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Published on: June 23, 2019
Synthesis and antimycobacterial evaluation of substituted pyrazinecarboxamides
Martin Dolezal1, Pavlina Cmedlova, Lukas Palek
1Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic. dolezalm@faf.cuni.cz
Abstract:
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).
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