ethyl 1,2-dihydro-4-hydroxy-1-methyl-5-nitro-2-oxo-3-quinolinecarboxylate | 675574-92-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: ethyl 1,2-dihydro-4-hydroxy-1-methyl-5-nitro-2-oxo-3-quinolinecarboxylate
• 英文别名: 3-Quinolinecarboxylic acid,1,2-dihydro-4-hydroxy-1-methyl-5-nitro-2-oxo-,ethyl ester；ethyl 4-hydroxy-1-methyl-5-nitro-2-oxoquinoline-3-carboxylate
• CAS: 675574-92-2
• 化学式: C₁₃H₁₂N₂O₆
• 分子量: 292.248
• InChiKey: QELGMVMFXFOCOD-UHFFFAOYSA-N

物化性质

• 沸点：
  454.7±45.0 °C(Predicted)
• 密度：
  1.490±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 1,2-dihydro-4-hydroxy-1-methyl-5-nitro-2-oxo-3-quinolinecarboxylate 在 盐酸 作用下， 以 溶剂黄146 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  Synthesis and Biological Evaluation of New 1,2-Dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for Treatment of Autoimmune Disorders:  Structure−Activity Relationship

  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).

  DOI：

  10.1021/jm031044w
• 作为产物：
  描述：

  6-硝基靛红酸酐 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 ethyl 1,2-dihydro-4-hydroxy-1-methyl-5-nitro-2-oxo-3-quinolinecarboxylate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of New 1,2-Dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for Treatment of Autoimmune Disorders:  Structure−Activity Relationship

  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).

  DOI：

  10.1021/jm031044w

文献信息

• Quinoline derivatives
  申请人：Active Biotech AB

  公开号：US06605616B1

  公开（公告）日：2003-08-12

  The invention is related to compounds of general formula (I) wherein R is methyl, ethyl, n-propyl, iso-propyl, n-butyl or allyl; R′ is methyl, methoxy, fluoro, chloro, bromo, azido, trifluorometlhyl, or OCHxFy, wherein x=0−2, y=1−3 with the. proviso that x+y=3; R″ is hydrogen, fluoro or chloro; with the proviso that R″ is fluoro or chloro only when R′ is fluoro or chloro; R4 is hydrogen or pharmaceutically acceptable inorganic or organic cations; R5 is dimethylamino or nitro; R6 is hydrogen; and when R′ is azido R5 is also ethyl, n-propyl, iso-propyl, methoxy, ethoxy, chloro, bromo, trifluoromethyl, OCHxFy, wherein x=0−2, y=1−3 with the proviso that x+y=3, or R5 and R6 taken together are methylenedioxy; and any tautomer thereof. The invention also relates to pharmaceutical compositions containing a compound of the general formula (I) together with a pharmaceutically acceptable carrier. Included are also processes for the preparation of the compounds of formula (I), as well as methods for the treatment of mammals suffering from diseases resulting from autoimmunity and pathological inflammation by administering of a compound having the formula (I) to said mammal.

  该发明涉及通式（I）的化合物，其中R为甲基、乙基、正丙基、异丙基、正丁基或烯丙基；R′为甲基、甲氧基、氟、氯、溴、偶氮、三氟甲基或OCHxFy，其中x＝0−2，y＝1−3，但有条件x＋y＝3；R″为氢、氟或氯；有条件R″仅在R′为氟或氯时为氟或氯；R4为氢或药学上可接受的无机或有机阳离子；R5为二甲氨基或硝基；R6为氢；当R′为偶氮时，R5也可以是乙基、正丙基、异丙基、甲氧基、乙氧基、氯、溴、三氟甲基、OCHxFy，其中x＝0−2，y＝1−3，但有条件x＋y＝3，或R5和R6结合成亚甲二氧基；以及其任何互变异构体。该发明还涉及含有通式（I）的化合物和药学上可接受的载体的制药组合物。还包括通式（I）化合物的制备过程，以及通过给予具有通式（I）的化合物治疗患有由自身免疫和病理性炎症引起的疾病的哺乳动物的方法。
• US6605616B1
  申请人：——

  公开号：US6605616B1

  公开（公告）日：2003-08-12
• Synthesis and Biological Evaluation of New 1,2-Dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for Treatment of Autoimmune Disorders:  Structure−Activity Relationship
  作者：Stig Jönsson、Gunnar Andersson、Tomas Fex、Tomas Fristedt、Gunnar Hedlund、Karl Jansson、Lisbeth Abramo、Ingela Fritzson、Olga Pekarski、Anna Runström、Helena Sandin、Ingela Thuvesson、Anders Björk

  DOI：10.1021/jm031044w

  日期：2004.4.1

  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).