RT Journal Article SR Electronic T1 Physicochemical Properties and Uncoupling Activity of 3'-Substituted Analogues of N-Phenylanthranilic Acid JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 95 OP 103 VO 8 IS 1 A1 HIROSHI TERADA A1 SABURO MURAOKA YR 1972 UL http://molpharm.aspetjournals.org/content/8/1/95.abstract AB The relationship between the physicochemical properties and uncoupling activity of flufenamic acid [N-(3'-trifluoromethylphenyl)anthranilic acid] and its structural analogues, which vary in position 3' of the phenyl ring, has been investigated. Some of these compounds are known to be potent anti-inflammatory agents. Their physicochemical properties were compared with their uncoupling activities, measured as their effects on State 4 respiration and on the ATP-Pi exchange reaction of rat liver mitochondria. The partition coefficients, determined in n-heptane—H2O, n-hexane—H2O, and chloroform—H2O at pH 7, increased with introduction of hydrophobic groups such as -CF3, -CH3, and -C6H5 into N-phenylanthranilic acid, and decreased with introduction of hydrophilic groups such as -OH, -NH2, and -SO3H. Compounds with large partition coefficients had high uncoupling activity, and this correlation was highest in the chloroform—H2O system. The formation of a dimer in the organic solvent phase was strongly suggested in chloroform, but not in n-hexane or n-heptane, with compounds possessing -H, -CF3, -CH3, or -NO2 at position 3'. Higher uncoupling activity was correlated with larger pKa values. Also, an important role of the hydrophobic nature of the acids with respect to uncoupling was confirmed for compounds that had similar ionization constants but different uncoupling activities. ACKNOWLEDGMENTS The authors are indebted to Misses T. Jinnai and K. Hirata for expert technical assistance.