Studies on Hypolipidemic Agents. I. Synthesis and Pharmacological Properties of Nicotinic Acid-Ethanolamine Derivatives

概要

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A series of nicotinic acid-ethanolamine derivatives was synthesized and evaluated pharmacologically and biochemically in mice and rats. Many compounds showed considerable hypolipidemic activity in two models : hypercholesterolemic mice and hypertriglyceridemic rats. The results clarified some structure-activity relationships ; there was an increase in efficacy resulting from the introduction of alkyl or aryl groups on the nitrogen of the ethanolamine part. Furthermore, it was clearly shown that coupling of ethanolamines with nicotinic acid (NA) resulted in a marked decrease in toxicity. Among the compounds tested, 2-(N-isopropyl-N-nicotinoylamino) ethyl nicotinate (20) was found to possess more favorable pharmacological and toxicological profiles than NA. Studies on 20 indicated that its hypolipidemic effect might be attributable to NA released by hydrolysis in vivo of the ester linkage. After administration of 20,the maximum serum level of free NA was approximately 4 times lower and the persistence of NA level in the serum was longer than that of the NA-treated group.
社団法人日本薬学会の論文
1983-11-25