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Updated: Jun 14, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Probing the cannabinoid CB1/CB2 receptor subtype selectivity limits of 1,2-diarylimidazole-4-carboxamides by
Jos H M Lange1, Martina A W van der Neut, Alice J M Borst
1Solvay Pharmaceuticals, Research Laboratories, C. J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands. jos.lange@solvay.com
Abstract:
The cannabinoid CB(1)/CB(2) 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 approximately 840-fold CB(1)/CB(2) subtype selectivity. The compounds 10, 18 and 19 were found more active than rimonabant (1) in a CB(1)-mediated rodent hypotension model after oral administration. Our findings suggest a limited brain exposure of the P-glycoprotein substrates 11, 12 and 21.
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