Synthesis and biological evaluation of new 1,2-dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for treatment of autoimmune disorders:: Structure-activity relationship

被引：141
|
作者：
Jönsson, S [1 ]
Andersson, G [1 ]
Fex, T [1 ]
Fristedt, T [1 ]
Hedlund, G [1 ]
Jansson, K [1 ]
Abramo, L [1 ]
Fritzson, I [1 ]
Pekarski, O [1 ]
Runström, A [1 ]
Sandin, H [1 ]
Thuvesson, I [1 ]
Björk, A [1 ]
机构：
[1] Active Biotech Res AB, SE-22007 Lund, Sweden
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 08期
关键词：
D O I：
10.1021/jm031044w
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Roquinimex-related 3-quinolinecarboxamide derivatives were prepared and evaluated for treatment of autoimmune disorders. The compounds were tested in mice for their inhibitory effects on disease development in the acute experimental autoimmune encephalomyelitis model and selected compounds in the beagle dog for induction of proinflammatory reaction. Structure-activity relationships are discussed. Compound 8c, laquinimod, showed improved potency and superior toxicological profile compared to the lead compound roquinimex (1b, Linomide) and was selected for clinical studies (currently in phase II).
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收藏
页码：2075 / 2088
页数：14
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