An exploratory study to investigate possible simple descriptors in order to predict relative activity of antiepileptic enaminones

Abstract

AbstractA general structure, substituent and activity relationship of the following type has been fitted to the available ED50 values of cyclic enaminone antiepileptic compounds: ${\rm ED}_{50} = f\left[ {{\rm structure,}\;{\rm substituent}} \right] = f[d, \sigma]$. In this relationship ‘structure’ was quantified by d, the distance measured between the carbonyl oxygen and the first atom of the aromatic ring. The ‘substituent’ was quantified by Hammett substituent constant: (σ). With the aid of the above function of two independent variables, a new molecular structure was predicted by extrapolation that has shown about two orders of magnitude greater activity than the most active molecule in the original set with measured ED50 values. Copyright © 2008 John Wiley & Sons, Ltd.