The synthesis of arylpropionic acids and the quantitative relationship between the structure and the activation of fibrinolysis

Abstract

A number of substituted 2-arylpropionic (IV) and 3-arylpropionic (V) acids were prepared and their activity in the activation of fibrinolysis and the inhibition of heat denaturation of serum albumin was evaluated. The results were worked up using the method of regression analysis. From the regression equations obtained it may be considered that both activities are affected mainly by the lipophilicity of the aromatic substituents. The effect of the branching in the connecting chain between the carboxyl group and the aromatic ring is negligible in both activities. The linear dependence of the fibrinolytic capacity on lipophilicity is in both series of acids, IV and V, characterized by a distinct decrease in activity, following the attainment of the optimum value of lipophilicity. In the series of cinnamic acids (VI) regression equations concerning the inhibition of the denaturation of serum albumin and the activation of fibrinolysis were also calculated, showing a linear dependence of these activities on the lipophilicity of the varying substituents R and X. Summary regression equations were derived for both activities in the whole set of acids I-VI. Both the inhibition of the denaturation of serum albumin, and the activation of fibrinolysis depends on the lipophilicity of the mentioned acids exclusively. The modification of the connecting chain between the carboxyl group and the aromatic ring affects both activities primarily by the corresponding change in lipophilicity.