Brzezińska Elzbieta, Kośka Grazyna, Walczyński Krzysztof
Department of Analytical Chemistry, Medical University of Lódź, Muszyńskiego 1, 90-151 Lódź, Poland.
J Chromatogr A. 2003 Jul 25;1007(1-2):145-55. doi: 10.1016/s0021-9673(03)00951-8.
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.
对2-[2-(苯胺基)噻唑-4-基]乙胺、2-(2-苄基-4-噻唑基)乙胺、2-(2-二苯甲基噻唑-4-基)乙胺衍生物、2-(1-哌嗪基-和2-(六氢-1H-1,4-二氮杂卓-1-基)苯并噻唑衍生物的H1-抗组胺活性与色谱数据进行了定量构效关系分析。使用浸渍有选定氨基酸混合物（L-天冬氨酸、L-天冬酰胺、L-苏氨酸和L-赖氨酸）溶液的RP2薄层色谱（TLC）板（硅胶RP2 60F254硅烷化预涂板），在两种展开溶剂中作为hH1R拮抗相互作用模型使用。通过回归分析，发现了色谱数据与生物活性数据之间的关系。在所研究的具有H1-抗组胺活性[pA2(H1)]的噻唑和苯并噻唑衍生物的回归分析中获得的相关性代表了它们与所有提出的生物色谱模型（S1-S7）的相互作用。一些计算出的方程可用于预测新药候选物的药理活性。在使用展开溶剂乙腈-甲醇-缓冲液（40:40:20，v/v）的RP2 TLC板实验条件下，获得了用于预测噻唑和苯并噻唑衍生物药理活性的最佳多变量关系。特定化合物的log P值对这种活性极为重要。
