Pharmacophore searching and QSAR analysis in the design of anticonvulsant drugs

A set a antiepileptic drugs (AED) that are active against the MES test, inc luding structures that are already in clinical use as well as the new compo unds recently designed in our lab, is analyzed in this article in relation to the requirements associated with the manifested activity, The strategy i nvolves the identification of the pharmacophoric pattern, by means of a sim ilarity analysis where the structural and electronic characteristics are co mpared, followed by a QSAR study. The latter shows the importance of the el ectronic descriptors, and points to the carbonyl group as the most relevant portion for the definition of the activity. Quantum chemical derived descr iptors give the best answer for both the similarity analysis and the statis tical fitting. (C) 2000 Elsevier Science B.V. All rights reserved.