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A novel 4-aminoquinoline derivative [(S )-7-chloro-N -(4-methyl-1-(4-methylpiperazin-1-yl)pentan-2-yl)-quinolin-4-amine triphosphate] exhibiting curative activity against chloroquine-resistant malaria parasites has been identified for preclinical development as a blood schizonticidal agent. The lead molecule selected after detailed structure-activity relationship (SAR) studies has good solid-state properties and promising activity againstin vitro andin vivo experimental malaria models. Thein vitro absorption, distribution, metabolism, and excretion (ADME) parameters indicate a favorable drug-like profile.

Synthesis and Evaluation of Chirally Defined Side Chain Variants of 7-Chloro-4-Aminoquinoline To Overcome Drug Resistance in Malaria Chemotherapy