Synthesis of arylacetic acids and their effect on activation of fibrinolysis. Quantitative relations between structure and biological activity

Abstract

A series of arylacetic acids, III, has been prepared and evaluated for activation of fibrinolysis and inhibition of heat-denaturation of serum albumin. regression analysis revealed that either activity was influenced mainly by lipophilicity of the aromatic substituents. The graph showing activation of fibrinolysis by acids III takes a linear course up to a maximum, followed by a step decrease. Also included in the series are p-benzyloxy derivatives of the arylacetic acids. Their lipophilicity has been evaluated by thin-layer chromatography, the method of reversed phase being employed. However, the lipophilicity parameters thus obtained fail to describe the hydrophobic bonding of these derivatives to the active site; tabulated values of the parameter π were better in this respect.