5-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-phenyl-2,3,6,7-tetrahydro1,4-thiazepines as compounds with high affinity at the benzodiazepine binding site on GABAA receptors

A series of thiazepines has been studied as new ligands for the benzodiazepine binding site of the GABAA receptor. Compounds with high affinity and weak selectivity regarding α1 β 2, γ2, α 2β3, gamma;2, α3 β3 γ2 and α5 β3 γ2 subtypes were found. The pharmacophore is discussed based on experimental and theoretical results. The thiazepine sulfur atom was found to be able to act as hydrogen bond acceptor.