Dolezal Martin, Cmedlova Pavlina, Palek Lukas, Vinsova Jarmila, Kunes Jiri, Buchta Vladimir, Jampilek Josef, Kralova Katarina
Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
Eur J Med Chem. 2008 May;43(5):1105-13. doi: 10.1016/j.ejmech.2007.07.013. Epub 2007 Aug 2.
Unsubstituted, halogenated and/or alkylated pyrazine-2-carboxylic acid amides connected via -CONH- bridge with substituted anilines were synthesized using currently known synthetic pathways. The synthetic approach, analytical, spectroscopic, lipophilicity and biological data of 20 newly synthesized compounds are presented. Structure-activity relationships among the chemical structures, the antimycobacterial, antifungal, photosynthesis inhibiting and antialgal activity of the evaluated substituted N-phenylpyrazine-2-carboxamides are discussed. 5-tert-Butyl-6-chloro-N-(3-trifluoromethylphenyl)pyrazine-2-carboxamide (19) has shown the highest activity against Mycobacterium tuberculosis H(37)Rv (MIC=3.13 microg/mL). The highest antifungal effect against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for N-(3-trifluoromethylphenyl)pyrazine-2-carboxamide (14, MIC=62.5 micromol/mL). The highest reduction of chlorophyll content in Chlorella vulgaris was found for pyrazine-2-carboxylic acid (3-trifluoromethylphenyl)amide (9, IC(50)=12.1 micromol/L).
通过 -CONH- 桥与取代苯胺相连的未取代、卤代和/或烷基化的吡嗪 -2- 羧酸酰胺是利用目前已知的合成途径合成的。本文介绍了 20 种新合成化合物的合成方法、分析、光谱、亲脂性和生物学数据。讨论了所评估的取代 N-苯基吡嗪 -2- 甲酰胺的化学结构之间的构效关系、抗分枝杆菌、抗真菌、光合作用抑制和抗藻活性。5-叔丁基-6-氯-N-(3-三氟甲基苯基)吡嗪-2-甲酰胺(19)对结核分枝杆菌H(37)Rv显示出最高活性(MIC = 3.13微克/毫升)。对于N-(3-三氟甲基苯基)吡嗪-2-甲酰胺(14，MIC = 62.5微摩尔/毫升)，发现对所测试的最敏感真菌菌株须癣毛癣菌具有最高的抗真菌效果。对于吡嗪-2-羧酸(3-三氟甲基苯基)酰胺(9，IC(50)= 12.1微摩尔/升)，发现对普通小球藻叶绿素含量的降低作用最大。
