Pharmacomodulations around the 4-Oxo-1,4-dihydroquinoline-3-carboxamides, a Class of Potent CB2-Selective Cannabinoid Receptor Ligands:  Consequences in Receptor Affinity and Functionality

CB2 receptor selective ligands are becoming increasingly attractive drugs due to the potential role of this receptor in several physiopathological processes. Thus, the development of our previously described series of 4-oxo-1,4-dihydroquinoline-3-carboxamides was pursued with the aim to further char...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2007-11, Vol.50 (22), p.5471-5484
Main Authors: Stern, Eric, Muccioli, Giulio G, Bosier, Barbara, Hamtiaux, Laurie, Millet, Régis, Poupaert, Jacques H, Hénichart, Jean-Pierre, Depreux, Patrick, Goossens, Jean-François, Lambert, Didier M
Format: Article
Language:English
Subjects:
Amides - chemical synthesis
Amides - chemistry
Amides - pharmacology
Animals
Binding, Competitive
Biological and medical sciences
CHO Cells
Cricetinae
Cricetulus
Drug Inverse Agonism
Humans
Ligands
Medical sciences
Miscellaneous
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Quinolines - chemical synthesis
Quinolines - chemistry
Quinolines - pharmacology
Radioligand Assay
Receptor, Cannabinoid, CB2 - agonists
Receptor, Cannabinoid, CB2 - antagonists & inhibitors
Stereoisomerism
Structure-Activity Relationship
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Summary:CB2 receptor selective ligands are becoming increasingly attractive drugs due to the potential role of this receptor in several physiopathological processes. Thus, the development of our previously described series of 4-oxo-1,4-dihydroquinoline-3-carboxamides was pursued with the aim to further characterize the structure−affinity and structure−functionality relationships of these derivatives. The influence of the side chain was investigated by synthesizing compounds bearing various carboxamido and keto substituents. On the other hand, the role of the quinoline central scaffold was studied by synthesizing several 6-, 7-, or 8-chloro-4-oxo-1,4-dihydroquinolines, as well as 4-oxo-1,4-dihydronaphthyridine and 4-oxo-1,4-dihydrocinnoline derivatives. The effect of these modifications on the affinity and functionality at the CB2 receptor was studied and allowed for the characterization of new selective CB2 receptor ligands.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm070387h