STUDIES ON THE SYNTHESIS OF SALICYLAMIDES AND ALKAMINE SALTS OF NICLOSAMIDE AND THEIR ACTIVITIES AGAINST SCHISTOSOMA JAPONICUM AND ONCOMELANIA

Two series of salicylamides (Ⅰ and Ⅱ) and alkamine salts of niclosamide (Ⅲ) have been prepared. Methyl salicylate was reacted with hydroperoxide and hydrochloric acid, and then condensed with amines to afford 5-chlorosalicylamides (Ⅰ). Reaction of salicylamide or 5-chloro-salicylamide with formaldehyde and cyclic aliphatic amine through Mannich reaction provided compounds (Ⅱ). Aliphatic amine salts of niclosamide (Ⅲ) were obtained by adding amines to niclosamide.Compounds of the Ⅲ series were found to possess pronounced activity against Oncomelania and cercaria of Schistosoma japonicum in mice. Among them compound Ⅲa exhibited a rather good cidal effect against 20-day-old immature Schistosomes by oral administration. But compounds of the Ⅰ and Ⅱ series showed no activity.