The thin-layer chromatography technique with a micellar mobile phase was used to predict the pharmacokinetic properties of newly synthesized azaisocytosine-containing congeners that are considered as potential anti-cancer drugs. TLC RP-CN pre-coated plates were applied as the stationary phase, and buffered (pH = 7.4) 0.1 M sodium dodecyl sulphate with 20% (V/V) of tetrahydrofuran was used as the mobile phase. The quantitative structure‒activity relationships (QSARs) methodology was used to predict the compounds’ blood‒brain distribution (log BB), the unbounded fraction in the brain (fu,brain), and their binding to the human plasma proteins (log Ka,HSA). The independent variables were the chromatographic lipophilicity, polarizability, and molecular weight. The statistically significant, quantitative structure‒activity relationships that were established highlighted the significance and possibilities of the planar technique in predicting the pharmacokinetic properties of organic compounds in screening investigations. The procedure for restoring precoated plates and re-using them in chromatography studies was presented. The results confirmed the advantages of the planar chromatography technique that makes it possible to use chromatographic plates multiple times without significant deterioration of the efficiency and repeatability of the retention data.