The discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine cannabinoid type 2 receptor agonist.

Michael Moir, Samuel Lane, Andrew P. Montgomery, David Hibbs, Mark Connor, Michael Kassiou

Research output: Contribution to journalArticlepeer-review

Abstract

The development of selective CB2 receptor agonists is a promising therapeutic approach for the treatment of inflammatory diseases, without CB1 receptor mediated psychoactive side effects. Preliminary structure-activity relationship studies on pyrazoylidene benzamide agonists revealed the -ylidene benzamide moiety was crucial for functional activity at the CB2 receptor. A small library of compounds with varying linkage moieties between the pyrazole and substituted phenyl group has culminated in the discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine agonist 19 (CB2R EC50 = 19 nM, CB1R EC50 > 10 μM). Docking studies have revealed key structural features of the linkage group that are important for potent functional activity.
Original languageEnglish
Article number113087
Pages (from-to)1-28
Number of pages28
JournalEuropean Journal of Medicinal Chemistry
Volume210
DOIs
Publication statusPublished - 15 Jan 2021

Keywords

  • CB(2)R selective;
  • Cannabinoid
  • Docking
  • Pyrazolotriazine
  • Structure-activity relationship study
  • Synthesis
  • CB R selective

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