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Synthesis and activity of 1,3,5-triphenylimidazolidine-2,4-diones and 1,3,5-triphenyl-2-thioxoimidazolidin-4-ones: characterization of new CB1 cannabinoid receptor inverse agonists/antagonists.
J Med Chem. 2006 Feb 09; 49(3):872-82.JM

Abstract

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.

Authors+Show Affiliations

Unité de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, Faculté de Médecine, Université catholique de Louvain, Avenue E. Mounier 73, UCL-CMFA 7340, B-1200 Brussels, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16451053

Citation

Muccioli, Giulio G., et al. "Synthesis and Activity of 1,3,5-triphenylimidazolidine-2,4-diones and 1,3,5-triphenyl-2-thioxoimidazolidin-4-ones: Characterization of New CB1 Cannabinoid Receptor Inverse Agonists/antagonists." Journal of Medicinal Chemistry, vol. 49, no. 3, 2006, pp. 872-82.
Muccioli GG, Wouters J, Charlier C, et al. Synthesis and activity of 1,3,5-triphenylimidazolidine-2,4-diones and 1,3,5-triphenyl-2-thioxoimidazolidin-4-ones: characterization of new CB1 cannabinoid receptor inverse agonists/antagonists. J Med Chem. 2006;49(3):872-82.
Muccioli, G. G., Wouters, J., Charlier, C., Scriba, G. K., Pizza, T., Di Pace, P., De Martino, P., Poppitz, W., Poupaert, J. H., & Lambert, D. M. (2006). Synthesis and activity of 1,3,5-triphenylimidazolidine-2,4-diones and 1,3,5-triphenyl-2-thioxoimidazolidin-4-ones: characterization of new CB1 cannabinoid receptor inverse agonists/antagonists. Journal of Medicinal Chemistry, 49(3), 872-82.
Muccioli GG, et al. Synthesis and Activity of 1,3,5-triphenylimidazolidine-2,4-diones and 1,3,5-triphenyl-2-thioxoimidazolidin-4-ones: Characterization of New CB1 Cannabinoid Receptor Inverse Agonists/antagonists. J Med Chem. 2006 Feb 9;49(3):872-82. PubMed PMID: 16451053.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis and activity of 1,3,5-triphenylimidazolidine-2,4-diones and 1,3,5-triphenyl-2-thioxoimidazolidin-4-ones: characterization of new CB1 cannabinoid receptor inverse agonists/antagonists. AU - Muccioli,Giulio G, AU - Wouters,Johan, AU - Charlier,Caroline, AU - Scriba,Gerhard K E, AU - Pizza,Teresa, AU - Di Pace,Pierluigi, AU - De Martino,Paolo, AU - Poppitz,Wolfgang, AU - Poupaert,Jacques H, AU - Lambert,Didier M, PY - 2006/2/3/pubmed PY - 2006/3/30/medline PY - 2006/2/3/entrez SP - 872 EP - 82 JF - Journal of medicinal chemistry JO - J Med Chem VL - 49 IS - 3 N2 - 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. SN - 0022-2623 UR - https://www.unboundmedicine.com/medline/citation/16451053/Synthesis_and_activity_of_135_triphenylimidazolidine_24_diones_and_135_triphenyl_2_thioxoimidazolidin_4_ones:_characterization_of_new_CB1_cannabinoid_receptor_inverse_agonists/antagonists_ L2 - https://doi.org/10.1021/jm050484f DB - PRIME DP - Unbound Medicine ER -