Application of multi-component reactions to antimalarial drug discovery. Part 1: Parallel synthesis and antiplasmodial activity of new 4-aminoquinoline Ugi adducts

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 15; pp. 3901 - 3905
• Main Authors: Musonda, Chitalu C, Taylor, Dale, Lehman, Julie, Gut, Jiri, Rosenthal, Philip J, Chibale, Kelly
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 02.08.2004; Elsevier
• Subjects: 4-Aminoquinolines; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Antiparasitic agents; Biological and medical sciences; Chloroquine - chemistry; Malaria; Medical sciences; Mefloquine - chemistry; Miscellaneous; Molecular Conformation; Molecular Structure; Pharmacology. Drug treatments; Plasmodium falciparum - drug effects; Quinine - chemistry; Structure-Activity Relationship; Ugi isocyanide multi-component reactions; Malaria; 4-Aminoquinolines; Ugi isocyanide multi-component reactions; Protozoa; Antimalarial; Apicomplexa; Ugi reaction; Chloroquine; Combinatorial chemistry; Quinoline derivatives; Biological activity; Resistance; Antiprotozoal agent; Plasmodium falciparum; Parasiticide; Chemical synthesis; Molecular adduct
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.05.063

Graphic The synthesis of a new class of Ugi adducts incorporating the 4-aminoquinoline moiety is described. The novel compounds are active against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum with the best compound showing an IC 50 value of 73 nM against a resistant K1 strain.