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).
Brzezińsk
Elzbieta
E
Department of Analytical Chemistry, Medical University of Lódź, Ul. Muszyńskiego 1, 90-151 Lodz, Poland. ebrzezinska@pharm.am.lodz.pl
Kośka
Grazyna
G
Kłimczak
Alicja
A
D052160:Benzothiazoles; D002855:Chromatography, Thin Layer / Q000379:methods*; D006634:Histamine H1 Antagonists / Q000032:analysis*; D021281:Quantitative Structure-Activity Relationship; D013844:Thiazoles / Q000032:analysis*
D052160:Benzothiazoles; D006634:Histamine H1 Antagonists; D013844:Thiazoles; C005465:benzothiazole