title: Novel diaryl ureas with efficacy in a mouse model of malaria.
abstract: Exploration of triclosan analogs has led to novel diaryl ureas with significant potency against in vitro cultures of drug-resistant and drug-sensitive strains of the human malaria parasite Plasmodium falciparum. Compound 18 demonstrated EC(50) values of 37 and 55 nM versus in vitro cultured parasite strains and promising in vivo efficacy in a Plasmodium berghei antimalarial mouse model, with >50% survival at day 31 post-treatment when administered subcutaneously at 256 mg/kg. This series of compounds provides a chemical scaffold of novel architecture, as validated by cheminformatics analysis, to pursue antimalarial drug discovery efforts.
authors: Department of Medicinal Chemistry, Jacobus Pharmaceutical Company, 37 Cleveland Lane, Princeton, NJ 08540, USA.
authors: John W
authors: JW
authors: Anderson
authors: Dimitri
authors: D
authors: Sarantakis
authors: Jacek
authors: J
authors: Terpinski
authors: T R Santha
authors: TR
authors: Kumar
authors: Han-Chun
authors: HC
authors: Tsai
authors: Mack
authors: M
authors: Kuo
authors: Arba L
authors: AL
authors: Ager
authors: William R
authors: WR
authors: Jacobs
authors: Guy A
authors: GA
authors: Schiehser
authors: Sean
authors: S
authors: Ekins
authors: James C
authors: JC
authors: Sacchettini
authors: David P
authors: DP
authors: Jacobus
authors: David A
authors: DA
authors: Fidock
authors: Joel S
authors: JS
authors: Freundlich
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D055808:Drug Discovery; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D001555:Benzene Derivatives; D014508:Urea