5-chloro-4-(hydroxymethyl)-1H-quinolin-2-one

• 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: 5-chloro-4-(hydroxymethyl)-1H-quinolin-2-one
• 化学式: C₁₀H₈ClNO₂
• 分子量: 209.63
• InChiKey: ITFNPVUOKXDCDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

文献信息

• CRYSTALS OF LAQUINIMOD SODIUM AND IMPROVED PROCESS FOR THE MANUFACTURE THEREOF
  申请人：FEWNKEL Anton

  公开号：US20160046582A1

  公开（公告）日：2016-02-18

  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 20 ppm 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-HKAQ, MCQ, MCQCA, MCQME, NEA, and MCQEE. The subject invention also provides processes for preparing BH-3-HLAQ, MCQ, MCQCA, 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 is 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-HLAO, MCQ, MCQCA, MCQME

  本发明提供了一种晶体LAquinimod钠颗粒的混合物，其中（i）≧90％的LAquinimod钠颗粒的总体积具有≦40μm的尺寸或（ii）≧50％的LAquinimod钠颗粒的总体积具有≦15μm的尺寸，其中：a）混合物的堆积密度为0.2-0.4 g/mL；b）混合物的振实密度为0.40-0.7 g/mL；c）混合物中重金属的量相对于LAquinimod钠的重量不超过20 ppm；d）混合物中MCQ的量相对于用HPLC测量的LAquinimod钠的量不超过0.15％；e）混合物中MCQCA的量相对于用HPLC测量的LAquinimod钠的量不超过0.15％；或f）混合物中MCQME的量相对于用HPLC测量的LAquinimod钠的量不超过0.12％。本发明还提供了一种制药组合物，包括LAquinimod的量和至少一种BH-3-HKAQ、MCQ、MCQCA、MCQME、NEA和MCQEE。本发明还提供了制备BH-3-HLAQ、MCQ、MCQCA、MCQEE和通过该过程制备的化合物的过程。此外，本发明还提供了一种测试LAquinimod样品是否含有不良杂质的过程。本发明还提供了一种制备经过验证的LAquinimod制剂的过程，用于制备包含LAquinimod的制剂，或用于分发经过验证的包含LAquinimod的制剂批次，用于验证包含LAquinimod和药用载体进行分发的药物制品批次，并用于制备包装的包含LAquinimod的制剂，每个过程都包括确定样品或批次中至少一种BH-3-HLAO、MCQ、MCQCA、MCQME、NEA和MCQEE的量。本发明还提供了将BH-3-HLAQ、MCQ、MCQCA、MCQME、MCQEE用作参考标准，以检测含有LAquinimod的制剂中微量杂质的用途。最后，本发明提供了一种确定药物制剂中BH-3-HLAQ、MCQ、MCQCA、MCQME、MCQE<5-HLAQ、SPIRO-LAQ或H-LAQ浓度的方法。