title: Lead Selection of a New Aminomethylphenol, JPC-3210, for Malaria Treatment and Prevention.
abstract: Structure-activity relationship studies of trifluoromethyl-substituted pyridine and pyrimidine analogues of 2-aminomethylphenols (JPC-2997, JPC-3186, and JPC-3210) were conducted for preclinical development for malaria treatment and/or prevention. Of these compounds, JPC-3210 [4-(tert-butyl)-2-((tert-butylamino)methyl)-6-(5-fluoro-6-(trifluoromethyl)pyridin-3-yl)phenol] was selected as the lead compound due to superior in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum lines, lower in vitro cytotoxicity in mammalian cell lines, longer plasma elimination half-life, and greater in vivo efficacy against murine malaria.
authors: Department of Drug Evaluation, Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia.
authors: Marina
authors: M
authors: Chavchich
authors: Department of Drug Evaluation, Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia.
authors: Geoffrey W
authors: GW
authors: Birrell
authors: University of Miami, Miami, Florida, USA.
authors: Arba L
authors: AL
authors: Ager
authors: Department of Drug Evaluation, Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia.
authors: Donna O
authors: DO
authors: MacKenzie
authors: Jacobus Pharmaceutical Company, Princeton, New Jersey, USA.
authors: Gavin D
authors: GD
authors: Heffernan
authors: Jacobus Pharmaceutical Company, Princeton, New Jersey, USA.
authors: Guy A
authors: GA
authors: Schiehser
authors: Jacobus Pharmaceutical Company, Princeton, New Jersey, USA.
authors: Laura R
authors: LR
authors: Jacobus
authors: Department of Drug Evaluation, Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia.
authors: G Dennis
authors: GD
authors: Shanks
authors: Jacobus Pharmaceutical Company, Princeton, New Jersey, USA.
authors: David P
authors: DP
authors: Jacobus
authors: Department of Drug Evaluation, Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia mike.edstein@defense.gov.au.
authors: Michael D
authors: MD
authors: Edstein
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002460:Cell Line; D006224:Cricetinae; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D016778:Malaria, Falciparum / Q000188:drug therapy*; D015767:Mefloquine / Q000627:therapeutic use; D051379:Mice; D010636:Phenols / Q000627:therapeutic use*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000472:pathogenicity; D011725:Pyridines / Q000627:therapeutic use
chemical_list: D000962:Antimalarials; C000600814:JPC-2997; D010636:Phenols; D011725:Pyridines; D015767:Mefloquine