Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1374260 | Bioorganic & Medicinal Chemistry Letters | 2010 | 6 Pages |
Abstract
The cannabinoid CB1/CB2 receptor subtype selectivity in the 1,2-diarylimidazole-4-carboxamide series was boosted by fine-tuning its 5-substitution pattern. The presence of the 5-methylsulfonyl group in 11 led to a greater than ∼840-fold CB1/CB2 subtype selectivity. The compounds 10, 18 and 19 were found more active than rimonabant (1) in a CB1-mediated rodent hypotension model after oral administration. Our findings suggest a limited brain exposure of the P-glycoprotein substrates 11, 12 and 21.
Graphical abstractCompound 11 showed >∼840-fold CB1/CB2 subtype selectivity whereas 6 was only 31-fold selective.Figure optionsDownload full-size imageDownload as PowerPoint slide
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Jos H.M. Lange, Martina A.W. van der Neut, Alice J.M. Borst, Mahmut Yildirim, Herman H. van Stuivenberg, Bernard J. van Vliet, Chris G. Kruse,