3-(6-aminopyridin-3-yl)-2-(1H-imidazol-4-yl)propionic acid | 637776-45-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(6-aminopyridin-3-yl)-2-(1H-imidazol-4-yl)propionic acid
• 英文别名: 3-(6-aminopyridin-3-yl)-2-(1H-imidazol-5-yl)propanoic acid
• CAS: 637776-45-5；637776-46-6；497158-66-4
• 化学式: C₁₁H₁₂N₄O₂
• 分子量: 232.242
• InChiKey: IFHWJTOFROTZBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(6-aminopyridin-3-yl)-2-(1H-imidazol-4-yl)propionic acid 在 盐酸 、 sodium hydride 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 Ethyl 3-(6-aminopyridin-3-yl)-2-(1-methylimidazol-4-yl)propanoate
  参考文献：
  名称：

  Synthesis and Evaluation of Imidazole Acetic Acid Inhibitors of Activated Thrombin-Activatable Fibrinolysis Inhibitor as Novel Antithrombotics

  摘要：

  Thrombin-activatable fibrinolysis inhibitor (TAFI) is an important regulator of fibrinolysis, and inhibitors of this enzyme have potential use in antithrombotic and thrombolytic therapy. Appropriately substituted imidazole acetic acids such as 10j were found to be potent inhibitors of activated TAFI and selective versus the related carboxypeptidases CPA, CPN, and CPM but not CPB. Further, 10j accelerated clot lysis in vitro and was shown to be efficacious in a primate model of thrombosis.

  DOI：

  10.1021/jm034141y
• 作为产物：
  描述：

  2-(1H-咪唑-4-基)乙酸甲酯盐酸盐 在 盐酸 、 sodium hydride 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.75h， 生成 3-(6-aminopyridin-3-yl)-2-(1H-imidazol-4-yl)propionic acid
  参考文献：
  名称：

  Synthesis and Evaluation of Imidazole Acetic Acid Inhibitors of Activated Thrombin-Activatable Fibrinolysis Inhibitor as Novel Antithrombotics

  摘要：

  Thrombin-activatable fibrinolysis inhibitor (TAFI) is an important regulator of fibrinolysis, and inhibitors of this enzyme have potential use in antithrombotic and thrombolytic therapy. Appropriately substituted imidazole acetic acids such as 10j were found to be potent inhibitors of activated TAFI and selective versus the related carboxypeptidases CPA, CPN, and CPM but not CPB. Further, 10j accelerated clot lysis in vitro and was shown to be efficacious in a primate model of thrombosis.

  DOI：

  10.1021/jm034141y

文献信息

• IMIDAZOLE DERIVATIVES AS INHIBITORS OF TAFIA
  申请人：KALLUS Christopher

  公开号：US20080262028A1

  公开（公告）日：2008-10-23

  The present invention is directed to a compound of formula I: or any stereoisomeric form of the compound of the formula I or a mixture of these forms in any ratio or a physiologically acceptable salt of the compound of the formula I which inhibit the enzyme TAFIa (activated thrombin-activatable fibrinolysis inhibitor), and to a process for their preparation and to their use to treat described diseases where the substituents are as described in the specification.

  本发明涉及一种式I化合物： 或式I化合物的任何立体异构体形式，或这些形式的任何比例的混合物，或式I化合物的生理可接受盐，该化合物抑制酶TAFIa（活化的凝血酶可激活的纤维蛋白溶解抑制剂），以及涉及它们的制备方法及其用于治疗说明书中所述疾病的使用，其中取代基如说明书中所述。
• [EN] ANTICOAGULANT COMPOUNDS<br/>[FR] COMPOSES ANTICOAGULANTS
  申请人：MERCK & CO INC

  公开号：WO2003013526A1

  公开（公告）日：2003-02-20

  Compounds of the invention are useful in inhibiting carboxypeptidase U and associated thrombotic occlusions having the structure (I) and pharmaceutically acceptable salts thereof, wherein t is N or N(R2'), u is C(R3) or N(R2'), and v is C(R2), N or N(R2), provided that, 1) when t is N and u is C(R3), then v is N(R2); 2) when t is N and u is N(R2'), then v is C(R2), and 3) when t is N(R2') and u is C(R3), then v is N or N(R2).

  本发明的化合物在抑制羧肽酶U和相关的血栓闭塞性疾病中具有用途，其结构式为(I)及其药学上可接受的盐，其中t为N或N(R2')，u为C(R3)或N(R2')，v为C(R2)、N或N(R2)，但需满足以下条件：1）当t为N且u为C(R3)时，则v为N(R2)；2）当t为N且u为N(R2')时，则v为C(R2)；3）当t为N(R2')且u为C(R3)时，则v为N或N(R2)。
• Imidazole derivatives as inhibitors of TAFIa
  申请人：Sanofi-Aventis

  公开号：US08044208B2

  公开（公告）日：2011-10-25

  The present invention is directed to a compound of formula I: or any stereoisomeric form of the compound of the formula I or a mixture of these forms in any ratio or a physiologically acceptable salt of the compound of the formula I which inhibit the enzyme TAFIa (activated thrombin-activatable fibrinolysis inhibitor), and to a process for their preparation and to their use to treat described diseases where the substituents are as described in the specification.

  本发明涉及公式I的化合物，或公式I的任何立体异构体形式，或这些形式的任意比例混合物，或公式I的生理上可接受的盐，这些化合物抑制酶TAFIa（活化凝血酶活化的纤溶抑制剂），以及它们的制备方法和用于治疗所述疾病的用途，其中取代基如说明书所述。
• Imidazole acetic acid TAFIa inhibitors: SAR studies centered around the basic P 1 ′ group
  作者：Philippe G Nantermet、James C Barrow、Stacey R Lindsley、MaryBeth Young、Shi-Shan Mao、Steven Carroll、Carolyn Bailey、Michele Bosserman、Dennis Colussi、Daniel R McMasters、Joseph P Vacca、Harold G Selnick

  DOI：10.1016/j.bmcl.2004.02.033

  日期：2004.5

  Structural modifications of the aminopyridine P'(1), group of imidazole acetic acid based TAFla inhibitors led to the discovery of the aminocyclopentyl analog 28, a 1 nM TAFla inhibitor with CLT50 functional activity of 14 nM but without selectivity against CPB. While not as active, aminobutyl derivative 27 provided an improved 6.7-fold selectivity for TAFla versus CPB. (C) 2004 Elsevier Ltd. All rights reserved.
• IMIDAZOLDERIVATE ALS INHIBITOREN VON TAFI-A
  申请人：SANOFI

  公开号：EP1937673B1

  公开（公告）日：2015-10-21