4-AMINOQUINOLINES - PAST, PRESENT, AND FUTURE - A CHEMICAL PERSPECTIVE

The 4-aminoquinoline chloroquine (I) can be considered to be one of th e most important synthetic chemotherapeutic agents in history, Since i ts discovery, chloroquine has proved to be a highly effective, safe, a nd well tolerated drug for the treatment and prophylaxis of malaria, H owever, the emergence of chloroquine-resistant strains of the malarial parasite has underlined the requirement for a synthetic alternative t o 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 toxicit y also is included, with a brief description of potential approaches t o the design of new synthetic derivatives. (C) 1998 Elsevier Science I nc.