Čes. slov. farm. 1999, 48(2):80-86

The Relationship of the Structure, Physico-Chemical Properties and Local Anaesthetic Activity in a Group of 1-Methyl-2-piperidinoethylester of 2-, 3- and 4-Alkoxyphenylcarbamic Acids

M. Pokorná¹, J. Čižmárik¹, E. Sedlárová¹, E. Račanská²

¹ Katedra farmaceutickej chémie Farmaceutickej fakulty Univerzity Komenského, Bratislava

² Katedra farmakológie a toxikológie Farmaceutickej fakulty Univerzity Komenského, Bratislava

Within the framework of a systematic study of phenylcarbamic acid derivatives with local anaes-thetic effects, a series of 1-methyl-2-piperidinoethylesters of 2-, 3- and 4-alkoxy(methoxy to decyloxy)phenylcarbamic acids and an unsubstituted derivative, i.e. 1-methyl-2-piperidinoethylester ofphenylcarbamic acid, were prepared. In the prepared series of compounds, the mutual relationshipof the surface local anaesthetic activity and some physical and physico-chemical parameters (g, pKa,pH of turbidity, log P, p, RMr, log k') was studied and quantified by the method of QSAR analysis.The steric constants L and B4, molar refraction (MR), valence indices of molecular connectivity (1 c v),the number of carbons of the alkoxysubstituent (Cx) and molecular mass (Mr) were also correlated.The study has revealed that there exists a linear relation between the number of the carbons of the alkoxysubstituent (Cx), tabulated or calculated values (Mr, L, B4, MR, 1 c v ) and experimentallyobtained physico-chemical parameters (RMr, log P, p, log k', pH of turbidity, pKa).

Keywords: 1-methyl-2-piperidinoethylester of alkoxyphenylcarbamic acids; local anaesthetic activity; structure-activity relationship

Published: February 1, 1999  Show citation