The demonstration of the essential role of fatty acid amide hydrolase (FAAH) in hydrolyzing endogenous bioactive fatty acid derivatives has launched the quest for the discovery of inhibitors for this enzyme. Along this line, a set of 58 imidazolidine-2,4-dione and 2-thioxoimidazolidin-4-one derivatives was evaluated as FAAH inhibitors. Among these compounds, 3-substituted 5,5′-diphenylimidazolidine-2,4-dione and 3-substituted 5,5′-diphenyl-2-thioxoimidazolidin-4-one derivatives were previously described as CB 1 cannabinoid receptor ligands. In the present study, we synthesized several derivatives exhibiting interesting FAAH inhibitory activity and devoid of affinity for the CB 1 and CB 2 cannabinoid receptors. For instance, 3-heptyl-5,5′-diphenylimidazolidine-2,4-dione (14) and 5,5′-diphenyl-3-tetradecyl-2-thioxo-imidazolidin-4-one (46) showed pI 50 values of 5.12 and 5.94, respectively. In conclusion, it appears that even though several 3-substituted 5,5′-diphenyl-2-thioxoimidazolidin-4-one and 3-substituted 5,5′-diphenylimidazolidine-2,4-dione derivatives have been previously shown to behave as CB 1 cannabinoid receptor ligands, appropriate substitutions of these templates can result in FAAH inhibitors devoid of affinity for the cannabinoid receptors.

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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.

Obesity and metabolic syndrome, along with drug dependence (nicotine, alcohol, opiates), are two of the major therapeutic applications for CB(1) cannabinoid receptor antagonists and inverse agonists. In the present study, we report the synthesis and structure-affinity relationships of 1,5-diphenylimidazolidine-2,4-dione and 1,3,5-triphenylimidazolidine-2,4-dione derivatives. These new 1,3,5-triphenylimidazolidine-2,4-dione derivatives and their thio isosteres were obtained by an original pathway and exhibited interesting affinity and selectivity for the human CB(1) cannabinoid receptor. A [(35)S]-GTPgammaS binding assay revealed the inverse agonist properties of the compounds at the CB(1) cannabinoid receptor. Furthermore, molecular modeling studies were conducted in order to delineate the binding mode of this series of derivatives into the CB(1) cannabinoid receptor. 1,3-Bis(4-bromophenyl)-5-phenylimidazolidine-2,4-dione (25) and 1,3-bis(4-chlorophenyl)-5-phenylimidazolidine-2,4-dione (23) are the imidazolidine-2,4-dione derivatives possessing the highest affinity for the human CB(1) cannabinoid receptor reported to date.

Carbon soot has been prepared by laser-induced pyrolysis of a mixture of ethylene (C 2 H 4 ) and benzene (C 6 H 6 ) vapor. The soluble part of the carbonaceous powder has been separated from its insoluble counterpart by soxhlet extraction in toluene. Several techniques were applied to obtain information on the composition of the extract. These included UV/visible and IR spectroscopy in solid and liquid phase, gas chromatography combined with mass spectrometry, gas-phase laser spectroscopy in a supersonic jet, and matrix spectroscopy in helium droplets, the latter being also combined with mass spectrometry. The analysis revealed that the carbonaceous powder contained various polycyclic aromatic hydrocarbons (PAHs). The highest concentration was found for the three-membered catacondensed PAHs, phenanthrene and anthracene. The results are discussed in view of the possible role of these molecules as interstellar dust components.