Antimalarial simplified 3-aryltrioxanes: synthesis and preclinical efficacy/toxicity testing in rodents.
Antimalarial simplified 3-aryltrioxanes: synthesis and preclinical efficacy/toxicity testing in rodents.
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抗疟简化 3-芳基三恶烷：啮齿动物的合成和临床前功效/毒性测试。
DOI：
10.1021/jm0102396
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发表时间：
2001
影响因子：
7.3
通讯作者：
Shapiro,TA
中科院分区：
文献类型：
--
作者：
Posner,GH;Jeon,HB;Parker,MH;Krasavin,M;Paik,IH;Shapiro,TA
本文介绍了一种合理设计、简化的3-芳基三恶烷的五步化学合成法。该合成方案的一个值得注意的特征是使用空气而不是昂贵的分子氧作为三恶烷8a中的临界过氧化物单元的来源。这种简化的缩醛三恶烷羧酸8是热稳定的，并且它甚至在40 °C和pH 7.4下在水中水解稳定至少7天。对这种水溶性合成三恶烷8在啮齿动物中的临床前评价显示，它至少具有与水溶性半合成三恶烷青蒿酸一样好的治疗指数（功效/毒性）（5）。
A streamlined five-step chemical synthesis of rationally designed, simplified 3-aryltrioxane8ais described. A noteworthy feature of this synthetic scheme is use of air rather than expensive molecular oxygen as the source of the pharmacologically critical peroxide unit in trioxane8a. This simplified acetal trioxane carboxylic acid8ais thermally stable, and it is hydrolytically stable in water even at 40 °C and pH 7.4 for at least 7 days. Preclinical evaluation of this water-soluble synthetic trioxane8ain rodents shows it to have at least as good a therapeutic index (efficacy/toxicity) as that of water-soluble semisynthetic trioxane artelinic acid (5).