Seydel J K, Schaper K J, Wempe E, Cordes H P
J Med Chem. 1976 Apr;19(4):483-92. doi: 10.1021/jm00226a007.
Quantitative structure-activity studies have been performed for a series of 2-substituted isonicotinic acid hydrazides by correlating electronic, steric, and lipophilic properties of the substituents with the biological activity date (MIC) from serial dilution tests with Mycobacterium tuberculosis (strain H 37 Rv). The reaction rates for the quaternization of 2-substituted pyridines with methyl iodide were also determined. The rate constants show a similar dependence on the steric and electronic effects of the substituents as the antibacterial activities of the corresponding pyridine-4-carboxylic acid hydrazides. The obtained correlations give evidence that the reactivity of the pyridine nitrogen atom is essential for the biological activity of 2-substituted isonicotinic acid hydrazides and seem to support the hypothesis that isonicotinic acid derivatives are incorporated into an NAD analogue.
通过将取代基的电子、空间和脂溶性性质与来自结核分枝杆菌（H 37 Rv菌株）系列稀释试验的生物活性数据（MIC）相关联，对一系列2-取代异烟酸酰肼进行了定量构效关系研究。还测定了2-取代吡啶与甲基碘季铵化的反应速率。速率常数对取代基的空间和电子效应的依赖性与相应吡啶-4-羧酸酰肼的抗菌活性相似。所得到的相关性证明吡啶氮原子的反应性对于2-取代异烟酸酰肼的生物活性至关重要，并且似乎支持异烟酸衍生物被并入NAD类似物的假说。
