Synthesis and hypoglycemic activity of S-acyl derivatives of 3-mercaptopicolinic acid.
A series of S-alkanoyl and benzoyl derivatives of 3-mercaptopicolinic acid (3-MPA) was prepared and studied for hypoglycemic activity. Three alkanoyl derivatives (propionyl, pivaloyl, and 1-adamantanecarbonyl, 19-21) were prepared with increasing bulk around the thio ester bond. The benzoyl derivatives contained aromatic substituents chosen from a sigma-pi cluster chart so that the esters prepared had a wide range of electronic and solubility properties. In general, compounds with substituents which increased lipid solubility [p-chlorobenzoyl (4), p-trifluoromethylbenzoyl (6), and pivaloyl (20)] had the greatest potency at a dose of 300 mg/kg. Hydrolysis rates, measured at pH 6 and 8, indicated that in vivo breakdown to 3-MPA probably did not account for the observed hypoglycemic activity of the esters. 4, 6, and 20 were less potent than 3-MPA in comparative dose range studies.
D000215:Acylation; D000818:Animals; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007004:Hypoglycemic Agents / Q000138:chemical synthesis*; D008297:Male; D008722:Methods; D010848:Picolinic Acids / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
D007004:Hypoglycemic Agents; D010848:Picolinic Acids