14-amino, 14-alkylamino, and 14-acylamino analogs of oxymorphindole. Differential effects on opioid receptor binding and functional profiles

J Med Chem. 2003 Apr 10;46(8):1563-6. doi: 10.1021/jm021073r.

Abstract

The 14-amino analogue of oxymorphindole (OMI) was synthesized and found to possess delta-opioid binding affinity and selectivity similar to OMI. Substitution of the amino group with alkyl, arylalkyl, and acyl groups had relatively little effect on delta-affinity but delta-selectivity was reduced. In functional assays the 14-phenylacetylamino derivative 6d was a selective delta-agonist whereas the phenethylamino analogue 5d was a mu-agonist and low efficacy delta partial agonist that warrants further investigation as an analgesic with low tolerance and dependence.

Publication types

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

MeSH terms

  • Analgesics, Opioid / chemical synthesis*
  • Analgesics, Opioid / chemistry
  • Analgesics, Opioid / pharmacology
  • Animals
  • Binding, Competitive
  • CHO Cells
  • Cricetinae
  • Morpholines / chemical synthesis*
  • Morpholines / chemistry
  • Morpholines / pharmacology
  • Radioligand Assay
  • Receptors, Opioid, delta / agonists*
  • Receptors, Opioid, delta / metabolism
  • Receptors, Opioid, mu / agonists*
  • Receptors, Opioid, mu / metabolism
  • Structure-Activity Relationship

Substances

  • Analgesics, Opioid
  • Morpholines
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • oxymorphindole