Charles University, Faculty of Pharmacy, Department of Inorganic and Organic Chemistry, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
Eur J Med Chem. 2011 Dec;46(12):5902-9. doi: 10.1016/j.ejmech.2011.09.054. Epub 2011 Oct 13.
A series of new isoniazid hydrazones was synthesized by two procedures. In the first isoniazid was activated with diethoxymethyl acetate and condensed with the appropriate anilines. Alternatively, substituted anilines were activated by diethoxymethyl acetate and subsequently condensed with isoniazid. NMR study confirmed that both synthetic approaches gave the same tautomer. All compounds were screened for in vitro antimycobacterial activity. Most of them exhibited the same activity against Mycobacterium tuberculosis (MIC 1 μmol L(-1)) as isoniazid (INH), better activity against Mycobacterium kansasii 325/80 (MIC 0.125-0.250 μmol L(-1)), high value of selectivity index (SI) and IC(50) between 0.0218 and 0.326 mmol L(-1). Compound 2o with the best SI was used as a model compound for the stability test and was found to be stable at neutral pH, but under acidic conditions it slowly hydrolysed.
通过两种方法合成了一系列新的异烟肼腙。第一种方法是用二乙氧基甲缩醛使异烟肼活化，然后与合适的苯胺缩合。或者，用二乙氧基甲缩醛使取代的苯胺活化，然后与异烟肼缩合。NMR 研究证实这两种合成方法得到的是相同的互变异构体。所有化合物都进行了体外抗分枝杆菌活性筛选。它们大多数对结核分枝杆菌（MIC 1 μmol L(-1))的活性与异烟肼（INH）相同，对堪萨斯分枝杆菌 325/80 的活性更好（MIC 0.125-0.250 μmol L(-1))，选择性指数（SI）和 IC(50)值很高，范围在 0.0218 到 0.326 mmol L(-1)之间。具有最佳 SI 的化合物 2o 被用作稳定性测试的模型化合物，发现它在中性 pH 值下稳定，但在酸性条件下会缓慢水解。
