Molecular orbital calculations of the activities of a series of CNS drugs

Abstract

CNDO/2 molecular orbital calculations were performed on a series of twenty-nine derivatives of methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazoline). The indices which were computed were frontier electron densities, charge densities, E_HOMO, E_LUMO, the difference between E_HOMO and E_LUMO, the electrophilic superdelocalizabillty using only the HOMO and also by summation over the occupied orbitals, and the nucleophilic superdelocalizabilities using only the LUMO and by summation over the unoccupied orbitals.

Biological activity data was available from the results of nine testing procedures which examine the compounds' sedative and anticonvulsant activities. Each type of biological data was used to seek correlations with the molecular orbital. indices. Useful equations were calculated for six of the biological tests; these may prove to be useful for the prediction of new active compounds.