Benzoxaborole Antimalarial Agents. Part 4. Discovery of Potent 6-(2-(Alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-be n zoxaboroles
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...
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| Veröffentlicht in: | Journal of medicinal chemistry 2015-06, Vol.58 (13), p.5344-5354 |
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| container_end_page | 5354 |
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| container_issue | 13 |
| container_start_page | 5344 |
| container_title | Journal of medicinal chemistry |
| container_volume | 58 |
| creator | 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 |
| description | 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-be n zoxaboroles (9, 27-34) with IC50s = 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 (ED90 = 7.0 mg/kg). |
| doi_str_mv | 10.1021/acs.jmedchem.5b00678 |
| format | Article |
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| ispartof | Journal of medicinal chemistry, 2015-06, Vol.58 (13), p.5344-5354 |
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| language | eng |
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| source | American Chemical Society Journals |
| subjects | Plasmodium falciparum |
| title | Benzoxaborole Antimalarial Agents. Part 4. Discovery of Potent 6-(2-(Alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-be n zoxaboroles |
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