N-ethyl-N-phenyl-1,2-dihydro-1,5-dimethyl-4-hydroxy-2-oxo-quinoline-3-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-ethyl-N-phenyl-1,2-dihydro-1,5-dimethyl-4-hydroxy-2-oxo-quinoline-3-carboxamide
• 英文别名: N-ethyl-N-phenyl-1,2-dihydro-4-hydroxy-1,5-dimethyl-2-oxo-quinoline-3-carboxamide；N-ethyl-4-hydroxy-1,5-dimethyl-2-oxo-N-phenylquinoline-3-carboxamide
• 化学式: C₂₀H₂₀N₂O₃
• 分子量: 336.39
• InChiKey: NNDZSFODGTZLGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  60.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氨基-6-甲基苯甲酸 在 sodium hydride 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 17.0h， 生成 N-ethyl-N-phenyl-1,2-dihydro-1,5-dimethyl-4-hydroxy-2-oxo-quinoline-3-carboxamide
  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

• [EN] QUINOLINE DERIVATIVES<br/>[FR] DERIVES DE QUINOLINE
  申请人：ACTIVE BIOTECH AB

  公开号：WO1999055678A1

  公开（公告）日：1999-11-04

  (EN) The invention relates to compounds of general formula (I) wherein R is selected from ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec.-butyl and allyl; R4 is selected from hydrogen and pharmaceutically acceptable inorganic and organic cations; R5 is selected from methyl, ethyl, n-propyl, iso-propyl, methoxy, ethoxy, chloro, bromo, CF3, and OCHxFy; wherein x = 0 - 2, y = 1 - 3 with the proviso that x + y = 3; R6 is hydrogen; or R5 and R6 taken together are methylenedioxy; and any tautomer thereof. The invention also relates to pharmaceutical compositions containing a compound of 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 of treating mammals suffering from diseases resulting from autommunity and pathological inflammation by administrering a compound having formula (I) to said mammal.(FR) L'invention concerne des composés de la formule générale (I) où R est sélectionné parmi l'éthyle, n-propyle, iso-propyle, n-butyle, iso-butyle, sec.-butyle et allyle; R4 est choisi parmi l'hydrogène et des cations organiques et anorganiques pharmaceutiquement acceptables ; R5 est choisi parmi le méthyle, éthyle, n-propyle, iso-propyle, métoxy, éthoxy, chlore, brome, CF3 et OCHxFy; x = 0 - 2, y = 1 - 3 à condition que x + y = 3 ; R6 représente de l'hydrogène ; Ou R5 et R6 ensemble représentent du méthylèndioxy ; et n'importe quel de ses tautomère. L'invention concerne également des compositions pharmaceutiques contenant un composé de la formule générale (I) et un excipient pharmaceutiquement acceptable. L'invention concerne des procédés de préparation des composés de la formule (I) ainsi que des procédés de traitement de mammifères souffrant de maladies résultant d'une inflammation auto-immune et pathologique par administration audit mammifère d'un composé ayant la formule (I).

  该发明涉及一般式(I)的化合物，其中R选自乙基、正丙基、异丙基、正丁基、异丁基、仲丁基和烯丙基；R4选自氢和药学上可接受的无机和有机阳离子；R5选自甲基、乙基、正丙基、异丙基、甲氧基、乙氧基、氯、溴、CF3和OCHxFy；其中x = 0-2，y = 1-3，前提是x + y = 3；R6为氢；或者R5和R6在一起是亚甲二氧基；以及其任何互变异构体。该发明还涉及含有一般式(I)的化合物和药学上可接受的载体的药物组成物。还包括制备式(I)化合物的方法，以及通过将具有式(I)的化合物用于治疗因自身免疫和病理性炎症引起的哺乳动物患病的方法。
• QUINOLINE DERIVATIVES
  申请人：Active Biotech AB

  公开号：EP1073639A1

  公开（公告）日：2001-02-07
• DRUGS FOR THE TREATMENT OF MALIGNANT TUMOURS
  申请人：Active Biotech AB

  公开号：EP1224172A1

  公开（公告）日：2002-07-24
• US6077851A
  申请人：——

  公开号：US6077851A

  公开（公告）日：2000-06-20
• US6395750B1
  申请人：——

  公开号：US6395750B1

  公开（公告）日：2002-05-28