Synthesis and hypoglycemic activity of benzamidophenyl-alkanoic acid derivates: new inhibitors of gluconeogenesis.
A series of omega-[2-(N-alkylbenzamido)-phenyl]-alkanoic acids was synthesized and tested for its effects on blood glucose concentration in fasted rats and on gluconeogenesis from lactate and pyruvate in isolated perfused rat livers. The compounds led to a dose-dependent and reversible inhibition of gluconeogenesis, with 4-[2-(N-methyl-3-trifluoromethylbenzamido)-phenyl]-butanoic acid leading to a 50% inhibition at 0.02 mM. The compounds lowered blood glucose in fasted rats. No correlation between hypoglycemic effect and inhibition of gluconeogenesis could be detected, however.
D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D005943:Gluconeogenesis / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis*; D007700:Kinetics; D007928:Lethal Dose 50; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D001549:Benzamides; D001786:Blood Glucose; D007004:Hypoglycemic Agents