[Studies on the tissue schizonticide of malaria parasite: synthesis of derivatives of 2-substituted phenoxyprimaquine, 4-methylprimaquine and quinoxaline].
2-Substituted phenoxy-, 4-methyl-6-methoxy-8-aminoquinolines and 7-methoxy-5-aminoquinoxaline were condensed with 1-phthalimido-bromo-alkane to yield 2-substituted phenoxy-, 4-methyl-6-methoxy-8-(1-phthalimidoalkyl)-aminoquinolines (compounds 7-10 and 15-20) and 7-methoxy-5-(1-phthalimidoalkyl)aminoquinoxalines (28-30) which were subsequently reacted with hydrazine hydrate to give 2-substituted phenoxy-, 4-methyl-6-methoxy-8-(1-aminoalkyl)-aminoquinolines (11-14 and 22-27) and 7-methoxy-5-(1-aminoalkyl) aminoquinoxalines (31-33), respectively. The 2-substituted phenoxy-6-methoxy-8-aminoquinolines (4-6) were afforded by reduction of the corresponding 8-nitroquinolines (1-3) which were obtained by condensation of 2-chloro-6-methoxy-8-nitroquinoline and substituted phenols. Among them, compounds 25 and 24 were the most effective when evaluated in Plasmodium yoelii infected mice, no parasitemia was observed after a single oral dose of 10 mg/kg.
Chen
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Institute of Parasitic Diseases, Chinese Academy of Preventive Medicine, Shanghai.
Zheng
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Guo
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D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000627:therapeutic use; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010967:Plasmodium yoelii; D011319:Primaquine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity
D000962:Antimalarials; C077596:4-methyl-6-methoxy-8-(1-tetramethyleneamino)aminoquinoline; C077599:4-methyl-6-methoxy-8-(1-pentamethyleneamino)aminoquinoline; D011319:Primaquine