Substituted pyrazinecarboxamides: Synthesis and biological evaluation

Abstract

Condensation of the corresponding chlorides of some substituted pyrazine-2-carboxylic acids (pyrazine-2-carboxylic acid, 6-chloropyrazine-2- carboxylic acid, 5-tertbutylpyrazine-2-carboxylic acid or 5-tert-butyl-6- chloropyrazine-2-carboxylic acid) with various ring-substituted aminothiazoles or anilines yielded a series of amides. The syntheses, analytical and spectroscopic data of thirty newly prepared compounds are presented. Structure-activity relationships between the chemical structures and the antimycobacterial, antifungal and photosynthesis-inhibiting activity of the evaluated compounds are discussed. 3,5-Bromo-4-hydroxyphenyl derivatives of substituted pyrazinecarboxylic acid, 16-18, have shown the highest activity against Mycobacterium tuberculosis H37Rv (54-72% inhibition). The highest antifungal effect against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for 5-tert-butyl-6-chloro-N-(4- methyl-1,3-thiazol-2-yl)pyrazine-2-carboxamide (8, MIC = 31.25 μmol·mL-1). The most active inhibitors of oxygen evolution rate in spinach chloroplasts were the compounds 5-tert-butyl-6-chloro-N-(5- bromo-2-hydroxyphenyl)-pyrazine-2-carboxamide (27, IC50 = 41.9 μmol·L-1) and 5-tert-butyl-6-chloro-N-(1,3-thiazol-2-yl)- pyrazine-2-carboxamide (4, IC50 = 49.5 μmol·L -1). © 2006 by MDPI.