Synthesis and biological evaluation of new 1,2-dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for treatment of autoimmune disorders:: Structure-activity relationship
Synthesis and biological evaluation of new 1,2-dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for treatment of autoimmune disorders:: Structure-activity relationship
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DOI：
10.1021/jm031044w
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发表时间：
2004-04-08
影响因子：
7.3
通讯作者：
Björk, A
中科院分区：
文献类型：
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作者：
Jönsson, S;Andersson, G;Björk, A
制备了罗喹肟相关的3-喹啉甲酰胺衍生物，并评价了其治疗自身免疫性疾病的效果。在小鼠中测试化合物对急性实验性自身免疫性脑脊髓炎模型中疾病发展的抑制作用，并在比格犬中测试所选化合物对促炎反应的诱导作用。结构-活性关系进行了讨论。与先导化合物罗喹美司（1b，Linomide）相比，化合物8 c，拉喹莫德，显示出改善的效力和上级毒理学特性，并被选择用于临床研究（目前处于II期）。
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).