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7 Medicinal chemistryBenzodiazepines (BDZ)
Members of this group of heterocyclic compounds are interesting in that structurally
they have both six- and seven-membered rings, and some also have a five-membered
ring. Their C-containing ring structures make benzodiazepines poorly water-soluble
and diazepam requires a special lipid emulsion preparation (diazemuls) to be used
intravenously. However, by altering the hydrocarbon groups and pH, an alternative
tautomeric form without a closed seven-membered ring can be formed. Thus mida-
zolam is presented in the ampoule as a water-soluble drug, but when it reaches the
plasma it returns to the more lipid-soluble ring form (Figure17.1). There are three
groups of BDZs: 1,4 –benzodiazepines (diazepam, temazepam, lorazepam), hetero-
cyclic benzodiazepines (midazolam) and 1,5-benzodiazepines (clobazam). Some of
the 1,4-BDZs are metabolically related; diazepam is metabolized to oxazepam and
temazepam.