Within our studies on structureeactivity relationships of 4-quinolone-3-carboxamides as cannabinoid ligands, a new series of compounds characterized by a fluoro or phenylthio group at 7-position and different substituents at N1 and carboxamide nitrogen were synthesized and evaluated for their binding ability to cannabinoid type 1 (CB1) and type 2 (CB2) receptors. Most of the compounds showed affinity for one or both cannabinoid receptors at nanomolar concentration, with Ki(CB1) and Ki(CB2) values ranging from 2.45 to >10,000 nM and from 0.09 to 957 nM, respectively. The N-(3,4-dichlorobenzyl) amide derivatives 27 and 40 displayed relatively low affinity, but high selectivity towards the CB1 receptor. Compounds 4 and 40, a CB2 and a CB1 ligand, respectively, behaved as partial agonists in the [35S]GTPgS assay. They showed very low permeability through (MDCK-MDR1) cells and might, therefore, represent possible lead structures for further optimization in the search for cannabinoid ligands unable to cross the bloodebrain barrier

Pasquini, S., De Rosa, M., Ligresti, A., Mugnaini, C., Brizzi, A., Caradonna, N.P., et al. (2012). Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 6. Synthesis and Pharmacological Evaluation of 7-Substituted 4-Quinolone-3-carboxamide Derivatives as High Affinity Ligands for Cannabinoid Receptors. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 58, 30-43 [10.1016/j.ejmech.2012.09.035].

Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 6. Synthesis and Pharmacological Evaluation of 7-Substituted 4-Quinolone-3-carboxamide Derivatives as High Affinity Ligands for Cannabinoid Receptors

Pasquini, Serena;De Rosa, Maria;Mugnaini, Claudia;Brizzi, Antonella;Corelli, Federico
2012-01-01

Abstract

Within our studies on structureeactivity relationships of 4-quinolone-3-carboxamides as cannabinoid ligands, a new series of compounds characterized by a fluoro or phenylthio group at 7-position and different substituents at N1 and carboxamide nitrogen were synthesized and evaluated for their binding ability to cannabinoid type 1 (CB1) and type 2 (CB2) receptors. Most of the compounds showed affinity for one or both cannabinoid receptors at nanomolar concentration, with Ki(CB1) and Ki(CB2) values ranging from 2.45 to >10,000 nM and from 0.09 to 957 nM, respectively. The N-(3,4-dichlorobenzyl) amide derivatives 27 and 40 displayed relatively low affinity, but high selectivity towards the CB1 receptor. Compounds 4 and 40, a CB2 and a CB1 ligand, respectively, behaved as partial agonists in the [35S]GTPgS assay. They showed very low permeability through (MDCK-MDR1) cells and might, therefore, represent possible lead structures for further optimization in the search for cannabinoid ligands unable to cross the bloodebrain barrier
2012
Pasquini, S., De Rosa, M., Ligresti, A., Mugnaini, C., Brizzi, A., Caradonna, N.P., et al. (2012). Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 6. Synthesis and Pharmacological Evaluation of 7-Substituted 4-Quinolone-3-carboxamide Derivatives as High Affinity Ligands for Cannabinoid Receptors. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 58, 30-43 [10.1016/j.ejmech.2012.09.035].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/41590
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