1-(Aminoalkyl)-6-aryl-4H-s-triazolo[4,3-a][1,4]benzodiazepines with antianxiety and antidepressant activity

Abstract

A series of 1-(aminoalkyl)-6-aryl-4H-s-triazolo[4,3-a][1,4]benzodiazepines has been prepared and evaluated for central nervous system activity. We have found that members of this series have activity in pharmacological test systems designed to detect both anxiolytic and antidepressant activity. Each type of activity could be varied independently by appropriate substituent selections.

Mechanism of triazolo-benzodiazepine and benzodiazepine action in anxiety and depression: Behavioral studies with concomitant in vivo CA1 hippocampal norepinephrine and serotonin release detection in the behaving animal

“…An overview of the scientific literature reveals that the TBZDs differ strikingly in pharmacological activity from the BZDs, in that the TBZDs show positive results in some assays used to test antidepressant activity (Hester et al, 1980;Lahti et al, 1983;Sethy et al, 1984). The present results agree with these positive results, e.g., the report of potentiation of NE-induced enhancement of blood pressure (Sethy and Hodges, 1982).…”

“…was made during the broad pharmacological and clinical screening of the TBZD series of compounds (Hester et al, 1971;Hester et al, 1980;Pyke et al, 1983;Hoehn-Saric, 1982). Indeed, the sister compound to adinazolam, alprazolam, differing from adinazolam only by a terminal aminoethyl group, has been commonly used in the clinical management of mild depressive syndromes with anxiety and insomnia (Sheehan, 1980;Chouinard et al, 1982;Shader et al, 1982;Fawcett et al, 1987).…”

Studies on synthesis and evaluation of quantitative structure–activity relationship of 10-methyl-6-oxo-5-arylazo-6,7-dihydro-5H-[1,3]azaphospholo[1,5-d][1,4]benzodiazepin-2-phospha-3-ethoxycarbonyl-1-phosphorus dichlorides

“…[1][2][3][4][5] Interest in the chemistry, synthesis and biology of this pharmacophore continues to be fuelled by their activity against a variety of CNS disorders as well as due to wide biological properties such as antianxiety, anticonvulsant, sedative/hypnotic, muscle relaxing and tranquilizing. [6][7][8] Many drugs incorporating BDZ core nucleus which extensively binds to plasma and tissue proteins have been developed over the past two decades and they became the most commonly prescribed group of psychotherapeutic drugs worldwide. 9,10 After the discovery of benzodiazepine receptors in the CNS and peripheral tissues 11,12 many attempts have also been made to correlate the molecular structure with the biological activity of these compounds.…”

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

“…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.…”