Design and synthesis of novel opioid ligands with an azabicyclo[2.2.2]octane skeleton and their pharmacologies

Bioorg Med Chem Lett. 2012 Apr 15;22(8):2689-92. doi: 10.1016/j.bmcl.2012.03.001. Epub 2012 Mar 8.

Abstract

A novel opioid ligand possessing a stable and cyclic imine 16 and its derivatives with an azabicyclo[2.2.2]octane skeleton were synthesized. The imine 16 showed higher affinity for the μ receptor than compound 21 with an oxabicyclo[2.2.2]octane skeleton. Azabicyclo[2.2.2]octane derivative 18d with a cyclopropylmethyl group on the 8-nitrogen showed the highest affinity for the μ receptor among the synthesized derivatives.

MeSH terms

  • Analgesics, Opioid / chemical synthesis
  • Analgesics, Opioid / chemistry
  • Analgesics, Opioid / pharmacology
  • Aza Compounds* / chemical synthesis
  • Aza Compounds* / chemistry
  • Aza Compounds* / pharmacology
  • Bridged Bicyclo Compounds* / chemical synthesis
  • Bridged Bicyclo Compounds* / chemistry
  • Bridged Bicyclo Compounds* / pharmacology
  • Drug Design*
  • Ligands*
  • Molecular Structure
  • Morphinans / chemistry
  • Morphinans / pharmacology
  • Octanes* / chemical synthesis
  • Octanes* / chemistry
  • Octanes* / pharmacology
  • Protein Binding / drug effects
  • Receptors, Opioid / metabolism
  • Receptors, Opioid, mu / metabolism
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology
  • Structure-Activity Relationship

Substances

  • Analgesics, Opioid
  • Aza Compounds
  • Bridged Bicyclo Compounds
  • Ligands
  • Morphinans
  • Octanes
  • Receptors, Opioid
  • Receptors, Opioid, mu
  • Spiro Compounds
  • TRK 820
  • octane