Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic.
Bioorg Med Chem Lett. 2012 Feb 15;22(4):1598-601. doi: 10.1016/j.bmcl.2011.12.129. Epub 2012 Jan 3.
A series of 14 new compounds related to pyrazinamide were synthesized, characterized with analytical data and screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii and two types of Mycobacterium avium. The series comprised of N-substituted 3-aminopyrazine-2,5-dicarbonitriles derived from 3-chloropyrazine-2,5-dicarbonitrile by nucleophilic substitution of chlorine by various non-aromatic amines (alkylamines, cycloalkylamines and heterocyclic amines). Noteworthy antimycobacterial activity against M. tuberculosis was found among the alkylamino derivatives, for example, 3-(heptylamino)pyrazine-2,5-dicarbonitrile inhibited M. tuberculosis at MIC=51 μmol/L. 3-(Hexylamino)pyrazine-2,5-dicarbonitrile inhibited M. kansasii at MIC=218 μmol/L. Basic structure-activity relationships are discussed. A comparison between calculated and experimentally determined lipophilicity parameters within the series is included.
合成了一系列与吡嗪酰胺有关的 14 种新化合物，并用分析数据进行了表征，并对其进行了体外抗结核分枝杆菌、堪萨斯分枝杆菌和两种鸟分枝杆菌的活性筛选。该系列由 3-氯吡嗪-2,5-二腈通过各种非芳族胺（烷基胺、环烷基胺和杂环胺）的亲核取代反应衍生而来的 N-取代 3-氨基吡嗪-2,5-二腈组成。在烷基氨基衍生物中发现了对结核分枝杆菌有显著的抗结核活性，例如，3-（庚氨基）吡嗪-2,5-二腈在 MIC=51μmol/L 时抑制结核分枝杆菌。3-（己氨基）吡嗪-2,5-二腈在 MIC=218μmol/L 时抑制堪萨斯分枝杆菌。讨论了基本的构效关系。还包括了该系列中计算和实验确定的亲脂性参数之间的比较。
