- Benzoxaborole Antimalarial Agents. Part 4. Discovery of Potent 6-(2-(Alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles
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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 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).
- 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
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p. 5344 - 5354
(2015/08/03)
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- Pyrazinoic Acid Esters with Broad Spectrum in Vitro Antimycobacterial Activity
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A series of substituted pyrazinoic acid esters has been prepared and examined for their in vitro activity against Mycobacterium avium and Mycobacterium kansasii as well as mycobacterium tuberculosis.Modification of both the pyrazine nucleus and the ester functionality have been very successfull in expanding the activity of pyrazinamide to include M. avium and M. kansasii, organisms normally not susceptible to pyrazinamide.Several of these compounds have activities 100-1000-fold greater than that of pyrazinamide against M. tuberculosis.
- Cynamon, Michael H.,Gimi, Rayomand,Gyenes, Ferenc,Sharpe, Cindy A.,Bergmann, Kathryn E.,et al.
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p. 3902 - 3907
(2007/10/02)
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