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

A quantitative structure-activity relationship analysis of H 1-antihistamine activity and chromatographic data of 2-[2-(phenylamino)thiazol-4-yl]ethanamine; 2-(2-benzyl-4-thiazolyl)ethanamine; 2-(2-benzhydrylthiazol-4-yl)ethylamine derivative; 2-(1-piperazinyl- and 2-(hexahydro-1H-1,4-diazepin-1-yl)benzothiazole derivatives was made. The RP2 thin-layer chromatography (TLC) plates (silica gel RP2 60F254 silanised precoated), impregnated with solutions of selected amino acid mixtures (L-Asp, L-Asn, L-Thr and L-Lys), were used in two developing solvents as hH1R antagonistic interaction models. Using regression analysis, the relationships between chromatographic and biological activity data were found. The correlations obtained in regression analysis for the examined thiazole and benzothiazole derivatives with H1-antihistamine activity [pA 2(H1)] represent their interaction with all the proposed biochromatographic models (S1-S7). Some of the calculated equations can be applied to predict the pharmacological activity of new drug candidates. The best multivariate relationships useful in predicting the pharmacological activity of thiazole and benzothiazole derivatives were obtained under the condition of experiment with RP2 TLC plates using the developing solvent acetonitrile-methanol-buffer (40:40:20, v/v). The log P values of particular compounds are extremely important for this kind of activity. © 2003 Elsevier B.V. All rights reserved.