STUDIES ON TISSUE SCHIZONTICIDE OF MALARIA PARASITE:SYNTHESIS OF 2-SUBSTITUTED BENZYLOXY(OR METHOXY)-5- SUBSTITUTED PHENOXY ANALOGUES OF PRIMAQUINE

2- Chloro- 6-methoxy- 8- nitroquinoline was reacted with substituted benzyl alcohols(or sodium methanol)and then brominated to give 2-substituted benzyloxy-6-methoxy-and 2, 6-dimethoxy-5-bromo-8-nitroquinolines (compounds 5～8 in Table 1). These products were condensed with substituted phenols to form corresponding 5-substituted phenoxy compounds (9～19 in Tables 1 and 2 )which were subsequently reduced to afford 2- substituted benzyloxy- 6- methoxy- and 2,6-dimethoxy- 5- substituted phenoxy- 8-aminoquinolines (20～28, 47 and 48 in Tables 3 and 6). Condensation with 4-bromophthalimidopentane yielded corresponding 8-(4-phthalimido-1-methylbutyl)aminoquinolines (29～37, 49 and 50 in Tables 4 and 6)which were subsequently treated with hydrazine hydrate to give 2- substituted benzyloxy-6-methoxy- and 2, 6-dimethoxy- 5- substituted phenoxy- 8- ( 4- amino- 1 -methylbutyl)amino-quinolines, compounds Ⅲ and Ⅳ(38～46, 51 and 52 in Tables 5 and 6), the analogues of primaquine. Compounds Ⅲ and Ⅳ were tested against Plasmodium yoerii/ in mice infected with sporozoites. The parasitaemia of 80% and 90% of tested mice was negative at an oral single dose of 100mg/kg of compounds 39 and 45, respectively. The results of further studies on compound 45 showed that the parasitaemia of 80% of mice was negative at a single dose of 20 mg/kg, and the acute toxicity in mice was less than that of primaquine.