达比加群杂质J | 211915-00-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 达比加群杂质J
• 英文名称: methyl-3-[[[2-[[[4-[amino[[[(hexyloxy)carbonyl]imino]methyl]]phenyl]amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl](pyridin-2-yl)amino]propionate
• 英文别名: methyl 3-{[(2-{[(4-{[(hexyloxy)carbonyl]carbamimidoyl}phenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl](pyridin-2-yl)amino}propanoate；Dabigatran iMpurity J；methyl 3-[[2-[[4-(N-hexoxycarbonylcarbamimidoyl)anilino]methyl]-1-methylbenzimidazole-5-carbonyl]-pyridin-2-ylamino]propanoate
• CAS: 211915-00-3
• 化学式: C₃₃H₃₉N₇O₅
• 分子量: 613.717
• InChiKey: JYCBMCKZNSEICQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  45
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  154
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-[[2-[[(4-氰基苯基)氨基]甲基]-1-甲基-1H-苯并咪唑-5-基]羰基]-N-2-吡啶基-beta-丙氨酸 在 盐酸 、 potassium carbonate 作用下， 反应 15.0h， 生成 达比加群杂质J
  参考文献：
  名称：

  Identification, Synthesis, and Strategy for the Reduction of Potential Impurities Observed in Dabigatran Etexilate Mesylate Processes

  摘要：

  Synthetic impurities that are present in dabigatran etexilate mesylate were studied, and possible pathways by which these impurities are formed during the manufacturing process were examined. The impurities were monitored by high-performance liquid chromatography, and their structures were determined by mass spectrometry and H-1 and C-13 NMR. Potential causes for the formation of these impurities are discussed, and strategies to minimize their formation are also described.

  DOI：

  10.1021/op500084q

文献信息

• Disubstituted bicyclic heterocycles, the preparations and the use
  申请人：Boehringer Ingelheim Pharma KG

  公开号：US06087380A1

  公开（公告）日：2000-07-11

  New disubstituted bicyclic heterocycles of general formula R.sub.a --A--Het--B--Ar--E (I) Compounds of the above general formula I, wherein E denotes an R.sub.b NH--C(.dbd.NH)-- group, have valuable pharmacological properties, particularly a thrombin-inhibiting effect and the effect of prolonging thrombin time, and those wherein E denotes a cyano group, are valuable intermediates for preparing the other compounds of general formula I. Exemplary compounds of formula I are: (a) 1-Methyl-2-[N-(4-amidinophenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid-N-phenyl-N-(2-hydroxycarbonylethyl)-amide, (b) 1-Methyl-2-[N-(4-amidinophenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(hydroxycarbonylmethyl)-amide, (c) 1-Methyl-2-[N-(4-amidino-2-methoxy-phenyl)-aminomethyl]-benzimidazol-5-yl- carboxylic acid-N-(2-pyridyl)-N-(hydroxycarbonylmethyl)-amide, and (d) 1-Methyl-2-[N-[4-(N-n-hexyloxycarbonylamidino)phenyl]aminomethyl]-benzimid azol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(2-ethoxycarbonylethyl) amide.

  新的二取代杂环化合物的一般公式为R.sub.a --A--Het--B--Ar--E（I）。上述一般公式I的化合物中，E代表一个R.sub.b NH--C(.dbd.NH)--基团，具有有价值的药理特性，特别是抑制凝血酶的作用和延长凝血酶时间的作用，其中E代表氰基的化合物是制备一般公式I其他化合物的有价值中间体。公式I的示例化合物包括：（a）1-甲基-2-[N-(4-氨基苯基)-氨甲基]-苯并咪唑-5-基-羧酸-N-苯基-N-(2-羟基羰基乙基)-酰胺，（b）1-甲基-2-[N-(4-氨基苯基)-氨甲基]-苯并咪唑-5-基-羧酸-N-(2-吡啶基)-N-(羟基羰基甲基)-酰胺，（c）1-甲基-2-[N-(4-氨基-2-甲氧基苯基)-氨甲基]-苯并咪唑-5-基-羧酸-N-(2-吡啶基)-N-(羟基羰基甲基)-酰胺，和（d）1-甲基-2-[N-[4-(N-己氧羰胺基)苯基]氨甲基]-苯并咪唑-5-基-羧酸-N-(2-吡啶基)-N-(2-乙氧羰基乙基)酰胺。
• Dabigatran etexilate and related substances, processes and compositions, and use of the substances as reference standards and markers
  申请人：Medichem, S.A.

  公开号：EP2522662A1

  公开（公告）日：2012-11-14

  The present invention relates to dabigatran etexilate and related substances and use of the substances as reference standards and markers. There are also provided processes of detecting the substances in samples of dabigatran etexilate, or pharmaceutically acceptable salts or solvates thereof, and also for analyzing the purity of samples of dabigatran etexilate, or pharmaceutically acceptable salts or solvates thereof. There are still further provided processes of preparing dabigatran etexilate and related substances, and pharmaceutical compositions containing the same.

  本发明涉及达比加群酯和相关物质，以及将这些物质用作参考标准和标记物的用途。还提供了检测达比加群酯样品中这些物质的方法，或者这些样品的药用盐或溶剂，以及分析达比加群酯样品的纯度的方法。此外，还提供了制备达比加群酯和相关物质以及含有相同物质的药物组合物的方法。
• [EN] DABIGATRAN ETEXILATE AND RELATED SUBSTANCES, PROCESSES AND COMPOSITIONS, AND USE OF THE SUBSTANCES AS REFERENCE STANDARDS AND MARKERS<br/>[FR] ETÉXILATE DE DABIGATRAN ET SUBSTANCES, PROCÉDÉS ET COMPOSITIONS S'Y RAPPORTANT ET UTILISATION DES SUBSTANCES COMME ÉTALONS DE RÉFÉRENCE ET MARQUEURS
  申请人：MEDICHEM SA

  公开号：WO2012152855A1

  公开（公告）日：2012-11-15

  The present invention relates to dabigatran etexilate and related substances and use of the substances as reference standards and markers. There are also provided processes of detecting the substances in samples of dabigatran etexilate, or pharmaceutically acceptable salts or solvates thereof, and also for analyzing the purity of samples of dabigatran etexilate, or pharmaceutically acceptable salts or solvates thereof.There are still further provided processes of preparing dabigatran etexilate and related substances, and pharmaceutical compositions containing the same.

  本发明涉及达比加群酮乙酸酯及相关物质，以及将这些物质用作参考标准和标记物的用途。还提供了检测达比加群酮乙酸酯样品中这些物质的方法，或者其药学上可接受的盐或溶剂，以及分析达比加群酮乙酸酯样品纯度的方法。还提供了制备达比加群酮乙酸酯及相关物质的方法，以及含有这些物质的药物组合物。
• 一种苯并咪唑甲酯有关物质的制备
  申请人：上海医药工业研究院

  公开号：CN105622576A

  公开（公告）日：2016-06-01

  一种苯并咪唑甲酯有关物质的制备。本发明公开了一种达比加群酯有关物质制备方法及其用途。所述有关物质的结构如式3所示的化合物，可以将结构如式2所示的化合物在缩合剂存在下与甲醇反应而得到。
• Disubstituted bicyclic heterocycles, the preparation thereof, and their use as pharmaceutical compositions
  申请人：Boehringer Ingelheim Pharma GmbH & Co., KG

  公开号：US06710055B2

  公开（公告）日：2004-03-23

  Disubstituted bicyclic heterocycles of general formula I Ra—A—Het—B—Ar—E  (I). Compounds of general formula I, wherein E is an RbNH—C(═NH)— group, have valuable pharmacological properties, particularly a thrombin-inhibiting effect and the effect of prolonging thrombin time, and those wherein E is a cyano group, are valuable intermediates for preparing the other compounds of general formula I.

  通式为IRa—A—Het—B—Ar—E（I）的二取代双环杂环化合物。通式为I的化合物，其中E是RbNH—C(═NH)—基团，具有有价值的药理学特性，特别是抑制凝血酶的作用和延长凝血酶时间的作用，而其中E是氰基的化合物，则是制备通式I的其他化合物的有价值中间体。