Synthesis and sigma binding properties of 1'- and 3'-halo- and 1',3'-dihalo-N-normetazocine analogues

J Med Chem. 1995 Jul 21;38(15):2986-9. doi: 10.1021/jm00015a023.

Abstract

The synthesis and sigma 1 and sigma 2 binding properties of several 1'- and 3'-halo- and 1',3'-dihalo-substituted analogues of (+)-N-benzyl- and (+)- and (-)-N-dimethylallyl-N-normetazocine are presented. Structure-activity relationship analyses of the binding data showed that halogen substitution at the 1'-position of these N-substituted N-normetazocine analogues had little effect on sigma 1 binding affinity, whereas 3'-halo substitution as well as 1',3'-dihalo substitution resulted in a reduction of affinity. sigma 2 affinity was increased by the presence of a 3'-bromo substituent in this series of (+)-N-substituted N-normetazocines.

Publication types

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

MeSH terms

  • Animals
  • Cyclazocine / analogs & derivatives*
  • Cyclazocine / chemical synthesis
  • Cyclazocine / metabolism
  • Cyclazocine / pharmacology
  • Guinea Pigs
  • Hydrocarbons, Halogenated / chemical synthesis*
  • Hydrocarbons, Halogenated / metabolism
  • Hydrocarbons, Halogenated / pharmacology*
  • Narcotics / chemical synthesis*
  • Narcotics / metabolism*
  • Narcotics / pharmacology
  • Pentazocine / analogs & derivatives
  • Rats
  • Receptors, sigma / drug effects
  • Receptors, sigma / metabolism*
  • Structure-Activity Relationship

Substances

  • Hydrocarbons, Halogenated
  • Narcotics
  • Receptors, sigma
  • normetazocine
  • Cyclazocine
  • Pentazocine