The evaluation of the lipophilic characteristics of biologically active agents is indispensable for the rational design of ADMET-tailored structure–activity models. N
-alkoxy-1-hydroxynaphthalene-2-carboxanilides, and N
-alkoxy-2-hydroxynaphthalene-1-carboxanilides were recently reported as a series of compounds with antimycobacterial, antibacterial, and herbicidal activity. As it was found that the lipophilicity of these biologically active agents determines their activity, the hydro-lipophilic properties of all three series were investigated in this study. All 57 anilides were analyzed using the reversed-phase high-performance liquid chromatography method for the measurement of lipophilicity. 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, a range of software lipophilicity predictors for the estimation of clogP values of a set of N
-alkoxyphenylhydroxynaphthalenecarboxamides was employed and subsequently cross-compared with experimental parameters. Thus, the empirical values of lipophilicity (logk
) and the distributive parameters (π) were compared with the corresponding in silico characteristics that were calculated using alternative methods for deducing the lipophilic features. To scrutinize (dis)similarities between the derivatives, a PCA procedure was applied to visualize the major differences in the performance of molecules with respect to their lipophilic profile, molecular weight, and violations of Lipinski’s Rule of Five.
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