Quantitative relations between structure and activation of fibrinolysis in selected series of arylaliphatic acids

Abstract

The paper describes the reaction of arylacetones IX with triethyl phosphonoacetate, producing esters of 4-aryl-3-methyl-2-butenoic acid, X, and 4-aryl-3-methyl-3-butenoic acid, X'. Their hydrolysis gave a mixture of the isomeric acids I and I', whose composition was investigated by 1H NMR spectra. Also prepared were 3-methyl-3-phenyl-2-propenoic acids, II, 2-aryl-2-hydroxypropanoic acids, IV, and substituted α-benzyloxyphenylacetic acids, V. These acids, along with aryloxoaliphatic acids III, were investigated for efficacy in activation of fibrinolysis. The lipophilicites of the acids studied were determined either through the partition coefficients (acids Ia and IIa), using a system n-octanol-water (pH 3.5) or by partition chromatography. The experimental values of log Pwere compared with those calculated from the fragmental constants f and the parameters π. With the acids V the decrease in lipophilicity was similar to that observed with arylalkoxyaliphatic acids. With the acids, I, I' and II the fibrinolytic capacity was linearly proportional to lipophilicity. Although we evaluated fibrinolytic capacity of mixtures of the acids I and I', the linear relation was in agreement with that derived previously for a group of arylaliphatic acids. The presence of a functional group on the connecting chain in the acids III and IV had a negative effect on the fibrinolytic capacity. The decrease in fibrinolytic capacity might be due the functional groups being capable of forming hydrogen bonds.