Abstract A series of novel benzoxepin-derived compounds were synthesized and evaluated for their sedative–hypnotic effect using Phenobarbital-induced sleep test in mice. Compound 6 in which the Phenobarbital moiety was incorporated into the benzoxepin nucleus was the most active one. Molecular modeling, including fitting to a 3D-pharmacophore model using Discovery Studio 2.1 programs into optimized benzodiazepine receptor (hypothesis) ...