Synthesis of Novel Triplets with a 1,3,5‐Trioxazatriquinane Skeleton and Their Pharmacologies for Opioid Receptors

Abstract

We designed and synthesized novel triplet molecules with 1,3,5‐trioxazatriquinane skeletons. One class comprises double‐capped triplets with a morphinan skeleton; the other class comprises simple phenol derivatives with phenethylamine moieties. One compound with m‐phenolic hydroxyl group, called SYK‐146, is a highly selective, potent agonist for the κ receptor, with activity nearly equivalent to that of U‐50488H. The o‐phenolic isomer of SYK‐146, called SYK‐524, showed potent but non‐selective agonistic activity for the opioid receptors. We also added several simple phenol derivatives to a library of compounds that target opioid receptors, and they showed high hit rates for the receptor. This library might also be expected to show high hit rates for other receptors.