A novel [5.2.1]bicyclic amine is a potent analgesic without µ opioid activity

Bioorg Med Chem Lett. 2021 Mar 15:36:127790. doi: 10.1016/j.bmcl.2021.127790. Epub 2021 Jan 14.

Abstract

We identified (5R)-6-methyl-5-phenyl-1,3,4,5,6,7-hexahydro-2,5-methano-2,6-benzodiazonine (DS21980956: 4-(R)) as a novel [5.2.1]bicyclic basic compound. The scaffold was inspired by fentanyl or pethidine, which possess potent analgesic activities. DS21980956 had potent analgesic activity in the mouse acetic acid writhing test or tail flick test without agonistic activity at the µ opioid receptor (MOR). The mechanism of analgesic action of DS21980956 was considered to differ from a biased ligand, for example, TRV-130 (3, oliceridine).

Keywords: Analgesic; Bicyclic amine; Naloxone; Non-opioid; Tail flick test.

MeSH terms

  • Acetic Acid
  • Amines / chemistry
  • Amines / therapeutic use*
  • Analgesics / chemistry
  • Analgesics / therapeutic use*
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use*
  • Dose-Response Relationship, Drug
  • Mice
  • Mice, Inbred Strains
  • Molecular Structure
  • Pain / chemically induced
  • Pain / drug therapy*
  • Pain Measurement
  • Structure-Activity Relationship

Substances

  • Amines
  • Analgesics
  • Bridged Bicyclo Compounds, Heterocyclic
  • Acetic Acid