STUDIES ON ANTIMALARIALS Ⅲ. SYNTHESIS AND ANTIMALARIAL ACTIVITIES OF SOME DERIVATIVES OF 2,4-DIAMINO-6-SUBSTITUTED PIPERAZINYL QUINAZOLINES

A series of 2,4-diamino-6-substituted piperazine quinazolines was synthesized. The key intermediates of the substituted piperazino-2-aminobenzonitriles were synthesized from m-chloro-benzonitrile by nitration, reacting with piperazine, reduction and condensation with various substituted halogen compounds. They were cyclized smoothly with cyanoguanidine to form 2,4-diamino-6-substituted piperazinoquinazolines. The latter could also be prepared by the condensation of 2-nitro-5-chloro-benzonitrile with the substituted piperazines, followed by reduction and cyclization with cyanoguanidine.After primary screening tests on infected mice, it was found that among these compounds four of them (compounds X_1,2,3,8) showed suppressive effect on Plasmodium berghei, and three compounds (X_1,8,10) possessed causal prophylactive activity against P. yoelii. They were also screened for sporontocidal activity using P. gallinaccum-Ae, albopictus system, with the result that the sporogony of the parasite was inhibited in 70% of the infected mosquitoes by two of these compounds (X_8,9) at a concentration of 0.01%.