Study of anaesthetical activity of alkoxyphenylcarbamic acid esters using statistical methods

Tatiana Ďurčeková,Jozef Čižmárik,Jozef Lehotay,Ján Mocák

doi:10.36547/nbc.1368

Abstract

Anaesthetical activity of 113 morpholinoethyl-, piperidinoethyl-, piperidinopropyl- and azepanoethyl- ester derivatives of alkoxyphenylcarbamic acid was characterized by several chemometrical techniques. The surface anaesthetical activity, A, and the infiltration anaesthetical activity, B, were correlated to lipophilicity, (expressed by the logarithm of the HPLC retention factor, log k), the length of the side alkoxy chain (represented by the number n of carbon atoms), molar mass M as well as the ester type. Principal component analysis and cluster analysis were used for predicting both types of the anaesthetic activity of the alkoxyphenylcarbamic acid esters.

Highlights

The prediction of the compound property is the basic problem of the quantitative studies of the relationships structure - activity
The correlation analysis shows the measure of correlation expressed by the pair (Pearson) correlation coefficients between all pairs of the studied variables
Cluster analysis is represented by a dendrogram showing the distances among the objects or the used variables

Summary

Introduction

The prediction of the compound property is the basic problem of the quantitative studies of the relationships structure - activity. The basic assumption is that the compounds with similar structure dispose of a similar biological activity (KUCHAŘ, REJHOLEC, 1987), as it was stated in a similar anaesthetics study of HATRÍK et al, 1995). After discovery of a biologically active compound with a new structure, the phase of the activity optimization is commonly characterized by varying the basic structure in order to achieve the maximal biological activity (HATRÍK et al, 1995a). In this paper an attempt is made to correlate both types of the anaesthetical activity to the chemical shifts in the 1H NMR and 13C NMR spectra of the examinated compounds. When simulated chemical shifts are used it is possible to omit laborious chemical synthesis – at least in the first phase of such study

Experimental

Results and discussion

C3 C5 H1 C10 HCH3 logA logk M n C12 H12

H1 C5 C12 H12 q H C2 C4 C6 H2 C8