Faculty of Pharmacy, Charles University, Heyrovskeho 1203, Hradec Kralove 500 05, Czech Republic.
Bioorg Med Chem. 2011 Feb 15;19(4):1471-6. doi: 10.1016/j.bmc.2010.12.054. Epub 2011 Jan 1.
A series of fifteen new compounds related to pyrazinamide (PZA) were synthesized, characterized with analytical data and screened for antimycobacterial, antifungal and antibacterial activity. The series consists of 6-chloro-5-cyanopyrazine-2-carboxamide and N-substituted 6-amino-5-cyanopyrazine-2-carboxamides, derived from the previous by nucleophilic substitution with various non-aromatic amines (alkylamines, cycloalkylamines, heterocyclic amines). Some of the compounds exerted antimycobacterial activity against Mycobacterium tuberculosis equal to pyrazinamide (12.5-25 μg/mL). More importantly, 6-chloro-5-cyanopyrazine-2-carboxamide and 5-cyano-6-(heptylamino)pyrazine-2-carboxamide were active against Mycobacterium kansasii and Mycobacterium avium, which are unsusceptible to PZA. Basic structure-activity relationships are presented. Only weak antifungal and no antibacterial activity was detected.
合成了一系列与吡嗪酰胺（PZA）相关的十五种新化合物，并用分析数据进行了表征，并对其进行了抗分枝杆菌、抗真菌和抗菌活性筛选。该系列由 6-氯-5-氰基吡嗪-2-甲酰胺和 N-取代的 6-氨基-5-氰基吡嗪-2-甲酰胺组成，通过与各种非芳族胺（烷基胺、环烷基胺、杂环胺）的亲核取代反应衍生而来。一些化合物对结核分枝杆菌的抗分枝杆菌活性与吡嗪酰胺相当（12.5-25μg/mL）。更重要的是，6-氯-5-氰基吡嗪-2-甲酰胺和 5-氰基-6-（庚基氨基）吡嗪-2-甲酰胺对结核分枝杆菌和鸟分枝杆菌具有活性，而这些细菌对 PZA 不敏感。提出了基本的构效关系。仅检测到较弱的抗真菌活性，没有抗菌活性。
