Synthesis and SAR studies of 2-oxoquinoline derivatives as CB2 receptor inverse agonists

被引:61
作者
Raitio, KH
Savinainen, JR
Vepsäläinen, J
Laitinen, JT
Poso, A
Järvinen, T
Nevalainen, T
机构
[1] Univ Kuopio, Dept Pharmaceut Chem, Dept Physiol, FI-70211 Kuopio, Finland
[2] Univ Kuopio, Dept Chem, FI-70211 Kuopio, Finland
关键词
D O I
10.1021/jm050879z
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The highly CB2 selective cannabinoid receptor inverse agonist, 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid N-benzo[1,3]dioxol-5-ylmethyl)amide (JTE-907; 9b), served as the lead compound for investigating the structure-activity relationships of its analogues and in the search for more potent and effective CB2 receptor inverse agonists. A series of aromatic amides of 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid 6 was synthesized, and the CB2 receptor activities of the compounds were determined by a [S-35]GTP(gamma)S-binding assay using membranes of CHO cells stably transfected with the human CB2 receptor. As a result, all the compounds were defined as full CB2 receptor inverse agonists, and additionally, except for two 3,4-dihydroxyphenylalkylamides, they were found to be equally potent as SR144528.
引用
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页码:2022 / 2027
页数:6
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