Substituted 5,5'-diphenyl-2-thioxoimidazolidin-4-one as CB1 cannabinoid receptor ligands: synthesis and pharmacological evaluation.

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Muccioli GG, Martin D, Scriba GK, Poppitz W, Poupaert JH, Wouters J, Lambert DM

Substituted 5,5'-diphenyl-2-thioxoimidazolidin-4-one as CB1 cannabinoid receptor ligands: synthesis and pharmacological evaluation.

J Med Chem. 2005 Apr 7;48(7):2509-17.

PubMed ID

15801840 [ View in PubMed

]

Abstract

A set of 30 substituted 5,5'-diphenyl-2-thioxoimidazolidin-4-one (thiohydantoins) derivatives was synthesized, and their affinity for the human CB(1) cannabinoid receptor has been evaluated. These compounds are derived from the previously described cannabinoid ligands 5,5'-diphenylimidazolidine-2,4-dione (hydantoins). The replacement of the oxygen by a sulfur leads to an increase of the affinity while the function-i.e., inverse agonism-determined by [(35)S]GTPgammaS experiments remains unaffected. Finally, to evaluate the molecular parameters that could influence the affinity of the thiohydantoins, molecular electrostatic potential as well as lipophilicity calculations were undertaken on representative thiohydantoins and hydantoins derivatives. In conclusion, 5,5'-bis-(4-iodophenyl)-3-butyl-2-thioxoimidazolidin-4-one (31) and 3-allyl-5,5'-bis(4-bromophenyl)-2-thioxoimidazolidin-4-one (32) possess the highest affinity for the CB(1) cannabinoid receptor described to date for the hydantoin and thiohydantoins series when compared in a same bioassay.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Rimonabant	Cannabinoid receptor 1	Ki (nM)	5.4	N/A	N/A	Details