New-generation azaindole-adamantyl-derived synthetic cannabinoids

Mitchell Longworth, Tristan A. Reekie, Karen Blakey, Rochelle Boyd, Mark Connor, Michael Kassiou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
60 Downloads (Pure)

Abstract

Purpose: This work reports the synthesis and pharmacological and analytical data for a new series of recently identified azaindole-adamantyl-derived synthetic cannabinoids (SCs). Methods: Each SC was synthesised using an efficient and divergent synthesis, and assessed by electron ionisation mass spectrometry (EIMS). The cannabimimetic activity of each compound was conducted using a fluorometric imaging plate reader (FLIPR) assay. Results: The described EIMS method and retention time by gas chromatography were able to effectively differentiate each of the analogues regardless of the bicyclic core. For the first time in these SC structures, the bicyclic ring system was shown to have an impact on the cannabimimetic activities in the fluorometric assay of membrane potential. Analogues ranged from moderately potent at both CB1 and CB2 (e.g., AP4AIC EC50 = 160 nM and EC50 = 64 nM, respectively) to not active at either cannabinoid receptor (AP4AICA, AP5AICA, and APIC). Conclusions: Further investigation into receptor selectivity surrounding these bicyclic cores could prove useful for future therapeutic applications.

Original languageEnglish
Pages (from-to)350-365
Number of pages16
JournalForensic Toxicology
Volume37
Issue number2
Early online date28 Feb 2019
DOIs
Publication statusPublished - Jul 2019

Bibliographical note

Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Adamantyl
  • APICA
  • Azaindole
  • CB1 and CB2
  • Gas chromatography–mass spectrometry
  • Synthetic cannabinoid

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