A STRUCTURE-ACTIVITY RELATIONSHIP STUDY OF THIAZOLE DERIVATIVES WITH H-1-ANTIHISTAMINE ACTIVITY

作者：Brzezinska Elzbieta^*; Stolarska Justyna; Sobanska Anna

来源：Acta Poloniae Pharmaceutica, 2011, 68(5): 677-686.

• thiazole derivatives
• QSAR
• discriminant function analysis
• principal component analysis
• regression analysis
• drug design

A structure-activity relationship (QSAR) analysis of 19 thiazole derivatives with H-1-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-H-1 activity. In PCA the studied compounds were separated into two groups: group A with lower degree of H-1-antihistamine activity and group B with higher activity. The DFA showed that the parameters: alpha (polarizability), AB (distance between aliphatic and aromatic nitrogen atoms), E-b (binding energy). H-h (hydration energy), e(HOMO) (HOMO energy), and Q(Ar) are responsible for separation between compounds exhibiting higher and lower H-1-antihistamine activity. The importance of hydrophobic and steric parameters for thiazole derivatives 1-19 with H-1-antihistamine activity was established via RA. On the basis of PCA, DFA and RA methods, a prediction rule for classifying new thiazole derivatives with H-1-antihistamine activity was elaborated.

• 出版日期2011-10