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

Bioorg Med Chem Lett. 2001 Oct 22;11(20):2735-40. doi: 10.1016/s0960-894x(01)00543-1.


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-iodoprop-(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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cocaine-Related Disorders / drug therapy
  • Drug Combinations
  • Humans
  • Morphinans / chemical synthesis
  • Morphinans / chemistry
  • Morphinans / pharmacology*
  • Morphinans / therapeutic use
  • Narcotic Antagonists / pharmacology
  • Narcotic Antagonists / therapeutic use
  • Receptors, Opioid, kappa / agonists*
  • Receptors, Opioid, mu / agonists*
  • Receptors, Opioid, mu / antagonists & inhibitors


  • Drug Combinations
  • Morphinans
  • N-(3-iodoprop-(2)-enyl)
  • N-propargyl
  • Narcotic Antagonists
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu