Substituted 5,5′-diphenyl-2-thioxoimidazolidin-4-one as CB 1 cannabinoid receptor ligands: Synthesis and pharmacological evaluation

Giulio G. Muccioli, Diana Martin, Gerhard K E Scriba, Wolfgang Poppitz, Jacques H. Poupaert, Johan Wouters, Didier M. Lambert

Research output: Contribution to journalArticle

Abstract

A set of 30 substituted 5,5′-diphenyl-2-thioxoimidazolidin-4-one (thiohydantoins) derivatives was synthesized, and their affinity for the human CB1 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 [35S]-GTPγS 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.

Original languageEnglish
Pages (from-to)2509-2517
Number of pages9
JournalJournal of Medicinal Chemistry
Volume48
Issue number7
DOIs
Publication statusPublished - 7 Apr 2005

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  • Datasets

    CCDC 619188: Experimental Crystal Structure Determination

    Lambert, D. M. (Contributor), Martin, D. (Contributor), Muccioli, G. (Contributor), Poppitz, W. (Contributor), Poupaert, J. H. (Contributor), Scriba, G. K. E. (Contributor) & WOUTERS, J. (Contributor), Cambridge Crystallographic Data Centre, 1 Jan 2006

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