Novel sterically hindered cannabinoid CB1 receptor ligands.

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Urbani P, Cascio MG, Ramunno A, Bisogno T, Saturnino C, Di Marzo V

Novel sterically hindered cannabinoid CB1 receptor ligands.

Bioorg Med Chem. 2008 Aug 1;16(15):7510-5. doi: 10.1016/j.bmc.2008.06.001. Epub 2008 Jun 7.

PubMed ID

18579386 [ View in PubMed

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Abstract

In the present study, 11 novel N-(3,3-diphenyl)propyl-2,2-diphenylacetamide derivatives (4a-d and 9a-g) and six triphenylacetamides (10a-c and 11a-c) were synthesized and tested as ligands of cannabinoid CB(1) and CB(2) receptors. All compounds exhibited affinity for CB(1) and CB(2) receptors. Four compounds (4b, 9a, 9b, and 11a) showed selectivity for CB(1) versus CB(2) receptors, although only the N-(3,3-diphenyl)propyl-2,2-diphenylacetamide (4b) can be considered a potent CB(1) ligand (K(i)=58 nM). It was 140-fold selective over CB(2) receptors (K(i)=7800 nM) and behaved as an inverse agonist by stimulating forskolin-induced cAMP formation in mouse N18TG2 neuroblastoma cells. This compound is the first of a novel class of tetraphenyl CB(1) ligands that, in view of its easy synthesis and high affinity for CB(1) receptors and despite its sterical hindrance, will be useful for the design of new blockers of this therapeutically exploitable receptor type.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Rimonabant	Cannabinoid receptor 1	Ki (nM)	8	N/A	N/A	Details