Collect. Czech. Chem. Commun. 1990, 55, 296-306

Use of QSAR in design of antiinflammatory fluorinated arylalkanoic acids

Miroslav Kuchař, Jaroslava Grimová, Václav Rejholec, Hana Tomková, Magda Jelínková and Jiří Holubek

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


A series of 3-fluro-4-alkoxyphenylalkanoic acids III was synthetized and their antiinflammatory activity and fibrinolytic capacity was evaluated. The suitable fluorinated derivative with better pharmacological profile than 3-chloro-4-benzyloxyphenylacetic acid (benzofenac) was selected. Experimental, biological activities of acids III were compared with those calculated by introducing the physico-chemical parameters into the formerly derived regression equations. Good coincidence was found out, as well as similarity of the regression derived for the original series of acids extended by the acids III. Lipophilicity of the acids under study was evaluated by partition thin-layer chromatography; the values of log P of benzyloxy derivatives IIIc-IIIf were lower than tabulated values - probably due to the intramolecular hydrophobic interactions of aromatic nuclei.