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

Synthetic bioactive olivetol-related amides: The influence of the phenolic group in cannabinoid receptor activity.
Bioorg Med Chem. 2020 Apr 20;:115513
Authors: Brizzi A, Aiello F, Boccella S, Cascio MG, De Petrocellis L, Frosini M, Gado F, Ligresti A, Luongo L, Marini P, Mugnaini C, Pessina F, Corelli F, Maione S, Manera C, Pertwee RG, Di Marzo V
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.
PMID: 32340793 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry - April 19, 2020 Category: Chemistry Authors: Brizzi A, Aiello F, Boccella S, Cascio MG, De Petrocellis L, Frosini M, Gado F, Ligresti A, Luongo L, Marini P, Mugnaini C, Pessina F, Corelli F, Maione S, Manera C, Pertwee RG, Di Marzo V Tags: Bioorg Med Chem Source Type: research