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An exploratory study to investigate possible simple descriptors in order to predict relative activity of antiepileptic enaminones
Author(s) -
Martinez J. C. Garro,
Andrada M. F.,
Estrada M. R.,
Castro E. A.,
Zamarbide G. N.,
Mucsi Z.,
Csizmadia I. G.
Publication year - 2008
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.1365
Subject(s) - substituent , chemistry , extrapolation , ring (chemistry) , molecule , computational chemistry , stereochemistry , sigma , quantitative structure–activity relationship , oxygen atom , organic chemistry , quantum mechanics , mathematics , mathematical analysis , physics
Abstract A general structure, substituent and activity relationship of the following type has been fitted to the available ED 50 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 ED 50 values. Copyright © 2008 John Wiley & Sons, Ltd.