/
Phénylacétates
/
Relation structure-activité
/
Sulfonamides
/
Structure moléculaire
/
Chimie
/
Récepteurs activés par les proliférateurs de peroxysomes
/
Acides gras
/
Cellules HepG2
/
Hypoglycémiants
Limites du sujet:
Humains
langue:
Chinois
Texte intégral:
Acta Pharmaceutica Sinica
Année:
2012
Type:
Article
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