Quantitative structure-activity relationships. Antiinflammatory activity of salicylic acid derivatives

A series of 28 substituted salicylic acids possessing antiinflammatory property is investigated for structure-activity relationships in light of the linear free energy related (LFER) and Fujita-Ban models. The Fujita-Ban group contributions have been calculated for 11 different substituents on the parent ring. It is observed that among these only phenyl group at position 5 increases the activity. The activity is found to increase further if electron withdrawing groups are attached to this phenyl substituent. The LFER analysis indicates that the electronic and partitioning effects of the substituents are important factors influencing the antiinflammatory activity. A statistically significant relationship with a correlation coefficient of the order of 0.9 explaining 71% of the variance is obtained using these substituent constants.