| Autor: |
Reem Smoum, Christeene Haj, Shira Hirsch, Alina Nemirovski, Zhannah Yekhtin, Benny Bogoslavsky, Gaganjyot Kaur Bakshi, Mukesh Chourasia, Ruth Gallily, Joseph Tam, Raphael Mechoulam |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Molecules, Vol 27, Iss 4, p 1382 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1420-3049 |
| DOI: |
10.3390/molecules27041382 |
| Popis: |
A series of novel cannabinoid-type derivatives were synthesized by the coupling of (1S,4R)-(+) and (1R,4S)-(−)-fenchones with various resorcinols/phenols. The fenchone-resorcinol derivatives were fluorinated using Selectfluor and demethylated using sodium ethanethiolate in dimethylformamide (DMF). The absolute configurations of four compounds were determined by X-ray single crystal diffraction. The fenchone-resorcinol analogs possessed high affinity and selectivity for the CB2 cannabinoid receptor. One of the analogues synthesized, 2-(2′,6′-dimethoxy-4′-(2″-methyloctan-2″-yl)phenyl)-1,3,3-trimethylbicyclo[2.2.1]heptan-2-ol (1d), had a high affinity (Ki = 3.51 nM) and selectivity for the human CB2 receptor (hCB2). In the [35S]GTPγS binding assay, our lead compound was found to be a highly potent and efficacious hCB2 receptor agonist (EC50 = 2.59 nM, E(max) = 89.6%). Two of the fenchone derivatives were found to possess anti-inflammatory and analgesic properties. Molecular-modeling studies elucidated the binding interactions of 1d within the CB2 binding site. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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