Synthesis and biological activity of 8beta-substituted hydrocodone indole and hydromorphone indole derivatives

Bioorg Med Chem Lett. 2002 Jan 21;12(2):165-8. doi: 10.1016/s0960-894x(01)00689-8.

Abstract

The 8beta-unsubstituted and substituted analogues of hydrocodone indole and hydromorphone indole were synthesized and their binding affinities to opioid receptors were determined. Introduction of an 8beta-methyl group into the indolomorphinan nucleus increased affinity at all opioid receptors. 6,7-Dehydro-4,5alpha-epoxy-8beta-methyl-6,7,2',3'-indolomorphinan (9) was found to be a delta antagonist with subnanomolar affinity (0.7 nM) for the delta-opioid receptor, and to have good delta-selectivity (mu/delta=322).

Publication types

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

MeSH terms

  • Hydrocodone / chemistry*
  • Hydromorphone / chemistry*
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Receptors, Opioid / drug effects
  • Structure-Activity Relationship

Substances

  • Indoles
  • Receptors, Opioid
  • Hydrocodone
  • Hydromorphone