As a continuation of our search for new ligands acting on benzodiazepine receptors among the fused 2-thiohydantoin derivatives, a series of 5-substituted imidazo[2,1-b]thiazepines was synthesized and investigated in radioligand binding studies at the benzodiazepine binding site of GABA(A) receptors in rat brain cortical membranes. Among ortho-substituted 5-arylidene-imidazo[2,1-b]thiazepines compounds could be identified which exhibit affinity for the benzodiazepine binding site at low micromolar concentrations. X-ray structure analyses for two compounds (6ae and 6ag) have been performed. In order to analyze the structure-activity relationships, 3D models of all compounds have been completed (using X-ray data). Physicochemical properties calculated (log P and log D) as well as experimental thin layer chromatography data were examined.