Synthesis and pharmacological evaluation of new biphenylic derivatives as CB2 receptor ligands

Bertini, Simone; Chicca, Andrea; Arena, Chiara; Chicca, Stefano; Saccomanni, Giuseppe; Gertsch, Jürg; Manera, Clementina; Macchia, Marco (2016). Synthesis and pharmacological evaluation of new biphenylic derivatives as CB2 receptor ligands. European journal of medicinal chemistry, 116, pp. 252-266. Elsevier Masson SAS 10.1016/j.ejmech.2016.03.072

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Targeting type-2 cannabinoid receptor (CB2) is considered a feasible strategy to develop new drugs for the treatment of diseases like neuropathic pain, chronic inflammation, neurodegenerative disorders and cancer. Such drugs are devoid of the undesired central side effects that are typically mediated by the CB1 receptor. In this work we synthesized 18 biphenylic carboxamides as new CB2-selective ligands and evaluated their pharmacological profiles. The functional activity of these compounds is strongly influenced by the nature of the substituent at position 4' and 5 of the biphenyl scaffold. Position 5 seems to be responsible for the agonist or inverse agonist behaviour independently of the substituent in position 4', with the exception of the methoxyl group which transforms both full agonists and inverse agonists into neutral antagonists. This study provides a novel complete toolbox of CB2 functional modulators that derive from the same chemical scaffold. Such probes may be useful to investigate the biological role of CB2 receptors in cellular assays.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Faculty Institutions > NCCR TransCure
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Chicca, Andrea, Arena, Chiara, Gertsch, Jürg


500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health




Elsevier Masson SAS




Valentina Rossetti

Date Deposited:

15 Sep 2016 11:25

Last Modified:

05 Dec 2022 14:58

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Biphenyl-carboxamides; CB(2); CB(2) agonist; CB(2) antagonist; CB(2) inverse agonist; Cannabinoid receptor; Endocannabinoid system; Methylhonokiol




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