Potent antimalarial 4-pyridones with improved physico-chemical properties
Potent antimalarial 4-pyridones with improved physico-chemical properties
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DOI：
10.1016/j.bmcl.2011.07.044
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发表时间：
2011-09-15
影响因子：
2.7
通讯作者：
Gargallo-Viola, Domingo
中科院分区：
文献类型：
--
作者：
Bueno, Jose M.;Manzano, Pilar;Gargallo-Viola, Domingo
抗疟药4-吡啶酮是一类新型的疟原虫线粒体电子传递链抑制剂，靶向细胞色素bc 1（复合物III）。一般而言，最有效的4-吡啶酮是亲脂性分子，在水性介质中的溶解度差，在固体剂型的临床前物种中的口服生物利用度低。引入极性羟甲基的策略使我们能够保持对其他亲脂性更强的类似物观察到的高水平抗疟效力，同时改善临床前物种中的溶解度和口服生物利用度。(C)2011爱思唯尔有限公司保留所有权利。
Antimalarial 4-pyridones are a novel class of inhibitors of the plasmodial mitochondrial electron transport chain targeting Cytochrome bc1 (complex III). In general, the most potent 4-pyridones are lipophilic molecules with poor solubility in aqueous media and low oral bioavailability in pre-clinical species from the solid dosage form. The strategy of introducing polar hydroxymethyl groups has enabled us to maintain the high levels of antimalarial potency observed for other more lipophilic analogues whilst improving the solubility and the oral bioavailability in pre-clinical species. (C) 2011 Elsevier Ltd. All rights reserved.