STUDIES ON NEW ANTIMALARIALS SYNTHESIS OF DERIVATIVES OF SUBSTITUTED 5-PHENOXY-6-METHOXY-8-AMINOQUINOLINE

5-(p-Fluorophenoxy)-6-methoxy-8-(4-amino-1-methylbutylamino)-quinolinc (Ⅰ₁) has been reported to be more potent and less toxic than primaquine for radical cure against Plasmodium cynomolgi in monkeys. This compound coded M7844 as well as a series of derivatives 5-phenoxy-6-methoxy-8-(4-substituent-amino-1-methyl-butylamino) quinolincs (Ⅰ_2～17) and their isomers 5-phcnoxy-6-mcthoxy-8-(5-substituent-amino-amylamino) quinolines (Ⅱ_18～28) were synthesized.Compounds Ⅰ and Ⅱ were synthesized from 6-methoxy-8-nitroquinoline by bromination, condensation and reduction to give 5-phenoxy-6-methoxy-8-aminoquinolines which were subsequently reacted with 4-bromo-1-phthalimidopentane or 5-bromo-1-phthalimidopentane to yield the corresponding compounds 5-phenoxy-6-methoxy-8-(4-phthalimido-1-methylbutylamino)quinolincs Ⅰ_10～17 (Table 1) or their isomers 5-phenoxy-6-mcthoxy-8-(5-phthalimidoamylamino) quinolines Ⅱ_24～28 (Table 2). They were subsequently hydrolyzcd, and then prepared as their salts Ⅰ_1～9 (Table 1) or their isomers Ⅱ_18～23 (Table 2).Compounds Ⅰ_1～7, Ⅰ₁₆ and Ⅱ₁₈ exhibited some activities against P. yoelii in mice. Preliminary experiments showed that M7844 (Ⅰ₁) possessed activity against P. cynomolgi in monkeys, but less effective than primaquine at the same dosage. M7844 is 20 times less toxic and 4～5 times less effective than primaquine in mice.