Synthesis and in vitro evaluation of novel 2-oxo-1,2-dihydroquinoline CB2 receptor inverse agonists.
Aliphatic amides of 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid 6 were synthesized and evaluated for their CB2 and CB1 receptor activities by a [35S]GTPgammaS membrane-binding assay. Compounds 7-18 produced CB2 inverse agonist activities with a variety of potencies (IC50: 1 nm-1 microm). By contrast, no considerable antagonism of CB1 receptor was observed by 1-10 microm concentrations indicating that synthesized compounds were CB2 receptor selective.
Raitio
Katri H
KH
Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FI-70211 Kuopio, Finland. katri.raitio@uku.fi
Savinainen
Juha R
JR
Nevalainen
Tapio
T
Järvinen
Tomi
T
Vepsäläinen
Jouko
J
D000818:Animals; D006801:Humans; D006912:Hydroxyquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors*
D006912:Hydroxyquinolines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2