Theoretical and Chromatographic Studies to Determine Selected Physicochemical Parameters of 8-Trifluoromethylquinobenzothiazines as Potential Bioactive Compounds

Background: Chemical modification of the phenothiazine structure enables the synthesis of promising molecules that are potential candidates for new drugs with a broad spectrum of biological activity. Both computational and experimental methods play a crucial role in the preliminary study of new bioactive compounds, serving to determine various physicochemical properties that influence a compound’s ADMET profile, including its lipophilicity. Objectives: The main objective of this study was to conduct research combining theoretical and chromatographic methods for the rapid and efficient assessment of lipophilicity descriptors and other physicochemical parameters—crucial for ADMET processes—for a series of 13 newly synthesized 8-trifluoromethylquinobenzothiazines. Methods: Experimental lipophilicity descriptor values for the previously synthesized compounds (1–13) were determined according to the methodology of Soczewiński and Wachtmeister, using reversed-phase thin-layer chromatography (RP-TLC) on RP-2F254, RP-8F254, and RP-18F254 plates with the following mobile phases: acetone–TRIS buffer (pH 7.4), propan-2ol–TRIS buffer (pH 7.4), and 1,4-dioxane–TRIS buffer (pH 7.4). Theoretical values of the lipophilicity parameter (logP) were predicted using various computational tools based on SMILES formula. Furthermore, selected topological indices—such as Pyka (A, 0B, 1B), Wiener (W), Rouvray–Crafford (R), Gutman (M, Mν), and Randić (0χ, 1χ, 0χν, 1χν)—were calculated for the studied compounds for the first time. Results: The lipophilicity parameters of the 13 studied compounds—both experimentally determined (as RMW) and calculated—were subjected to correlation analysis with topological index values and other factors determining biological activity. The resulting QSPR (quantitative structure–property relationship) models—presented as linear equations linking topological indices to RMW or logP values, as well as to other physicochemical parameters of the compounds under study—were verified using leave-one-out cross-validation. Conclusions: Cross-validation of these relationships between the topological index (TI) and the property (P) of studied compounds enabled the selection of the most promising QSPR models, which hold exploratory significance and may, in the future, play an important role in further structure–properties studies concerning this type of derivative.