In vitro Antifungal Activity of 5-Alkyl-6-chloropyrazine-2-carboxamides and the Corresponding Thioamides

Jana Krinková¹ (krinkova@faf.cuni.cz), Martin Doležal¹, Jiří Hartl¹, Vladimír Buchta²

¹Department of Pharmaceutical Chemistry and Drug Control,
²Department of Biological and Medical Sciences,
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic

Summary

Homolytic alkylation of 6-chloropyrazine-2-carbonitrile by alkanoic acids and subsequent partial hydrolysis afforded 5-alkyl-6-chloropyrazine-2-carboxamides, which were converted by Lawesson’s reagent into corresponding thioamides. Products were tested for their in vitro antifungal activity. The structure—activity relationships were studied. Three of the tested compounds, 6-chloro-5-butylpyrazine-2-carbothioamide, 6-chloro-5-isobutylpyrazine-2-carbothioamide, and 6-chloro-5-(1,1-dimethylethyl)-pyrazine-2-carbothioamide, were active in vitro against all eight strains tested (MIC values ranged from 62.5 to 500 µmol.dm^-3). Thioamides exerted higher antifungal activity than the corresponding amides. The values of hydrophobicity in the series of studied compounds were determined. The activity dropped or disappeared at the compounds with lower lipophilicity (log P > 2.28). Some interesting correlation between antimycobacterial and antifungal activity was found.