Novel multiple opioid ligands based on 4-aminobenzazepinone (Aba), azepinoindole (Aia) and tetrahydroisoquinoline (Tic) scaffolds

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1610-3. doi: 10.1016/j.bmcl.2010.01.055. Epub 2010 Jan 20.

Abstract

The dimerization and trimerization of the Dmt-Tic, Dmt-Aia and Dmt-Aba pharmacophores provided multiple ligands which were evaluated in vitro for opioid receptor binding and functional activity. Whereas the Tic- and Aba multimers proved to be dual and balanced delta/mu antagonists, as determined by the functional [S(35)]GTPgammaS binding assay, the dimerization of potent Aia-based 'parent' ligands unexpectedly resulted in substantial less efficient receptor binding and non-active dimeric compounds.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzazepines / chemical synthesis
  • Benzazepines / chemistry*
  • Benzazepines / pharmacology
  • Dimerization
  • Drug Design
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacology
  • Ligands*
  • Protein Binding
  • Rats
  • Receptors, Opioid, delta / antagonists & inhibitors*
  • Receptors, Opioid, delta / metabolism
  • Receptors, Opioid, mu / antagonists & inhibitors*
  • Receptors, Opioid, mu / metabolism
  • Tetrahydroisoquinolines / chemical synthesis
  • Tetrahydroisoquinolines / chemistry*
  • Tetrahydroisoquinolines / pharmacology

Substances

  • Benzazepines
  • Indoles
  • Ligands
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Tetrahydroisoquinolines