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

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

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

Unite de Chimie Pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, Faculte
de Medecine, Universite catholique de Louvain, Avenue E. Mounier 73, UCL-CMFA
7340, B-1200 Bruxelles, Belgium.

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.

PMID: 15801840 [PubMed - in process]