ABR-215174

• 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: ABR-215174
• 英文别名: (N-phenyl-5-chloro-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide)；5-chloro-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-N-phenyl-3-quinolinecarboxamide；N-phenyl-5-chloro-1,2-dihydro-4-hydroxy-1-methyl-2-oxoquinoline-3-carboxamide；IMA-06201；5-chloro-4-hydroxy-1-methyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide；5-chloro-4-hydroxy-1-methyl-2-oxo-N-phenylquinoline-3-carboxamide
• 化学式: C₁₇H₁₃ClN₂O₃
• 分子量: 328.755
• InChiKey: BZKCTVZVKAXVFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

5-氯-4-羟基-1-甲基-2-氧代-N-苯基-1,2-二氢喹啉-3-甲酰胺是拉喹尼莫德已知的人体代谢物。

5-chloro-4-hydroxy-1-methyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide is a known human metabolite of laquinimod.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  ABR-215174 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 以251 mg的产率得到5-chloro-4-hydroxy-1-methyl-2-oxo-N-phenyl-quinoline-3-carboxamide potassium salt
  参考文献：
  名称：

  US2023/167064

  摘要：

  公开号：
• 作为产物：
  描述：

  5-氯-1,2-二氢-4-羟基-1-甲基-2-氧代-3-喹啉羧酸乙酯 以 正庚烷 、 甲苯 为溶剂， 反应 7.68h， 生成 ABR-215174
  参考文献：
  名称：

  拉喹莫德，喹啉-3-羧酰胺的合成和反应性：烯醇质子到氮原子的分子内转移作为可能的乙烯形成机理。

  摘要：

  5-氯-N-乙基-1,2-二氢-4-羟基-1-甲基-2-氧代-N-苯基-3-喹啉甲酰胺（laquinimod，2）是临床试验中的口服药物，可用于治疗多种硬化。合成2的最后一步是酯1与N-乙基苯胺的高产氨解反应。在1和2之间存在平衡，并且在反应过程中除去生成的甲醇是从1获得2的高收率的先决条件。1和2的反应性用力学模型解释了该机理，该模型涉及烯醇质子转移到环外羰基取代基并伴随形成烯酮3。由于2，由于空间相互作用，使与羰基氧的分子内氢键减弱，因此特别有利于2的质子转移。既1和2经历solvolosis反应服从一级反应动力学，进一步支持该理论认为这两种分子都能够单分子分解成烯酮3。的依赖于溶剂的分光设有2表明该分子主要存在于两个构象中。一种构象在非极性溶剂中是有利的，并且可能是分子内氢键合的结果。在极性溶剂中有利于另一种构象，并且可能表现出较少的分子内氢键。

  DOI：

  10.1021/jo052368q

文献信息

• DEUTERATED N-ETHYL-N-PHENYL-1,2-DIHYDRO-4-HYDROXY-5-CHLORO-1-METHYL-2-OXOQUINOLINE-3-CARBOXAMIDE, SALTS AND USES THEREOF
  申请人：Piryatinsky Victor

  公开号：US20120010238A1

  公开（公告）日：2012-01-12

  The subject invention provides deuterated N-ethyl-N-phenyl-1,2-dihydro-4-hydroxy-5-chloro-1-methyl-2-oxoquinoline-3-carboxamide, its salts and uses.

  该发明提供了重氢化N-乙基-N-苯基-1,2-二氢-4-羟基-5-氯-1-甲基-2-氧基喹啉-3-羧酰胺，其盐和用途。
• [EN] PROCESS FOR THE MANUFACTURE OF QUINOLINE DERIVATIVES<br/>[FR] METHODE DE PRODUCTION DE DERIVES DE QUINOLINE
  申请人：ACTIVE BIOTECH AB

  公开号：WO2003106424A1

  公开（公告）日：2003-12-24

  A process for the preparation of the compounds of general formula (I); by reacting a quinoline-3-carboxylic acid ester derivative of formula A with an aniline derivative of formula B in a solvent selected from straight- or branch-chaineded alkanes and cycloalkanes or mixtures thereof with a boiling point between 80 and 200 C.

  一种制备通式（I）化合物的方法；通过在直链或支链烷烃和环烷烃或其混合物中选择沸点在80到200摄氏度之间的溶剂，将式A的喹啉-3-羧酸酯衍生物与式B的苯胺衍生物反应。
• 5-CHLORO-4-HYDROXY-1-METHYL-2-OXO-N-PHENYL-1,2-DIHYDROQUINOLINE-3-CARBOXAMIDE, SALTS AND USES THEREOF
  申请人：Fristedt Ulf Tomas

  公开号：US20120010239A1

  公开（公告）日：2012-01-12

  The subject invention provides 5-chloro-4-hydroxy-1-methyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide, its salts and uses.

  本发明提供了5-氯-4-羟基-1-甲基-2-氧代-N-苯基-1,2-二氢喹啉-3-羧酰胺及其盐和用途。
• 1,2-DIHYDRO-4-HYDROXY-2-OXO-QUINOLINE-3-CARBOXANILIDES AS AHR ACTIVATORS
  申请人：Pettersson Lars

  公开号：US20130203703A1

  公开（公告）日：2013-08-08

  The present invention relates to compounds which are 1,2-dihydro-4-hydroxy-2-oxo-quinoline-3-carboxanilides, their thieno-pyridone analogs, and prodrugs thereof. This invention specifically relates to such derivatives containing an N-hydrogen in the carboxanilide moiety and which exhibit modulating activity towards the aromatic hydrocarbon receptor (AhR), and, specifically, also to prodrugs thereof. The present invention also relates to use of said compounds as a medicament, and for the treatment of cancer, autoimmune disorders and other disorders with an immunological component, and a pharmaceutical composition comprising one or more of said compounds and a method of treatment.

  本发明涉及1,2-二氢-4-羟基-2-氧代-喹啉-3-羧酰苯胺类化合物、其噻吩-吡啶酮类似物以及它们的前药。本发明具体涉及含有羧酰苯胺基团中的N-氢的衍生物，它们表现出对芳香族碳氢受体（AhR）的调节活性，以及它们的前药。本发明还涉及所述化合物作为药物的用途，用于治疗癌症、自身免疫性疾病以及其他具有免疫学成分的疾病，以及一种包含一种或多种所述化合物的药物组合物和一种治疗方法。
• 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。