N-nonanoyl vanillylamide (1) is a synlhetic substitute of capsaicin (2), a pungent principle in red pepper. 1 was reacted with succinic anhydride. 3-chloro-1,2-propanediol, sodium chloroacetate, and 2-chloroethanol to furnish N-nonanoyl vanillylamide-4-succinyl ester (3), N-nonanoyl vanillylamide-4-glyceryl ether (4), sodium N-nonanoyl vanillylamide-4-O-acetate (5) and N-nonanoyl vanillylamide-4-glyceryl ether (6), respectively. A 3,4-methylenedioxy derivative of 1, N-nonanoyl piperonylamide (7), was synthesized form piperonylamine HCl and nonaoyl chloride. The ether analogues 4-6 all demonstrated marked antinociceptive and hypotensive effects without producing any overt irritation. In addition, these compounds revealed no untoward vagus reflex or transient hypertensive effect as previously found in 1 or 2.
嘉南學報 18期:p.A8-A13轉載Eur J Med Chem 27(3):p.187-192 (1992年)