Abstract: The series of thirteen mono-substituted 3-arylaminopyrazine-2,5-dicarbonitriles was prepared by the reaction of 3-chloropyrazine-2,5-dicarbonitrile with the appropriated anilines. The general synthetic approach of all newly synthesized compounds is presented. All the substituted 3-arylaminopyrazine-2,5-dicarbonitriles, which showed significant antifungal and antimycobacterial activity, were analyzed using the reversed phase high performance liquid chromatography (RP-HPLC) method for the lipophilicity measurement. The procedure was performed under isocratic conditions with methanol as an organic modifier in the mobile phase using end-capped non-polar C₁₈ stationary RP column. In the present study the correlation between RP-HPLC retention parameter log K (the logarithm of capacity factor K) and log P data calculated in various ways is shown. The relationships between the lipophilicity and the chemical structure of the studied compounds are discussed as well.