1,4-Benzodiazepines and 1,5-benzodiazocines XI. Synthesis and biological activity

Abstract The synthesis of a new class of anellated 1,4-benzodiazepines with anti-psychotic activity is exemplified by preparation of 10-fluoro-3-methyl-7-(2-thienyl)-1,2,3,4,4a,5-hexahydropyrazino[1,2- a ][1,4]benzodiazepine (timelotem). The influence of variations of the fluoro-substitution pattern and variations of the fused ring system on the biological activity of the structural analogues is evaluated. In vivo , the potency of the compounds to antagonize apomorphine induced climbing (taken as being indicative of anti-psychotic activity) and their ability to inhibit pentetrazole-induced seizures (indicating similarities to benzodiazepine minor tranquilizers) are determined. In vitro the affinities of the compounds to both dopamine-D 2 and benzodiazepine receptors are measured.