STRUCTURE-ACTIVITY RELATIONSHIPS OF FENAMIC ACIDS

Physicochemical properties such as the dissociation constant in Hz0 and partition coefficient with the l-octanolHzO system have been determined for a set of 3’-suhstituted fenamic acids including flufenamic and mefenamic acids. It has been found that the log KA value is linearly related with the Hammett u constants and the n value of 3’ substituents is practically identical with those derived from substituted phenols. With the use of substituent parameters, u and n, the BSA binding affinity and uncoupling activity of the acids have been analyzed. An important role of hydrophobicity is found for each of the activities. The uncoupling activity of fenamic acids is indicated to vary according to common features with other sets of uncouplers such as phenols, benzimidazoles, and methylenebisphenols, hydrophobically as well as electronically, suggesting that they interact quite similarly with the energy conservation mechanism of mitochondria.