Benzoxaborole antimalarial agents. Part 4. Discovery of potent 6-(2-(alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles.
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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苯唑替洛尔抗疟药。第4部分。发现有效的6-（2-（2-（AlkoxyCarbonyl）吡唑）-5-oxy）-1,3-二氢-1-羟基-2,1-苯并oxoxaboroles。
DOI：
10.1021/acs.jmedchem.5b00678
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发表时间：
2015-07-09
影响因子：
7.3
通讯作者：
Yang Y
中科院分区：
文献类型：
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作者：
Zhang YK;Plattner JJ;Easom EE;Jacobs RT;Guo D;Sanders V;Freund YR;Campo B;Rosenthal PJ;Bu W;Gamo FJ;Sanz LM;Ge M;Li L;Ding J;Yang Y
设计合成了一系列6-六芳氧基苯并氧硼环化合物，用于构效关系(SAR)研究，以评价6-芳氧基结构变化、吡嗪环上取代基修饰以及侧链酯基优化对抗疟活性的影响。这项研究发现6-(2-(alkoxycarbonyl)pyrazinyl-5-oxy)-1，3-dihydro-1-hydroxy-2，1-benzoxaboroles(9，27-34)对培养的恶性疟W2和3D7株有很强的抑制作用，其IC50=0.2-22 nm。化合物9在小鼠体内对伯氏假单胞菌也表现出良好的杀灭效果(ED90=7.0 mg/kg)。
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).