N-Cubylmethyl substituted morphinoids as novel narcotic antagonists

Article abstract of DOI:10.1016/0968-0896(95)00165-4

N-Cubylmethylnormorphine (1) and N-cubylmethylnoroxymorphone (2) have been synthesized and found to be more potent ligands at the μ and κ opioid receptors than morphine and oxymorphone respectively. In the guinea-pig ileum preparation, compounds 1 and 2 were characterized as opioid μ antagonists (Ke=68 and 16 nM, respectively). Compound 2 also showed effective κ-antagonism (Ke=22 nM). The narcotic antagonism activity of 1 has been confirmed by in vivo assays.