Collect. Czech. Chem. Commun. 1982, 47, 2514-2524

Benzyloxyarylaliphatic acids: Synthesis and quantitative relations between structure and antiinflammatory activity

Miroslav Kuchařa, Václav Rejholeca, Bohumila Brunováa, Jaroslava Grimováa, Oluše Matoušováa, Oldřich Němečeka and Hana Čepelákováb

a Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3
b Faculty Hospital, Charles University, 300 00 Plzeň


The paper describes synthesis of substituted benzyloxyarylaliphatic acids, I-V, and their efficacy in stabilization the erythrocyte membrane against hypotonic haemolysis and their antiinflammatory effect in inhibition of the kaolin oedema. The quantitative relations between these efficacies and the physico-chemical and structural parameters of the acids have been analysed. The two activities depend on the overall lipophilicity and acidity of the acids. In the investigated range of lipophilicity the dependence of the antiinflammatory effect on lipophilicity had a parabolic course, whereas in stabilization of the erythrocyte membrane this dependence was linear. In either case the efficacy was suppressed by extending the connecting chain between the carboxyl and the aromatic ring. Regression analysis suggests that in the group of benzyloxyarylaliphatic acids it is not possible to prepare compounds more effective than 3-chloro-4-benzyloxyphenylacetic acid (benzofenac, Ia) and its 2-methyl analogue IIa.