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Novel 4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives as new CB2 cannabinoid receptors agonists: synthesis, pharmacological properties and molecular modeling.
J Med Chem. 2006 Jan 12; 49(1):70-9.JM

Abstract

Recent data indicated that the CB(2) cannabinoid receptor constitutes an attractive drug target due to its potential functional role in several physiological and pathological processes. A set of 4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives, characterized by the presence of some important structural requirements exhibited by other classes of cannabinoid ligands, such as an aliphatic or aromatic carboxamide group in position 3, and an alkyl or benzyl group in position 1, was synthesized and assayed to measure their respective affinity for both human CB(1) and CB(2) cannabinoid receptors. The results indicate that these 3-carboxamido-quinolones derivatives exhibited a CB(2) receptor selectivity, particularly derivatives 28-30, and 32R. Moreover, in the [(35)S]-GTPgammaS binding assay, all the compounds behaved as CB(2) receptor agonists. Molecular modeling studies showed that compound 30 interacts with the CB(2) receptor through a combination of hydrogen bond and aromatic/hydrophobic interactions. In conclusion, 4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives constitute a new class of potent and selective CB(2) cannabinoid receptors agonists.

Authors+Show Affiliations

Institut de Chimie Pharmaceutique Albert Lespagnol, Université de Lille 2, EA 2692, 3 rue du Pr. Laguesse, B.P. 83, F-59006 Lille, France.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

16392793

Citation

Stern, Eric, et al. "Novel 4-oxo-1,4-dihydroquinoline-3-carboxamide Derivatives as New CB2 Cannabinoid Receptors Agonists: Synthesis, Pharmacological Properties and Molecular Modeling." Journal of Medicinal Chemistry, vol. 49, no. 1, 2006, pp. 70-9.
Stern E, Muccioli GG, Millet R, et al. Novel 4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives as new CB2 cannabinoid receptors agonists: synthesis, pharmacological properties and molecular modeling. J Med Chem. 2006;49(1):70-9.
Stern, E., Muccioli, G. G., Millet, R., Goossens, J. F., Farce, A., Chavatte, P., Poupaert, J. H., Lambert, D. M., Depreux, P., & Hénichart, J. P. (2006). Novel 4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives as new CB2 cannabinoid receptors agonists: synthesis, pharmacological properties and molecular modeling. Journal of Medicinal Chemistry, 49(1), 70-9.
Stern E, et al. Novel 4-oxo-1,4-dihydroquinoline-3-carboxamide Derivatives as New CB2 Cannabinoid Receptors Agonists: Synthesis, Pharmacological Properties and Molecular Modeling. J Med Chem. 2006 Jan 12;49(1):70-9. PubMed PMID: 16392793.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel 4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives as new CB2 cannabinoid receptors agonists: synthesis, pharmacological properties and molecular modeling. AU - Stern,Eric, AU - Muccioli,Giulio G, AU - Millet,Régis, AU - Goossens,Jean-François, AU - Farce,Amaury, AU - Chavatte,Philippe, AU - Poupaert,Jacques H, AU - Lambert,Didier M, AU - Depreux,Patrick, AU - Hénichart,Jean-Pierre, PY - 2006/1/6/pubmed PY - 2006/2/17/medline PY - 2006/1/6/entrez SP - 70 EP - 9 JF - Journal of medicinal chemistry JO - J Med Chem VL - 49 IS - 1 N2 - Recent data indicated that the CB(2) cannabinoid receptor constitutes an attractive drug target due to its potential functional role in several physiological and pathological processes. A set of 4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives, characterized by the presence of some important structural requirements exhibited by other classes of cannabinoid ligands, such as an aliphatic or aromatic carboxamide group in position 3, and an alkyl or benzyl group in position 1, was synthesized and assayed to measure their respective affinity for both human CB(1) and CB(2) cannabinoid receptors. The results indicate that these 3-carboxamido-quinolones derivatives exhibited a CB(2) receptor selectivity, particularly derivatives 28-30, and 32R. Moreover, in the [(35)S]-GTPgammaS binding assay, all the compounds behaved as CB(2) receptor agonists. Molecular modeling studies showed that compound 30 interacts with the CB(2) receptor through a combination of hydrogen bond and aromatic/hydrophobic interactions. In conclusion, 4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives constitute a new class of potent and selective CB(2) cannabinoid receptors agonists. SN - 0022-2623 UR - https://www.unboundmedicine.com/medline/citation/16392793/Novel_4_oxo_14_dihydroquinoline_3_carboxamide_derivatives_as_new_CB2_cannabinoid_receptors_agonists:_synthesis_pharmacological_properties_and_molecular_modeling_ L2 - https://doi.org/10.1021/jm050467q DB - PRIME DP - Unbound Medicine ER -