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.

Application of the statistical methods in systematic structure-activity relationship analysis of thiazole, benzothiazole and tetrahydroisoquinoline derivatives with biological activity.

The procedure of initial studies to evaluate usefulness of the collected data for performing efficient QSAR analysis of any group of pharmacologically active substances was worked out. Structure-Activity Relationship (SAR) study on the thiazole derivatives with H1-antihistamine activity, the benzothiazole derivatives with H3-antihistamine activity and tetrahydroisoquinoline (TIQ) derivatives with beta 2-adrenolytic activity, was performed by means of Factor Analysis (FA) and Regression Analysis (RA). The potential drug forms (neutral or ionic) in the particular physiological environment (pH) were used to examine the actual properties of the drug in its action place. It was determined based on their pKa values. The usefulness of the group cases selected for QSAR studies was evaluated, based on the relationship between their structural variability and the variability of their specific biological activity.

The chromatographic data in QSAR assay of TIQs derivatives with beta2-adrenergic activity.

We performed QSAR analysis of beta2-adrenergic activity and chromatographic data of 4,6,8-trihydroxy-, 6,7-dihydroxy- and 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives. TLC plates (silica gel NP 60F(254) and silica gel RP2 60F(254) silanised precoated), impregnated with solutions of analogues of the selected amino acids were used as beta2-agonistic and antagonistic interaction models. QSAR analysis of the beta2-adrenergic activity and the chromatographic data of the solutes were made. A correlation between biological data and behaviour of the examined compounds in a chromatographic modifiable environment (S1-S3) was investigated by the linear regression analysis method.