A structure-activity relationship study of compounds with antihistamine activity.

A structure-activity relationship (SAR) analysis of H(1)-, H(2)- and H(3)-antihistamine activity was carried out and chromatographic data of 2-[2-(phenylamino)thiazol-4-yl]ethanamine, 2-(2-benzyl-4-thiazolyl)ethanamine, 2-(2-benzhydrylthiazol4-yl)ethanamine, 2-(1-piperazinyl- and 2-(hexahydro-1H-1,4-diazepin-1-yl)benzothiazole, 2-(1-piperazinyl)benzothiazole, 2-[4-(1-alkyl)piperidinyl]benzothiazole, 2-(N,N',N'-dimethylalkyl-1,2-ethanediamino)benzothiazole, 2[1-(4-aminopiperidinyl)]benzothiazole, 2-[2-phenyl-4-thiazolyl]ethanamine derivatives and selected H(1)- and H(2)-antihistamine drugs were obtained. NP TLC and RP2 TLC plates (silica gel NP 60F(254) and silica gel RP2 60F(254) silanized precoated), impregnated with a solution of aspartic acid (L-Asp) and a solution of an analogue of aspartic acid (propionic acid), were used in two developing solvents as H(1)-, H(2)- and H(3)-antihistaminic interaction models. The lipophilicity data of the examined compounds were obtained and used in the SAR assay. Biochromatographic tests using TLC plates impregnated with solutions of asparic acid or propionic acid were found to be a source of useful data for the qualitative analysis of compounds with different structures, demonstrating activity to histamine H(1)-, H(2)- and H(3)-receptors. The four presented discriminant models based on biochromatographic studies are an efficient tool in the SAR analysis for initial prediction of compound activity direction within histamine receptors.

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 H1-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 [pA2(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.

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 H1-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 60F254), impregnated with solutions of selected amino acid mixtures (L-Asp, L-Asn, L-Thr and L-Lys) were used in two developing solvents as human histamine H1-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 pA2(H1) values of the tested compounds predicted by the use of the best equations versus their pA2(H1) obtained from the biological tests were significant (R2 = 0.91-0.94).