title: Parallel synthesis and antimalarial screening of a 4-aminoquinoline library.
abstract: Due to growing problems with drug resistance, there is an outstanding need for new, cost-effective drugs for the treatment of malaria. The 4-aminoquinolines have provided a number of useful antimalarials, and Plasmodium falciparum, the causative organism for the most deadly form of human malaria, is generally slow to develop resistance to these drugs. Therefore, diverse screening libraries of quinolines continue to be useful for antimalarial drug discovery. We report herein the development of an efficient method for producing libraries of 4-aminoquinolines variant in the side chain portion of the molecule. The effects of these substitutions were evaluated by screening this library for activity against P. falciparum, revealing four potent compounds active against drug-resistant strains.
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143-2280, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Madrid
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Wilson
authors.forename: Joseph L
authors.initials: JL
authors.lastname: DeRisi
authors.forename: R Kiplin
authors.initials: RK
authors.lastname: Guy
mesh_terms: D000962:Antimalarials; D055808:Drug Discovery; D004351:Drug Resistance; D006801:Humans; D008288:Malaria; D016778:Malaria, Falciparum; D010963:Plasmodium falciparum
chemical_list: D000962:Antimalarials