Pharmacology of some metabolites of triazolam, alprazolam, and diazepam prepared by a simple, one-step oxidation of benzodiazepines

A simple, one-step chemical oxidation of triazolam (7) to its 4-hydroxy analogue, 7a, has been developed and applied to other triazolo- and imidazobenzodiazepines. The reaction may be used to convert diazepam to temazepam. 4-Hydroxytriazolo[4,3-a][1,4]benzodiazepines have low central nervous system sedative and anticonvulsant activity in sharp contrast to metabolites of diazepam which remain active. While 10, an alpha-hydroxy metabolite of triazolam, retains much of the activity of 7, 10a, and alpha,4-dihydroxy metabolite of triazolam, is 250 times less potent than 7 on the nicotine-antagonism assay and over 300 times less potent on the traction assay.