Synthesis of New N,N'-Diarylureas and Their Theoretical Study as Cannabinoid-1 Receptor Inhibitors
- Chempluschem. 2025 Jun 13:e2500270. doi: 10.1002/cplu.202500270.
- 1. Laboratory of Organic Chemistry, Department of Chemistry, University of Ioannina, Ioannina, 45110, Greece.
- 2. Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, Athens, 15784, Greece.
- 3. Laboratory of Physical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, Athens, 15784, Greece.
- 4. Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation, 48 Vassileos Constantinou Ave., Athens, 11635, Greece.
A series of new N,N'-diarylureas is reported as potential cannabinoid-1 (CB-1) receptor inhibitors. The synthesis of the new N,N'-diarylureas is achieved from the reaction of two substituted anilines with the aid of triphosgene. One aniline carries a pyrazol-1-yl or 1H-1,2,3-triazolyl or 2H-1,2,3-triazolyl propan-2-one group at position-3, while the Other aniline is substituted by fluoro, bromo, methoxy, cyano, morpholino, or 4-methyl-2-nitro groups. All new compounds are investigated through density functional theory calculations, molecular docking, and molecular dynamics simulations, showing a strong ability to bind to the orthosteric pocket of the CB-1 receptor and to the allosteric position when CB1 is in complex with agonist AM841. The binding is comparable to that of the well-known CB-1 inhibitor PSNBAM-1. Especially, 1-{3-[2-(1H-pyrazol-1-yl)acetyl]phenyl}-3-(4-methyl-3-nitrophenyl)urea presents better theoretical results than PSNBAM-1.
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Cat. No.Product NameDescriptionTargetResearch Area
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target: Cannabinoid Receptor