Lead selection of a new aminomethylphenol, JPC-3210, for malaria treatment and prevention

Marina Chavchich; Geoffrey W. Birrell; Arba L. Ager; Donna O. MacKenzie; Gavin D. Heffernan; Guy A. Schiehser; Laura R. Jacobus; G. Dennis Shanks; David P. Jacobus; Michael D. Edstein

doi:10.1128/AAC.03066-15

Lead selection of a new aminomethylphenol, JPC-3210, for malaria treatment and prevention

Marina Chavchich, Geoffrey W. Birrell, Arba L. Ager, Donna O. MacKenzie, Gavin D. Heffernan, Guy A. Schiehser, Laura R. Jacobus, G. Dennis Shanks, David P. Jacobus, Michael D. Edstein

Microbiology & Immunology

Research output: Contribution to journal › Article

12 Scopus citations

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.

Original language	English (US)
Pages (from-to)	3115-3118
Number of pages	4
Journal	Antimicrobial agents and chemotherapy
Volume	60
Issue number	5
DOIs	https://doi.org/10.1128/AAC.03066-15
State	Published - May 2016

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

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Chavchich, M., Birrell, G. W., Ager, A. L., MacKenzie, D. O., Heffernan, G. D., Schiehser, G. A., Jacobus, L. R., Shanks, G. D., Jacobus, D. P., & Edstein, M. D. (2016). Lead selection of a new aminomethylphenol, JPC-3210, for malaria treatment and prevention. Antimicrobial agents and chemotherapy, 60(5), 3115-3118. https://doi.org/10.1128/AAC.03066-15

Lead selection of a new aminomethylphenol, JPC-3210, for malaria treatment and prevention. / Chavchich, Marina; Birrell, Geoffrey W.; Ager, Arba L.; MacKenzie, Donna O.; Heffernan, Gavin D.; Schiehser, Guy A.; Jacobus, Laura R.; Shanks, G. Dennis; Jacobus, David P.; Edstein, Michael D.

In: Antimicrobial agents and chemotherapy, Vol. 60, No. 5, 05.2016, p. 3115-3118.

Research output: Contribution to journal › Article

Chavchich, Marina ; Birrell, Geoffrey W. ; Ager, Arba L. ; MacKenzie, Donna O. ; Heffernan, Gavin D. ; Schiehser, Guy A. ; Jacobus, Laura R. ; Shanks, G. Dennis ; Jacobus, David P. ; Edstein, Michael D. / Lead selection of a new aminomethylphenol, JPC-3210, for malaria treatment and prevention. In: Antimicrobial agents and chemotherapy. 2016 ; Vol. 60, No. 5. pp. 3115-3118.

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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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