title: Antimalarial aminothiazoles and aminopyridines from phenotypic whole-cell screening of a SoftFocus(®) library.
abstract: The current state of antimalarial drug resistance emphasizes the need for new therapies with novel modes of action that will add a significant benefit compared with current standards. In this regard, high throughput phenotypic whole-cell screening aids the discovery of novel antiplasmodial scaffolds that are inherently suited to hit-to-lead and lead-optimization efforts. The aminothiazoles and aminopyridines exemplify two such compound classes stemming from whole-cell screening. Respective structure-activity relationship determinations and subsequent optimization around these scaffolds led to frontrunner compounds in each series, which possess the desired antimalarial efficacy, bioavailability and metabolic stability to further progress medicinal chemistry programs.
authors.affiliation: Department of Chemistry, University of Cape Town, Private Bag X3, Rondebosch 7701, South Africa.
authors.forename: Tanya
authors.initials: T
authors.lastname: Paquet
authors.forename: Richard
authors.initials: R
authors.lastname: Gordon
authors.forename: David
authors.initials: D
authors.lastname: Waterson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Witty
authors.forename: Kelly
authors.initials: K
authors.lastname: Chibale
mesh_terms: D000631:Aminopyridines / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D062313:Databases, Pharmaceutical; D004351:Drug Resistance; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D021261:Parasitic Sensitivity Tests / Q000379:methods; D010963:Plasmodium falciparum / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000631:Aminopyridines; D000962:Antimalarials; D013844:Thiazoles