On the quantitative relations between structure and antiaggregation activity of ω-aryl-ω-oxoalkanoic acids

Abstract

A series of ω-aryl-ω-oxoalkanoic acids, I-IV, has been prepared and investigated for dissociation constants in 80% methylcellosolve, retention characteristics in thin-layer partition chromatography and partition coefficients P in the system octanol-water. Also evaluated were their anti-inflammatory efficacy and inhibitory effect on the platelet aggregation induced by collagen. Analysing the relations between structure and antiaggregation effect, we obtained a non-linear, quadratic dependence of this effect on lipophilicity, the optimum being at log P = 3. The antiaggregation effect increased with shortening the chain between the carbonyl and the carboxyl, and with increasing acidity. It was also diminished by the presence of a methyl group on the interlinking chain. To assess the role of lipophilicity we used the RM values of partition chromatography. The relation between anti-inflammatory efficacy and structure was assessed only qualitatively. In this aspect, too, the nature of the chain between the carbonyl and carboxyl proved to have a marked influence. The anti-inflammatory activity proved considerably enhanced by the presence of another aromatic ring in ω-oxoalkanoic acids derived from biphenyl.