Benzofuran and Pyrrole Derivatives as Cannabinoid Receptor Modulators with In Vivo Efficacy against Ulcerative Colitis

Abstract

Aim: Highlighting the need for effective therapies for the treatment of ulcerative colitis, novel series of potential CB₂ modulators (benzofuran and pyrrole carboxamides) were developed and tested for their functional activities on CB₁/CB₂ receptors. Results: In the benzofuran series, the cannabinoid (CB) receptor selectivity and the functional profile were dependent on the nature of the amide substituent and the position of the methoxy group, meanwhile the pyrrole derivatives, displayed an exclusive selectivity to the CB₂ receptor and a functionality that is controlled by the nature of the pyrrole nitrogen substituent. Conclusion: Remarkably, we succeeded to develop potent and selective pyrrole-based CB₂ receptor agonists, represented by compound 25a, which also demonstrated an exquisite anti-inflammatory effect in a dextran sodium sulfate-induced colitis model in mice.

Keywords: :

• benzofuran
• cannabinoid receptors
• CB modulators
• CB₂ agonist
• DSS-induced colitis
• IBD
• pyrrole

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184

Acknowledgments

The authors gratefully acknowledge the NIMH PDSP (National Institute of Mental Health – Psychoactive Drug Screening Program) team and Prof. Bryan L Roth (NIMH-PDSP director), University of North Carolina, for carrying out the functional assays.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval. All experiments conducted in accordance with the guidelines of the German University in Cairo and The National Research Centre ethics committee's guidelines following the recommendations of The National Institutes of Health Guide for the Care and Use of Laboratory Animals.