Synthesis of Deuterated Endochin-Like Quinolones
Corresponding Author
Sovitj Pou
Medical Research Service, VA Healthcare System, Portland, Oregon, USA
Correspondence:
Sovitj Pou ([email protected])
Search for more papers by this authorRolf W. Winter
Medical Research Service, VA Healthcare System, Portland, Oregon, USA
Search for more papers by this authorKatherine M. Liebman
Medical Research Service, VA Healthcare System, Portland, Oregon, USA
Search for more papers by this authorRosie A. Dodean
Medical Research Service, VA Healthcare System, Portland, Oregon, USA
Search for more papers by this authorAaron Nilsen
Medical Research Service, VA Healthcare System, Portland, Oregon, USA
Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, Oregon, USA
Search for more papers by this authorAndrea DeBarber
Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, Oregon, USA
Search for more papers by this authorJ. Stone Doggett
Medical Research Service, VA Healthcare System, Portland, Oregon, USA
Division of Infectious Diseases, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA
Search for more papers by this authorMichael K. Riscoe
Medical Research Service, VA Healthcare System, Portland, Oregon, USA
Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, USA
Search for more papers by this authorCorresponding Author
Sovitj Pou
Medical Research Service, VA Healthcare System, Portland, Oregon, USA
Correspondence:
Sovitj Pou ([email protected])
Search for more papers by this authorRolf W. Winter
Medical Research Service, VA Healthcare System, Portland, Oregon, USA
Search for more papers by this authorKatherine M. Liebman
Medical Research Service, VA Healthcare System, Portland, Oregon, USA
Search for more papers by this authorRosie A. Dodean
Medical Research Service, VA Healthcare System, Portland, Oregon, USA
Search for more papers by this authorAaron Nilsen
Medical Research Service, VA Healthcare System, Portland, Oregon, USA
Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, Oregon, USA
Search for more papers by this authorAndrea DeBarber
Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, Oregon, USA
Search for more papers by this authorJ. Stone Doggett
Medical Research Service, VA Healthcare System, Portland, Oregon, USA
Division of Infectious Diseases, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA
Search for more papers by this authorMichael K. Riscoe
Medical Research Service, VA Healthcare System, Portland, Oregon, USA
Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, USA
Search for more papers by this authorFunding: This project was supported with funds from the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Program Award number i01 BX003312 (M.K.R.). M.K.R. is a recipient of a VA Research Career Scientist Award (14S-RCS001). Research reported in this publication was also supported by the US National Institutes of Health under award numbers R01AI100569 and R01AI141412 (M.K.R.) and by the US Department of Defense Peer Reviewed Medical Research Program (PR181134) (M.K.R.). This work was also funded by VA Merit Review Award BX004522 to JSD from the US Department of Veterans Affairs Biomedical Laboratory Research and Development. The National Science Foundation provided instrument funding for the BioAnalytical Mass Spectrometry Facility at Portland State University (NSF, MRI 1828573), which was used to generate HRMS analytical measurements.
ABSTRACT
Malaria continues to be a serious and debilitating disease. The emergence and spread of high-level resistance to multiple antimalarial drugs by Plasmodium falciparum has brought about an urgent need for new treatments that will be active against multidrug resistant malaria infections. One such treatment, ELQ-331 (MMV-167), an alkoxy carbonate prodrug of 4(1H)-quinolone ELQ-300, is currently in preclinical development with the Medicines for Malaria Venture. Clinical development of ELQ-331 or similar compounds will require the availability of isotopically labeled analogs. Unfortunately, a suitable method for the deuteration of these important compounds was not found in the literature. Here, we describe a facile and scalable method for the deuteration of 4(1H)-quinolone ELQ-300, its alkoxycarbonate prodrug ELQ-331, and their respective N-oxides using deuterated acetic acid.
Conflict of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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