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.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis*; D000927:Anticonvulsants / Q000138:chemical synthesis; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000494:pharmacology; D003975:Diazepam / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006900:Hydroxylation; D008297:Male; D008722:Methods; D051379:Mice; D010084:Oxidation-Reduction; D014229:Triazolam / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D014230:Triazoles; D001569:Benzodiazepines; D014229:Triazolam; D003975:Diazepam