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• W2086108526 abstract "Abstract Three rationally designed isomeric aryl-bridged bis-quinolines, N1,Nx-bis(7-chloroquinolin-4-yl)phenylene-1,x-diamines, where x = 2, 3 or 4, i.e. o-, m- and p-substituted analogues respectively, were synthesized and evaluated against Plasmodium berghei in-vivo. The compound with x = 2 had an ID50 of 30 mg kg−1, whereas the p-substituted analogue (x = 4) was not statistically schizonticidal at either of the two dose levels tested in olive oil-dimethylsulphoxide (5 and 25 mg kg−1, ID50 = 60 mg kg−1 approx.). When the delivery vehicle was changed to saline-DMSO, antimalarial potency increased for the p-substituted compound (ID50 17mg kg−1). In contrast, the m-substituted analogue had marked antimalarial activity (ID50 1.2 mg kg−1), which compares favourably with that of chloroquine diphosphate (ID50 = 4.3 mg kg−1). The data presented show that the amino-methylene side chain in amodiaquine can be successfully replaced by a 7-halo-4-aminoquinoline, establishing that carbon bridges containing less than four contiguous carbon atoms can be present within highly active aryl-substituted 4-aminoquinoline antimalarials. These results confirm that the presence of an OH group in the aryl bridge is not necessary for antimalarial activity and substantiate the view that, despite the appearance of resistant strains, new and existing aminoquinolines still have an important role in treating malaria." @default.
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• W2086108526 date "1998-05-01" @default.
• W2086108526 modified "2023-10-03" @default.
• W2086108526 title "Novel Aryl-bis-quinolines with Antimalarial Activity In-vivo" @default.
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• W2086108526 doi "https://doi.org/10.1111/j.2042-7158.1998.tb06189.x" @default.
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