Application of multicomponent reactions to antimalarial drug discovery. Part 3: Discovery of aminoxazole 4-aminoquinolines with potent antiplasmodial activity in vitro

• Published in: Bioorganic & medicinal chemistry letters Vol. 17; no. 17; pp. 4733 - 4736
• Main Authors: Musonda, Chitalu C., Little, Susan, Yardley, Vanessa, Chibale, Kelly
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.09.2007; Elsevier
• Subjects: 4-Aminoquinolines; Aminoquinolines - chemistry; Aminoxazoles; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - chemical synthesis; Antimalarials - pharmacology; Antiparasitic agents; Antiplasmodial activity; Biological and medical sciences; Chemistry, Pharmaceutical - methods; Drug Design; Drug Evaluation, Preclinical; Inhibitory Concentration 50; Malaria; Medical sciences; Oxazoles - chemistry; P. falciparum; Parasitic Sensitivity Tests; Pharmacology. Drug treatments; Plasmodium - metabolism; Plasmodium falciparum; Plasmodium falciparum - drug effects; Structure-Activity Relationship; Antiplasmodial activity; 4-Aminoquinolines; Malaria; P. falciparum; Aminoxazoles; Protozoa; Antimalarial; Apicomplexa; Nitrogen heterocycle; Quinoline derivatives; Morpholine derivatives; In vitro; Antiprotozoal agent; Plasmodium falciparum; Structure activity relation; Chlorine Organic compounds; Parasiticide; Piperazine derivatives; Chemical synthesis; Oxazole derivatives; Oxygen nitrogen heterocycle
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2007.06.070

The synthesis and biological activity of a new series of 4-aminoquinoline-containing 2,4,5-trisubstituted aminoxazoles is described. The synthesis and antimalarial activity of a novel series of first generation 4-aminoquinoline-containing 2,4,5-trisubstituted aminoxazoles against two strains of the Plasmodium falciparum parasite in vitro is described. A number of compounds significantly more potent than the standard drug chloroquine were identified.