Clobazam: chemical aspects of the 1,4 and 1,5-benzodiazepines

Abstract

1 The structures and chemistry of the 1,4- and 1,5-benzodiazepines are compared. These two groups of drugs differ in respect to basicity, lipophilicity and electronic charge distribution. 2 The 1,4-benzodiazepine diazepam has a weakly basic imine group in contrast to the acid methylene protons of clobazam. 3 The imine function of diazepam is more lipophilic than the carboxamide group of clobazam with its rather hydrophilic character. 4 Diazepam and clobazam differ in electronic charge distribution and hence in the location of the chemically reactive centres, the imine partial structure in diazepam and the malonic acid portion of clobazam.