Synthesis and PPAR activities of novel phenylacetic acid derivatives containing sulfonamide moiety / 药学学报
Acta Pharmaceutica Sinica
;
(12): 1630-1639, 2012.
Article
in Chinese
| 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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Phenylacetates
/
Structure-Activity Relationship
/
Sulfonamides
/
Molecular Structure
/
Chemistry
/
Peroxisome Proliferator-Activated Receptors
/
Fatty Acids
/
Hep G2 Cells
/
Hypoglycemic Agents
Limits:
Humans
Language:
Chinese
Journal:
Acta Pharmaceutica Sinica
Year:
2012
Type:
Article
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