Synthesis and PPAR activities of novel phenylacetic acid derivatives containing sulfonamide moiety.
- Author:
Yan YANG
1
;
Ju-Fang YAN
;
Li FAN
;
Xin CHEN
;
Li JIANG
;
Da-Cheng YANG
Author Information
1. School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
- Publication Type:Journal Article
- MeSH:
Aniline Compounds;
chemistry;
Fatty Acids;
chemistry;
Hep G2 Cells;
metabolism;
Humans;
Hypoglycemic Agents;
chemical synthesis;
chemistry;
pharmacology;
Molecular Structure;
Peroxisome Proliferator-Activated Receptors;
metabolism;
Phenylacetates;
chemical synthesis;
chemistry;
pharmacology;
Structure-Activity Relationship;
Sulfonamides;
chemistry
- From:
Acta Pharmaceutica Sinica
2012;47(12):1630-1639
- CountryChina
- Language:Chinese
-
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.
