A structure-activity relationship study of thiazole derivatives with H1-antihistamine activity.

A structure-activity relationship (QSAR) analysis of 19 thiazole derivatives with H1-antihistamine activity was carried out. The semi-empirical method AMI was employed to calculate a set of physicochemical parameters for investigated compounds. The principal component analysis (PCA), discriminant function analysis (DFA) and regression analysis (RA) were employed to reduce dimensionality and investigate which subset of variables is effective for classifying the thiazole derivatives according to their degree of anti-H1 activity. In PCA the studied compounds were separated into two groups: group A with lower degree of H,-antihistamine activity and group B with higher activity. The DFA showed that the parameters: alpha (polarizability), AB (distance between aliphatic and aromatic nitrogen atoms), Eb (binding energy), Hh (hydration energy), eHOMO (HOMO energy), and QAr are responsible for separation between compounds exhibiting higher and lower H1-antihistamine activity. The importance of hydrophobic and steric parameters for thiazole derivatives 1-19 with HL-antihistamine activity was established via RA. On the basis of PCA, DFA and RA methods, a prediction rule for classifying new thiazole derivatives with H1-antihistamine activity was elaborated.