2. Academic Validation
  3. Lead Selection of a New Aminomethylphenol, JPC-3210, for Malaria Treatment and Prevention

Lead Selection of a New Aminomethylphenol, JPC-3210, for Malaria Treatment and Prevention

  • Antimicrob Agents Chemother. 2016 Apr 22;60(5):3115-8. doi: 10.1128/AAC.03066-15.
Marina Chavchich 1,  Geoffrey W Birrell 1,  Arba L Ager 2,  Donna O MacKenzie 1,  Gavin D Heffernan 3,  Guy A Schiehser 3,  Laura R Jacobus 3,  G Dennis Shanks 1,  David P Jacobus 3,  Michael D Edstein 4
Affiliations

Affiliations

  • 1 Department of Drug Evaluation, Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia.
  • 2 University of Miami, Miami, Florida, USA.
  • 3 Jacobus Pharmaceutical Company, Princeton, New Jersey, USA.
  • 4 Department of Drug Evaluation, Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia mike.edstein@defense.gov.au.
PMID: 26856849 DOI: 10.1128/AAC.03066-15
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.

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