达比加群杂质38 | 1415901-83-5

• 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38
• 英文名称: 3-({2-[(4-{amino-[(E)-ethyloxycarbonylimino]methyl}-phenylamino)methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}pyridin-2-yl-amino)propionic acid ethyl ester
• 英文别名: N-EthoxycarbonylDabigatranEthylEster；ethyl 3-[[2-[[4-(N-ethoxycarbonylcarbamimidoyl)anilino]methyl]-1-methylbenzimidazole-5-carbonyl]-pyridin-2-ylamino]propanoate
• CAS: 1415901-83-5；1416446-40-6
• 化学式: C₃₀H₃₃N₇O₅
• 分子量: 571.636
• InChiKey: NROPEVJSKVOJOL-UHFFFAOYSA-N

物化性质

• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  154
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  达比加群杂质38 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 5.0h， 以80%的产率得到3-({2-[(4-{amino-[(E)-ethyloxycarbonylimino]methyl}-phenylamino)methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}pyridin-2-yl-amino)propionic acid
  参考文献：
  名称：

  Synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing a cleavable moiety with anti-platelet activity

  摘要：

  A novel series of prodrugs consisting of dabigatran and 2-hydroxymethyl-3,5,6-trimethylpyrazine (HTMP) were synthesized. The pharmacological results show that all of them possess the effect of anti-platelet aggregation induced by thrombin in vitro. Moreover, one of those compounds, Y-2 (ED50 = 2.1 +/- 1.3 mg/kg) shows more potent activity for inhibiting thrombosis in vivo than that of dabigatran etexilate (ED50 = 4.4 +/- 2.2 mg/kg). (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.09.016
• 作为产物：
  描述：

  3-[[[2-[[(4-氰基苯基)氨基]甲基]-1-甲基-1H-苯并咪唑-5-基]羰基]吡啶-2-基氨基]丙酸乙酯 在 氨 、 sodium carbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， -10.0~60.0 ℃ 、1.07 kPa 条件下， 反应 24.5h， 生成 达比加群杂质38
  参考文献：
  名称：

  达比加群酯合成

  摘要：

  本发明涉及一种达比加群酯合成，其特征在于将取代苯氰在饱和的盐酸乙醇溶液中，在lewis酸催化下醇解，再与氨反应，然后将产物在碱存在下与氯甲酸正己酯反应得到达比加群酯，容易操作，绿色，收率高。

  公开号：

  CN108003138A

文献信息

• Process For The Preparation Of Benzimidazole Derivatives And Salts Thereof
  申请人：MSN Laboratories Limited

  公开号：US20150087842A1

  公开（公告）日：2015-03-26

  Provided are novel salts of benzimidazole derivatives, preferably salts of benzimidazole derivatives which are useful intermediates in the synthesis of pure 1-methyl-2-[N-[4-(N-n-hexyloxycarbonylamidino)phenyl]aminomethyl]benzimidazol-5-yl-carboxylicacid-N-(2-pyridyl)-N-(2-ethoxycarbonylethyl)amide and its salts.

  提供的是苯并咪唑衍生物的新型盐，最好是用于合成纯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)酰胺及其盐的苯并咪唑衍生物的盐。
• Process for the Synthesis of Dabigatran and Its Intermediates
  申请人：BIOPHORE INDIA PHARMACEUTICALS PVT. LTD.

  公开号：US20150246900A1

  公开（公告）日：2015-09-03

  The present invention describes an improved process for the preparation of Dabigatran Etexilate (Formula-I), a pharmaceutically acceptable salt for the treatment of thromboses, cardiovascular diseases etc. and intermediates involved in the synthesis.

  本发明描述了一种改进的制备达比加群酯（Formula-I）的过程，该化合物是治疗血栓、心血管疾病等的药用盐，同时涉及合成中间体。
• Design, synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing methyl ferulate
  作者：Xiao-Zhi Yang、Xiao-Juan Diao、Wen-Hui Yang、Feng Li、Guang-Wei He、Guo-Qing Gong、Yun-Gen Xu

  DOI：10.1016/j.bmcl.2013.01.126

  日期：2013.4

  A novel series of prodrugs containing dabigatran and methyl (E)-3-(4-hydroxy-2-methoxyphenyl)propenoate (methyl ferulate) were synthesized. All of them reveal the effect of thrombin-induced antiplatelet aggregation in vitro. In addition, in vivo experiment shows that one of the target compounds, X-2 (ED50 = 3.7 +/- 1.0 mu mol/kg) possesses a more potent activity for inhibiting venous thrombosis than that of dabigatran etexilate (ED50 = 7.8 +/- 1.5 mu mol/kg). (C) 2013 Elsevier Ltd. All rights reserved.
• Corrigendum to “Design, synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing methyl ferulate” [Bioorg. Med. Chem. Lett. 23 (2013) 2089–2092]
  作者：Xiao-Zhi Yang、Xiao-Juan Diao、Wen-Hui Yang、Feng Li、Guang-Wei He、Guo-Qing Gong、Yun-Gen Xu

  DOI：10.1016/j.bmcl.2013.07.065

  日期：2013.10
• PROCESS FOR THE PREPARATION OF BENZIMIDAZOLE DERIVATIVES AND SALTS THEREOF
  申请人：MSN Laboratories Limited

  公开号：EP2834224B1

  公开（公告）日：2018-06-06