Benzoxaborole Antimalarial Agents. Part 4. Discovery of Potent 6-(2-(Alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles

[Image: see text] A series of 6-hetaryloxy benzoxaborole compounds was designed and synthesized for a structure–activity relationship (SAR) investigation to assess the changes in antimalarial activity which result from 6-aryloxy structural variation, substituent modification on the pyrazine ring, an...

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Autores principales: Zhang, Yong-Kang, Plattner, Jacob J., Easom, Eric E., Jacobs, Robert T., Guo, Denghui, Sanders, Virginia, Freund, Yvonne R., Campo, Brice, Rosenthal, Philip J., Bu, Wei, Gamo, Francisco-Javier, Sanz, Laura M., Ge, Min, Li, Liang, Ding, Jie, Yang, Yin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2015
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500456/
https://www.ncbi.nlm.nih.gov/pubmed/26067904
http://dx.doi.org/10.1021/acs.jmedchem.5b00678
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author Zhang, Yong-Kang
Plattner, Jacob J.
Easom, Eric E.
Jacobs, Robert T.
Guo, Denghui
Sanders, Virginia
Freund, Yvonne R.
Campo, Brice
Rosenthal, Philip J.
Bu, Wei
Gamo, Francisco-Javier
Sanz, Laura M.
Ge, Min
Li, Liang
Ding, Jie
Yang, Yin
author_facet Zhang, Yong-Kang
Plattner, Jacob J.
Easom, Eric E.
Jacobs, Robert T.
Guo, Denghui
Sanders, Virginia
Freund, Yvonne R.
Campo, Brice
Rosenthal, Philip J.
Bu, Wei
Gamo, Francisco-Javier
Sanz, Laura M.
Ge, Min
Li, Liang
Ding, Jie
Yang, Yin
author_sort Zhang, Yong-Kang
collection PubMed
description [Image: see text] A series of 6-hetaryloxy benzoxaborole compounds was designed and synthesized for a structure–activity relationship (SAR) investigation to assess the changes in antimalarial activity which result from 6-aryloxy structural variation, substituent modification on the pyrazine ring, and optimization of the side chain ester group. This SAR study discovered highly potent 6-(2-(alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles (9, 27–34) with IC(50)s = 0.2–22 nM against cultured Plasmodium falciparum W2 and 3D7 strains. Compound 9 also demonstrated excellent in vivo efficacy against P. berghei in infected mice (ED(90) = 7.0 mg/kg).
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spelling pubmed-45004562016-06-11 Benzoxaborole Antimalarial Agents. Part 4. Discovery of Potent 6-(2-(Alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles Zhang, Yong-Kang Plattner, Jacob J. Easom, Eric E. Jacobs, Robert T. Guo, Denghui Sanders, Virginia Freund, Yvonne R. Campo, Brice Rosenthal, Philip J. Bu, Wei Gamo, Francisco-Javier Sanz, Laura M. Ge, Min Li, Liang Ding, Jie Yang, Yin J Med Chem [Image: see text] A series of 6-hetaryloxy benzoxaborole compounds was designed and synthesized for a structure–activity relationship (SAR) investigation to assess the changes in antimalarial activity which result from 6-aryloxy structural variation, substituent modification on the pyrazine ring, and optimization of the side chain ester group. This SAR study discovered highly potent 6-(2-(alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles (9, 27–34) with IC(50)s = 0.2–22 nM against cultured Plasmodium falciparum W2 and 3D7 strains. Compound 9 also demonstrated excellent in vivo efficacy against P. berghei in infected mice (ED(90) = 7.0 mg/kg). American Chemical Society 2015-06-11 2015-07-09 /pmc/articles/PMC4500456/ /pubmed/26067904 http://dx.doi.org/10.1021/acs.jmedchem.5b00678 Text en Copyright © 2015 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Zhang, Yong-Kang
Plattner, Jacob J.
Easom, Eric E.
Jacobs, Robert T.
Guo, Denghui
Sanders, Virginia
Freund, Yvonne R.
Campo, Brice
Rosenthal, Philip J.
Bu, Wei
Gamo, Francisco-Javier
Sanz, Laura M.
Ge, Min
Li, Liang
Ding, Jie
Yang, Yin
Benzoxaborole Antimalarial Agents. Part 4. Discovery of Potent 6-(2-(Alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles
title Benzoxaborole Antimalarial Agents. Part 4. Discovery of Potent 6-(2-(Alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles
title_full Benzoxaborole Antimalarial Agents. Part 4. Discovery of Potent 6-(2-(Alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles
title_fullStr Benzoxaborole Antimalarial Agents. Part 4. Discovery of Potent 6-(2-(Alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles
title_full_unstemmed Benzoxaborole Antimalarial Agents. Part 4. Discovery of Potent 6-(2-(Alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles
title_short Benzoxaborole Antimalarial Agents. Part 4. Discovery of Potent 6-(2-(Alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles
title_sort benzoxaborole antimalarial agents. part 4. discovery of potent 6-(2-(alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500456/
https://www.ncbi.nlm.nih.gov/pubmed/26067904
http://dx.doi.org/10.1021/acs.jmedchem.5b00678
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