Discovery of DS34942424: An orally potent analgesic without mu opioid receptor agonist activity

Bioorg Med Chem. 2020 Nov 1;28(21):115714. doi: 10.1016/j.bmc.2020.115714. Epub 2020 Aug 18.

Abstract

We identified (5'S)-10'-fluoro-6'-methyl-5',6'-dihydro-3'H-spiro[cyclopropane-1,4'-[2,6]diaza[2,5]methano[2,6]benzodiazonin]-7'(1'H)-one, 22b (DS34942424) with a unique and original bicyclic skeleton. 22b showed an orally potent analgesic in the acetic acid-induced writhing test and formalin test in ddY mice without sedation. Moreover, 22b did not exhibit mu opioid receptor agonist activity.

Keywords: Alkaloid; Analgesic; Conolidine; Non-opioid analgesics.

MeSH terms

  • Administration, Oral
  • Analgesics, Opioid / chemistry*
  • Analgesics, Opioid / metabolism
  • Analgesics, Opioid / pharmacology
  • Analgesics, Opioid / therapeutic use
  • Animals
  • Behavior, Animal / drug effects
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Drug Stability
  • Male
  • Mice
  • Microsomes, Liver / metabolism
  • Pain / chemically induced
  • Pain / drug therapy
  • Pain / pathology
  • Receptors, Opioid, mu / agonists*
  • Receptors, Opioid, mu / metabolism
  • Spiro Compounds / chemistry*
  • Spiro Compounds / metabolism
  • Spiro Compounds / pharmacology
  • Spiro Compounds / therapeutic use
  • Structure-Activity Relationship

Substances

  • Analgesics, Opioid
  • Receptors, Opioid, mu
  • Spiro Compounds