Benzodiazepine stereochemistry: crystal structures of the diazepam antagonist Ro 15-1788 and the anomalous benzodiazepine Ro 5-4864

Abstract

The crystal and molecular structures of the benzodiazepine antagonist Ro 15-1788, and of Ro 5-4864, a diazepam derivative with low affinity for central benzodiazepine receptors, have been determined. Stereochemical comparisons with diazepam have resulted in the conclusion that the steric bulk of the 4′-chlorine atom alone is responsible for the lowered activity of Ro 5-4864, and have suggested possible structural reasons for the antagonist/weak agonist activities of Ro 15-1788.