Structure-activity relationships for non-congeneric structures. Application of substructural balance method for antiallergic activity.

ABSTRACT

This paper presents a new research method of structure-activity relationships (SAR) based on the concept of substructural balance. By using antiallergic activity (PCA, rat, iv) of a non-congeneric set of 267 structures, the structural feature of active group is expressed in terms of substructural balance. Each structure was expressed with 100 new substructures and the number of each substructure in a molecule was counted. The substructural balance was expressed as their ratio. Structures were classified into three groups based on their potencies (ED50), active (44), median (33) and inactive (190) group. Using two substructural ratios, 80.53% of inactive and 57.58% of median structures were excluded from those that were active. Common features of active structures were shown as a zone indicating the optimal ranges of two substructural ratios. Two substructural ratios were determined out of 4950 substructural ratios, all possible combinations of 100 substructures (100C2), by selecting the greatest discriminatory power of inactive from active structures. The substructures used in this work include the number of bonds comprising of the longest conjugate system, the number of skeletal atoms and the numbers of electron-donor pairs at certain distances in the molecule.