title: [Synthesis and PPAR activities of novel phenylacetic acid derivatives containing sulfonamide moiety].
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.
authors: School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
authors: Yan
authors: Y
authors: Yang
authors: Ju-Fang
authors: JF
authors: Yan
authors: Li
authors: L
authors: Fan
authors: Xin
authors: X
authors: Chen
authors: Li
authors: L
authors: Jiang
authors: Da-Cheng
authors: DC
authors: Yang
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D005227:Fatty Acids / Q000737:chemistry; D056945:Hep G2 Cells / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D010648:Phenylacetates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry
chemical_list: D000814:Aniline Compounds; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D047492:Peroxisome Proliferator-Activated Receptors; D010648:Phenylacetates; D013449:Sulfonamides; C109911:4-aminophenylacetic acid; C025136:phenylacetic acid