Abstract
Experimental evidence suggests that selective CB2 receptor modulators may provide access to antihyperalgesic agents devoid of psychotropic effects. Taking advantage of previous findings on structure-activity/selectivity relationships for a class of 4-quinolone-3-carboxamides, further structural modifications of the heterocyclic scaffold were explored, leading to the discovery of the 8-methoxy derivative 4a endowed with the highest affinity and selectivity ever reported for a CB2 ligand. The compound, evaluated in vivo in the formalin test, behaved as an inverse agonist by reducing at a dose of 6 mg/kg the second phase of the formalin-induced nocifensive response in mice.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4-Quinolones / chemical synthesis
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4-Quinolones / metabolism
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4-Quinolones / pharmacology*
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Adamantane / analogs & derivatives*
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Adamantane / chemical synthesis
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Adamantane / metabolism
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Adamantane / pharmacology
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Analgesics / pharmacology
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Animals
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Cell Survival / drug effects
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Hep G2 Cells
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Humans
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Ligands
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Mice
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Quinolones / chemical synthesis
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Quinolones / metabolism
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Quinolones / pharmacology*
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Rats
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Receptor, Cannabinoid, CB2 / drug effects
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Receptor, Cannabinoid, CB2 / metabolism*
Substances
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4-Quinolones
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Analgesics
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Ligands
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N-(adamantan-1-yl)-8-methoxy-4-oxo-1-pentyl-1,4-dihydroquinoline-3-carboxamide
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Quinolones
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Receptor, Cannabinoid, CB2
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Adamantane