STUDIES ON ANNULATED 1,4-BENZOTHIAZINES AND 1,5-BENZOTHIAZEPINES .9. IMIDAZO[2,1-D][1,5]BENZOTHIAZEPINES - SYNTHESIS AND IN-VITRO BENZODIAZEPINE RECEPTOR AFFINITY

The synthesis of three series of 1- and 2-substituted imidazo[2,1-d][1,5]benzothiazepines is accomplished starting from 1,5-benzothiazepin-4-ones. All the synthesized compounds were evaluated for their affinity for the benzodiazepine receptor, testing their ability to displace [H-3]Flunitrazepam from bovine brain membrane protein. A few of the tested compounds showed good affinity, in particular compound 9a (K-i = 43.00 nM). The GABA-ratio of the active compounds suggests an antagonist or partial agonist activity. The data obtained allow us to draw some comments on the structure-activity relationships.