Studies on Amide Derivatives of Higher Fatty Acids. I. The Relationship between Chemical Structure and Cholesterol Lowering Activity

Abstract

Many novel amide derivatives of higher fatty acids were synthesized to study the relationship between chemical structure and the serum cholesterol-lowering activity in mice. In a series of cyclohexylamides of higher fatty acids, the cholesterol-lowering activity was enhanced with increasing number of carbon atoms and number of unsaturated double bonds. Introduction of substituents into the cyclohexyl ring of N-cyclohexyllinoleamide did not increase the cholesterollowering activity, while significant improvement of the activity was observed by introduction of a methyl group or a chlorine atom into the phenyl ring of N-phenyllinoleamide. In all the substituted groups tested except the acetyl group, derivatives substituted at 2-position in the N-cyclohexyl-and N-phenyl-linoleamides showed a higher activity than these substituted in other positions. As a result, N-(2-methyl-6-chlorophenyl) linoleamide was found to be the most potent agent in the present study.