N-substituted octahydro-4a-(3-hydroxyphenyl)-10a-methyl-benzo[g]isoquinolines are opioid receptor pure antagonists

Bioorg Med Chem Lett. 1998 Nov 17;8(22):3149-52. doi: 10.1016/s0960-894x(98)00576-9.

Abstract

N-Methyl- and N-phenylethyl-(+/-)-1,2,3,4,4a,5,10,10a- octahydro-4a-(3-hydroxyphenyl)-10a-methyl-benzo[g]isoquinolines (4 and 5, respectively) were found to be pure opioid antagonists. These compounds were shown to share many of the characteristics identified with the N-methyl- and N-phenylethyl trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (1 and 2, respectively) including N-substituent mediated potency and a lack of N-substituent mediated antagonism. These data suggest that compounds 4 and 5 and the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines (1 and 2) may interact with opioid receptors similarly.

Publication types

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

MeSH terms

  • Animals
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Guinea Pigs
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / pharmacology
  • Narcotic Antagonists* / chemical synthesis*
  • Narcotic Antagonists* / pharmacology
  • Piperidines / pharmacology
  • Structure-Activity Relationship

Substances

  • Isoquinolines
  • Narcotic Antagonists
  • Piperidines
  • Guanosine 5'-O-(3-Thiotriphosphate)