Mixed kappa agonists and mu agonists/antagonists as potential pharmacotherapeutics for cocaine abuse: Synthesis and opioid receptor binding affinity of N-substituted derivatives of morphinan

A series of new N-substituted derivatives of morphinan was synthesized and their binding affinity for the three opioid receptors (mu, delta, and kappa ) was determined. A paradoxical effect of N-propargyl (MCL-117) and N-(3-io doprop-(2E)-enyl) (MCL-118) substituents on the binding affinities for the mu and kappa opioid receptors was observed. All of these novel derivatives showed a preference for the mu and kappa versus delta binding. (C) 2001 Els evier Science Ltd. All rights reserved.