3-({2-[(4-{amino-[(E)-tert-butyloxycarbonylimino]methyl}phenylamino)methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}pyridin-2-yl-amino)propionic acid ethyl ester | 1415901-82-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 3-({2-[(4-{amino-[(E)-tert-butyloxycarbonylimino]methyl}phenylamino)methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}pyridin-2-yl-amino)propionic acid ethyl ester
• 英文别名: ethyl 3-[[1-methyl-2-[[4-[N'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]anilino]methyl]benzimidazole-5-carbonyl]-pyridin-2-ylamino]propanoate
• CAS: 1415901-82-4；1416446-44-0
• 化学式: C₃₂H₃₇N₇O₅
• 分子量: 599.69
• InChiKey: ZJSPHCKSLOQFQR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 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：

  3-({2-[(4-{amino-[(E)-tert-butyloxycarbonylimino]methyl}phenylamino)methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}pyridin-2-yl-amino)propionic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 4.0h， 以86%的产率得到3-[[1-methyl-2-[[4-[N'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]anilino]methyl]benzimidazole-5-carbonyl]-pyridin-2-ylamino]propanoic acid
  参考文献：
  名称：

  一种达比加群环状衍生物的制备方法

  摘要：

  本发明公开了一种如式VI所示的达比加群环状衍生物制备方法，该方法以达比加群乙酯为起始原料，经过脒基上保护基，酯基水解，羧基上保护基，最后缩合得到式VI所示达比加群环状衍生物。

  公开号：

  CN107739385A
• 作为产物：
  描述：

  叔-丁基氯甲酸酯 、 N-[[2-[[[4-(氨基亚氨基甲基)苯基]氨基]甲基]-1-甲基-1H-苯并咪唑-5-基]羰基]-n-(2-吡啶)-beta-丙氨酸乙酯盐酸盐 在 potassium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 3-({2-[(4-{amino-[(E)-tert-butyloxycarbonylimino]methyl}phenylamino)methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}pyridin-2-yl-amino)propionic acid ethyl ester
  参考文献：
  名称：

  Design, synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing methyl ferulate

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2013.01.126

文献信息

• Carbon-13 and carbon-14 labeled dabigatran etexilate and tritium labeled dabigatran
  作者：Bachir Latli、Ralf Kiesling、Stefan Aßfalg、Max Chevliakov、Matt Hrapchak、Scot Campbell、Nina Gonnella、Carl A. Busacca、Chris H. Senanayake

  DOI：10.1002/jlcr.3402

  日期：2016.12

  and carbon-14 labeled dabigatran etexilate, and tritium labeled dabigatran is described. The synthesis of carbon-13 dabigatran etexilate was accomplished in eight steps and in 6% overall yield starting from aniline-13 C6 . Ethyl bromoacetate-1-14 C was the reagent of choice in the synthesis of carbon-14 labeled dabigatran etexilate in six steps and 17% overall yield. Tritium labeled dabigatran was

  达比加群酯或 pradaxa 是一种新型口服抗凝剂，是一种可逆的、竞争性的、直接的凝血酶抑制剂。它用于预防心房颤动患者的中风以及在接受过髋关节或膝关节置换手术的成年人的静脉中形成血栓（深静脉血栓形成）。Pradaxa 是唯一一种新型口服抗凝剂，既证明优于华法林，又是一种用于罕见紧急情况的特定逆转剂。详细描述了碳 13 和碳 14 标记的达比加群酯和氚标记的达比加群的合成。从苯胺-13 C6 开始，碳-13 达比加群酯的合成分八步完成，总产率为 6%。1-14 C 溴乙酸乙酯是碳 14 标记的达比加群酯合成的首选试剂，分六步合成，总产率为 17%。氚标记的达比加群是在 Crabtree 催化条件下使用氚直接掺入或达比加群的二碘前体的氚脱卤来制备的。
• 一种达比加群环状衍生物的制备方法
  申请人：上海美悦生物科技发展有限公司

  公开号：CN107739385A

  公开（公告）日：2018-02-27

  本发明公开了一种如式VI所示的达比加群环状衍生物制备方法，该方法以达比加群乙酯为起始原料，经过脒基上保护基，酯基水解，羧基上保护基，最后缩合得到式VI所示达比加群环状衍生物。
• Synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing a cleavable moiety with anti-platelet activity
  作者：Xiao-Zhi Yang、Wen-Hui Yang、Yun-Gen Xu、Xiao-Juan Diao、Guang-Wei He、Guo-Qing Gong

  DOI：10.1016/j.ejmech.2012.09.016

  日期：2012.11

  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.
• 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
• 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.