Computer-aided investigation of the structure-activity relationships of benzodiazepine derivatives at diazepam-sensitive receptors

Abstract

The series of compounds investigated includes 23 benzodiazepine derivatives, some of which demonstrate anxiolytic, anticonvulsant and sedative-hypnotic properties. The series was partitioned into two classes of active and inactive compounds. Preliminary calculations of the electronic and geometry parameters were carried out to form the so-called electron-topologic matrices of contiguity (ETMC) for each compound in the series. By comparing the matrices, the molecular fragment responsible for the desired activity has been found in all ETMC of the active compounds as a common submatrix, and is called the activity feature. A submatrix of the molecular fragment that is the feature of inactivity has been revealed, too. The properties of the two features have been studied and used as rules to predict the desired activity in a series of new compounds. (C) 1999 Elsevier Science B.V. All rights reserved.