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...

Descripción completa

Detalles Bibliográficos
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
Descripción
Sumario:[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).

Ejemplares similares