4-Aminoquinolines--past, present, and future: a chemical perspective.
The 4-aminoquinoline chloroquine (1) can be considered to be one of the most important synthetic chemotherapeutic agents in history. Since its discovery, chloroquine has proved to be a highly effective, safe, and well-tolerated drug for the treatment and prophylaxis of malaria. However, the emergence of chloroquine-resistant strains of the malarial parasite has underlined the requirement for a synthetic alternative to chloroquine. This review describes structure-activity relationships for the 4-aminoquinolines, along with views on the mechanism of action and parasite resistance. A description of drug metabolism and toxicity also is included, with a brief description of potential approaches to the design of new synthetic derivatives.
O'Neill
P M
PM
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Bray
P G
PG
Hawley
S R
SR
Ward
S A
SA
Park
B K
BK
D000634:Aminoquinolines / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000378:metabolism / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D015195:Drug Design; D006418:Heme / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D013329:Structure-Activity Relationship
D000634:Aminoquinolines; D000962:Antimalarials; D006418:Heme; D002738:Chloroquine; D004247:DNA; C001920:4-aminoquinoline