3-({2-[(4-{amino-[(E)-pentyloxycarbonylimino]methyl}-phenylamino)methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}pyridin-2-yl-amino)propionic acid | 1416446-60-0

• 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)-pentyloxycarbonylimino]methyl}-phenylamino)methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}pyridin-2-yl-amino)propionic acid
• 英文别名: 3-[[1-methyl-2-[[4-(N-pentoxycarbonylcarbamimidoyl)anilino]methyl]benzimidazole-5-carbonyl]-pyridin-2-ylamino]propanoic acid
• CAS: 1416446-60-0
• 化学式: C₃₁H₃₅N₇O₅
• 分子量: 585.663
• InChiKey: YFAFXUFWKLTODU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  43
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  165
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-({2-[(4-{amino-[(E)-pentyloxycarbonylimino]methyl}-phenylamino)methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}pyridin-2-yl-amino)propionic acid 、 (3,5,6-三甲基吡嗪-2-基)甲醇 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.5h， 以63.9%的产率得到(3,5,6-trimethylpyrazin-2-yl)methyl 3-[[1-methyl-2-[[4-(N-pentoxycarbonylcarbamimidoyl)anilino]methyl]benzimidazole-5-carbonyl]-pyridin-2-ylamino]propanoate
  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：

  氯甲酸正戊酯 在 potassium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 10.33h， 生成 3-({2-[(4-{amino-[(E)-pentyloxycarbonylimino]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

文献信息

• 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