N-ethyl-4,5-dihydroxy-8-methyl-2-oxo-N-phenyl-1H-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-4,5-dihydroxy-8-methyl-2-oxo-N-phenyl-1H-quinoline-3-carboxamide
• 化学式: C₁₉H₁₈N₂O₄
• 分子量: 338.4
• InChiKey: SIDVMVNDMYXFHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  89.9
• 氢给体数：
  3
• 氢受体数：
  4

文献信息

• CRYSTALS OF LAQUINIMOD SODIUM AND IMPROVED PROCESS FOR THE MANUFACTURE THEREOF
  申请人：Teva Pharmaceutical Industries Ltd.

  公开号：EP2970129A2

  公开（公告）日：2016-01-20
• [EN] CRYSTALS OF LAQUINIMOD SODIUM AND IMPROVED PROCESS FOR THE MANUFACTURE THEREOF<br/>[FR] CRISTAUX DE SODIUM DE LAQUINIMOD ET PROCÉDÉ AMÉLIORÉ POUR LEUR FABRICATION
  申请人：TEVA PHARMA

  公开号：WO2014153145A2

  公开（公告）日：2014-09-25

  The subject invention provides a mixture of crystalline laquinimod sodium particles, wherein (i) ≥ 90% of the total amount by volume of the laquinimod sodium particles have a size of ≤ 40 μm or (ii) ≥ 50% of the total amount by volume of the laquinimod sodium particles have a size of ≤ 15 μm, and wherein: a) the mixture has a bulk density of 0.2-0.4 g/mL; b) the mixture has a tapped density of 0.40-0.7 g/mL; c) an amount of heavy metal in the mixture is no more than 20ppm relative to the amount by weight of laquinimod sodium; d) an amount of MCQ in the mixture is no more than 0.15% relative to the amount of laquinimod sodium as measured by HPLC; e) an amount of MCQCA in the mixture is no more than 0.15% relative to the amount of laquinimod sodium as measured by HPLC; or f) an amount of MCQME in the mixture is no more than 0.12% relative to the amount of laquinimod sodium as measured by HPLC. The subject invention also provides a pharmaceutical composition comprising an amount of laquinimod and at least one of BH-3-HLAQ, MCQ, MCQCA, MCQME, NEA, and MCQEE. The subject invention also provides processes for preparing BH-3-HLAQ, MCQ, MCQCA, MCQME, MCQEE, and compounds prepared by said processes. Further provided is a process for testing whether a sample of laquinimod contains an undesirable impurity. Further provided isp a process for preparing a validated pharmaceutical composition comprising laquinimod, for preparing a pharmaceutical composition comprising laquinimod, or for distributing a validated batch of a pharmaceutical composition comprising laquinimod, for validating a batch of a pharmaceutical product containing laquinimod and a pharmaceutically acceptable carrier for distribution, and for preparing a packaged pharmaceutical composition comprising laquinimod, each comprising determining the amount of at least one of BH-3-HLAQ, MCQ, MCQCA, MCQME, NEA, and MCQEE in a sample or batch. The subject invention further provides use of BH-3-HLAQ, MCQ, MCQCA, MCQME, MCQEE as a reference standard to detect trace amounts of the impurity in a pharmaceutical composition comprising laquinimod. Finally, the subject invention provides methods of ddenrrining the concentration of BH-3- HLAQ, MCQ, MCQCA, MCQME, MCQEE, 5-HLAQ, SPIRO-LAQ or 3 H-LAQ in a pharmaceutical composition comprising laquinimod.