N-Cubylmethyl substituted morphinoids as novel narcotic antagonists

Abstract 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.