[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.