4-aminoquinolines - Past, present, and future: A chemical perspective

The 4-aminoquinoline chloroquine (I) 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. (C) 1998 Elsevier Science Inc.