8-Chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines with substituents at C-4

Abstract

A series of 8-chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines with substituents at C-4 was prepared and evaluated for antianxiety potential. It was found that substitution at this position generally decreased the activity in this series.

Synthesis of 1,3,3a,5‐tetraaryl‐3a,4,5,6‐tetrahydro‐3H‐1,2,4‐triazolo[4,3‐a] [1,5]benzodiazepines

“…triazolam, estazolam, and flumazenil were found to be effective in the treatment of some CNS disturbances [1]. Alprazolam and triazolam were shown to have clinically useful anxiolytic and hypnotic activity [2][3][4]. Several triazolobenzodiazepines have been evaluated as antagonists of platelet activating factor [5].…”

“…Hence, a number of synthetic methods have been developed in recent years [6,7], providing interesting and useful routes to annulated 1,4-benzodiazepines [8]. Up to now, much attention has been paid to the synthesis of 1,2,4-triazolo [1,4]benzodiazepines by various methods [9][10][11][12]. However, only a few of the 1,2,4-triazole- fused 1,5-benzodiazepine derivatives have been reported [13][14][15][16].…”

“…Among tricyclic benzodiazepine derivatives, triazolobenzodiazepines are one of the most important families due to their pharmaceutical interest [1][2][3][4][5]. Several triazolobenzodiazepines, e.g.…”

Assay of Adinazolam in Plasma by Liquid Chromatography

“…More recently, adinazolam mesylate, the methanesulfonate salt of 8-chloro-1 -[ (dimethylamino)methyl] -6-phenyl-4H-s-triazolo[4,3-a] [ 1,4]benzodiazepine (I), was shown to have both antidepressant and antianxiety properties (6)(7)(8).…”

“…For this purpose, a liquid chromatographic method was developed for the separation and quantitative determination of adinazolam in human plasma samples. 8-Chloro-1 -[ (methylamino)-methyl]-6-phenyl-4H-s-triazolo[4,3-a] [ 1,4] benzodiazepine (11) (8), an N-demethylated metabolite of adinazolam, found in abundant amounts in the plasma samples, were simultaneously analyzed. [ 1,4]benzodia7,cpine (111) (6) were used as received'.…”