A series of seven (2E)-3-(3,4-dichlorophenyl)-N-arylprop-2-enamide were prepared. Six compounds from this limited set were mono- and di-chlorinated not only on the aromatic ring of acid but also on the anilide ring. The compounds have been proposed as potential anti-infective, anti-inflammatory and anti-cancer agents. Since lipophilicity significantly affects the biological activities and pharmacokinetic profile of the compounds, the hydro-lipophilic properties of these new highly chlorinated compounds were experimentally studied. At the same time, the overall ADMET profiles of the compounds were investigated if they comply with the Lipinski's Rule of Five and thus meet the qualitative concepts for the new bioactive molecules to be "druglikeness". All the discussed compounds were analysed using the reversed-phase high performance liquid chromatography method. The procedure was performed under isocratic conditions with methanol as an organic modifier in the mobile phase using an end-capped non-polar C₁₈ stationary reversed-phase column. In the present study, the structure-lipophilicity relationships of the studied compounds are discussed.