2-[5'-aminomethyl-5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2'-dihydroxy-biphenyl-3-yl]-succinic acid | 488713-71-9

• 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: 2-[5'-aminomethyl-5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2'-dihydroxy-biphenyl-3-yl]-succinic acid
• 英文别名: 2-[3-[5-(aminomethyl)-2-hydroxyphenyl]-5-(6-carbamimidoyl-1H-benzimidazol-2-yl)-4-hydroxyphenyl]butanedioic acid
• CAS: 488713-71-9
• 化学式: C₂₅H₂₃N₅O₆
• 分子量: 489.488
• InChiKey: TYHGJVDXHMXVKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  220
• 氢给体数：
  8
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-[5'-aminomethyl-5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2'-dihydroxy-biphenyl-3-yl]-succinic acid 、 Potassium cyanate 在 乙腈 、 盐酸 作用下， 以 甲醇 、 盐酸 为溶剂， 反应 72.0h， 以to yield 4 mg (20%) of 2-[5-(5-Carbamimidoyl-1H-benzoimidazol-2-yl)-6,2′-dihydroxy-5′-uridomethyl-biphenyl-3-yl]-succinic acid) as the HCl salt的产率得到2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2'-dihydroxy-5'-ureidomethyl-biphenyl-3-yl]-succinic acid
  参考文献：
  名称：

  2-[5-(5-Carbamimidoyl-1H-heteroaryl)-6-hydroxybiphenyl-3-YL]-succinic acid derivatives as factor viia inhibitors

  摘要：

  本发明涉及新型因子VIIa、IXa、Xa、XIa的抑制剂，尤其是因子VIIa，包括这些抑制剂的制药组合物，以及使用这些抑制剂治疗或预防血栓栓塞性疾病的方法。本发明还揭示了制备这些抑制剂的过程。

  公开号：

  US20050176797A1
• 作为产物：
  描述：

  2-(4'-羟基苯基)丁烷-1,4-二酸 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 palladium dihydroxide 、 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 氯化亚砜 、 TEA 、 氢气 、 氧气 、 potassium acetate 、 sodium carbonate 、 N,N-二异丙基乙胺 、 magnesium chloride 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 生成 2-[5'-aminomethyl-5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6,2'-dihydroxy-biphenyl-3-yl]-succinic acid
  参考文献：
  名称：

  Factor VIIa inhibitors: Chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model

  摘要：

  Highly selective and potent factor VIIa-tissue factor (fVIIa.TF) complex inhibitors were generated through structure-based design. The pharmacokinetic properties of an optimized analog (9) were characterized in several preclinical species, demonstrating pharmacokinetic characteristics suitable for once-a-day dosing in humans. Analog 9 inhibited platelet and fibrin deposition in a dose-dependent manner after intravenous administration in a baboon thrombosis model, and a pharmacodynamic concentration-response model was developed to describe the platelet deposition data. Results for heparin and enoxaparin (Lovenox) in the baboon model are also presented.

  DOI：

  10.1016/j.bmcl.2005.12.059

文献信息

• 2- [5- (5-carbamimidoyl-1H-heteroaryl)-6-hydroxybiphenyl-3-yl]-succinic acid derivatives as factor viia inhibitors
  申请人：Axys Pharmaceuticals, Inc.

  公开号：US20030114457A1

  公开（公告）日：2003-06-19

  The present invention relates to novel inhibitors of Factors VIIa, IXa, Xa, XIa, in particular Factor VIIa, pharmaceutical compositions comprising these inhibitors, and methods for using these inhibitors for treating or preventing thromboembolic disorders. Processes for preparing these inhibitors are also disclosed.

  本发明涉及新型因子VIIa、IXa、Xa、XIa的抑制剂，特别是因子VIIa，包括这些抑制剂的药物组合物，以及利用这些抑制剂治疗或预防血栓栓塞性疾病的方法。还公开了制备这些抑制剂的方法。
• [EN] 2-[5-(5-CARBAMIMIDOYL-1 H -HETEROARYL)-6-HYDROXYBIPHENYL-3-YL]-SUCCINIC ACID DERIVATIVES AS FACTOR VIIA INHIBITORS<br/>[FR] DERIVES DE 2-[5-(5-CARBAMIMIDOYL-1 H -HETEROARYL)-6-HYDROXYBIPHENYL-3-YL]-ACIDE SUCCINIQUE UTILISES COMME INHIBITEURS DU FACTEUR VIIA
  申请人：AXYS PHARM INC

  公开号：WO2003006011A1

  公开（公告）日：2003-01-23

  The present invention relates to novel inhibitors of formula (I) of Factors VIIa, IXa, Xa, XIa, in particular Factor VIIa, pharmaceutical compositions comprising these inhibitors, and methods for using these inhibitors for treating or preventing thromboembolic disorders. Processes for preparing these inhibitors are also disclosed.

  本发明涉及公式（I）的新型抑制剂，该抑制剂可抑制VIIa，IXa，Xa，XIa等因子，特别是VIIa，以及包含这些抑制剂的制药组合物，以及使用这些抑制剂治疗或预防血栓栓塞性疾病的方法。还公开了制备这些抑制剂的方法。
• 2- 5-(5-CARBAMIMIDOYL-1 i H /i -HETEROARYL)-6-HYDROXYBIPHENYL-3-YL]-SUCCINIC ACID DERIVATIVES AS FACTOR VIIA INHIBITORS
  申请人：AXYS PHARMACEUTICALS, INC.

  公开号：EP1408963A1

  公开（公告）日：2004-04-21
• Factor VIIa inhibitors: Chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model
  作者：Wendy B. Young、Joyce Mordenti、Steven Torkelson、William D. Shrader、Aleksandr Kolesnikov、Roopa Rai、Liang Liu、Huiyong Hu、Ellen M. Leahy、Michael J. Green、Paul A. Sprengeler、Bradley A. Katz、Christine Yu、James W. Janc、Kyle C. Elrod、Ulla M. Marzec、Stephen R. Hanson

  DOI：10.1016/j.bmcl.2005.12.059

  日期：2006.4

  Highly selective and potent factor VIIa-tissue factor (fVIIa.TF) complex inhibitors were generated through structure-based design. The pharmacokinetic properties of an optimized analog (9) were characterized in several preclinical species, demonstrating pharmacokinetic characteristics suitable for once-a-day dosing in humans. Analog 9 inhibited platelet and fibrin deposition in a dose-dependent manner after intravenous administration in a baboon thrombosis model, and a pharmacodynamic concentration-response model was developed to describe the platelet deposition data. Results for heparin and enoxaparin (Lovenox) in the baboon model are also presented.
• 2-[5-(5-Carbamimidoyl-1H-heteroaryl)-6-hydroxybiphenyl-3-YL]-succinic acid derivatives as factor viia inhibitors
  申请人：Hu Huiyong

  公开号：US20050176797A1

  公开（公告）日：2005-08-11

  The present invention relates to novel inhibitors of Factors VIIa, IXa, Xa, XIa, in particular Factor VIIa, pharmaceutical compositions comprising these inhibitors, and methods for using these inhibitors for treating or preventing thromboembolic disorders. Processes for preparing these inhibitors are also disclosed.

  本发明涉及新型因子VIIa、IXa、Xa、XIa的抑制剂，尤其是因子VIIa，包括这些抑制剂的制药组合物，以及使用这些抑制剂治疗或预防血栓栓塞性疾病的方法。本发明还揭示了制备这些抑制剂的过程。