A novel rearrangement reaction of morphinan to arylmorphan skeletons and the pharmacologies of arylmorphan derivatives

A novel rearrangement reaction of the morphinan skeleton by using zinc iodide was developed. The substrate-specific rearrangement afforded two types of novel 5-arylmorphan derivatives, i.e., compounds produced by either a 1,5-shift of the nitrogen bridge or a 1,3-shift of the nitrogen bridge in a starting morphinan derivative. The 5-arylmorphan derivatives showed selective K opioid receptor activities even though many 5-arylmorphan compounds reported previously have shown selective ji opioid receptor activities. In addition, other related 5-arylmorphan derivatives showed potent dual antagonistic activities toward orexin 1 and 2 receptors.