Application of thin-layer chromatographic data in quantitative structure-activity relationship assay of thiazole and benzothiazole derivatives with H1-antihistamine activity.: II

Quantitative structure-activity relationship (QSAR) analysis of H-1-antihistamine activity was carried out and chromatographic data of 2-[2-(phenylamino)thiazol-4-yl]ethanamine, 2-(2-benzyl-4-thiazolyl)ethanamine, 2-(2-benzhydrylthiazol-4-yl) ethylamine derivative, and 2-(1-piperazinyl- and 2-(hexahydro-1H-1,4-diazepin-1-yl)benzothiazole derivatives were obtained. Normal-phase (NP) TLC plates (silica gel 60F(254)), impregnated with solutions of selected amino acid mixtures. na solvents as human histamine H-1-receptor (hH1R) antagonistic (L-ASP. L-Asn. L-Thr and L-Lys) were used in two developing solvents as human histamine H-1-receptor (hH1R) antagonistic interaction models. The lipophilicity data of the examined compounds were obtained and used in the QSAR assay. Using regression analysis, relationships between chromatographic and biological activity data were found. The correlations obtained in the present experiment with NP-TLC are more significant that those obtained in the experiment with RP2 TLC, because of the optimal fitting of the chromatographic system conditions to the lipophilicity of solutes. All proposed chromatographic models should facilitate pre-selection of the new drug candidates. The correlations of calculated pA(2)(H-1) values of the tested compounds predicted by the use of the best equations versus their pA(2)(H-1) obtained from the biological tests were significant (R-2=0.91-0.94). (C) 2003 Elsevier B.V. All rights reserved.