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
  • 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 [email protected].
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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