Antimycobacterial Evaluation of some Anilides of Pyrazine-2-carboxylic Acid

Martin Doležal (dolezalm@faf.cuni.cz), Jiří Hartl, Miroslav Miletín

Department of Pharmaceutical Chemistry and Drug Control, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic

Summary

Condensation of chlorides of substituted pyrazine-2-carboxylic acids with ring substituted anilines yielded a series of 12 anilides of 6-chloropyrazine-2-carboxylic, 5-(1,1-dimethylethyl)pyrazine-2-carboxylic or 6-chloro-5-(1,1-dimethylethyl)pyrazine-2-carboxylic acids. Products were tested for their antimycobacterial activity. The structure—activity relationships were studied. The values of hydrophobicity in the series of studied compounds were determined. Three of the tested compounds were quite active in vitro against M. tuberculosis (> 50% inhibition). 6-Chloro-5-(1,1-dimethylethyl)pyrazine-2-carboxylic acid 4-hydroxy-anilide (97% inhibition) was the most active compound. The activity dropped or disappeared either at the compounds with lower lipophilicity (log P > 2.00) or at the compounds with higher lipophilicity parameters (log P < 3.80).