Synthetic bioactive olivetol-related amides: The influence of the phenolic group in cannabinoid receptor activity

Antonella Brizzi*, Francesca Aiello, Serena Boccella, Maria Grazia Cascio, Luciano De Petrocellis, Maria Frosini, Francesca Gado, Alessia Ligresti, Livio Luongo, Pietro Marini, Claudia Mugnaini, Federica Pessina, Federico Corelli, Sabatino Maione, Clementina Manera, Roger G. Pertwee, Vincenzo Di Marzo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Focusing on the importance of the free phenolic hydroxyl moiety, a family of 23 alkylresorcinol-based compounds were developed and evaluated for their cannabinoid receptor binding properties. The non-symmetrical hexylresorcinol derivative 29 turned out to be a CB2-selective competitive antagonist/inverse agonist endowed with good potency. Both the olivetol- and 5-(2-methyloctan-2-yl)resorcinol-based derivatives 23 and 24 exhibited a significant antinociceptive activity. Interestingly, compound 24 proved to be able to activate both cannabinoid and TRPV1 receptors. Even if cannabinoid receptor subtype selectivity remained a goal only partially achieved, results confirm the validity of the alkylresorcinol nucleus as skeleton for the identification of potent cannabinoid receptor modulators.

Original languageEnglish
Article number115513
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume28
Issue number11
Early online date20 Apr 2020
DOIs
Publication statusPublished - 1 Jun 2020

Keywords

  • Alkylresorcinols
  • Antinociceptive effect
  • Cannabinoid ligands
  • Dual ligand
  • Endocannabinoids
  • Transient receptor potential vanilloid type-1 channel

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