title: 4-Aminoquinolines--past, present, and future: a chemical perspective.
abstract: 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.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Liverpool, UK.
authors.forename: P M
authors.initials: PM
authors.lastname: O'Neill
authors.forename: P G
authors.initials: PG
authors.lastname: Bray
authors.forename: S R
authors.initials: SR
authors.lastname: Hawley
authors.forename: S A
authors.initials: SA
authors.lastname: Ward
authors.forename: B K
authors.initials: BK
authors.lastname: Park
mesh_terms: 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
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D006418:Heme; D002738:Chloroquine; D004247:DNA; C001920:4-aminoquinoline