Collection of Czechoslovak Chemical Communications - digital archive 

Abstract

A series of substituted cyclohexylacetic acids I has been obtained by hydrogenation of the unsaturated analogues II and III. Esters of these analogues were prepared by the Horner-Wittig reaction of the corresponding cyclohexanones IV and/or 2-cyclohexenones V with triethyl phosphonoacetate. These esters were obtained in two isomeric forms (Z and E), differing in the double bond in the exo-position. The derivatives with a substituent in the 2-position exhibited a partial shift of the double bond to the cyclohexane ring; this shift was especially marked in the 2-phenyl derivative. With the acids I-III, activation of fibrinolysis was assessed by the hanging clot method; the anti-inflammatory effect was assessed by inhibition of two experimental model inflammations. The regression equation relating fibrinolytic capacity to lipophilicity was a quadratic one, the logarithm of optimum lipophilicity being log P_opt = 5.55. A qualitative assessment of the anti-inflammatory effect in relation to lipophilicity suggests that log P_opt is probably higher than with arylaliphatic acids. These acids seem to have an active site different from that of the acids I-III.