2-(1-甲苯磺酰基-1H-咪唑-4-基)乙酸甲酯 | 497159-97-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(1-甲苯磺酰基-1H-咪唑-4-基)乙酸甲酯
• 英文名称: methyl {1-[(4-methylphenyl)sulfonyl]-1H-imidazol-4-yl}acetate
• 英文别名: [1-(toluene-4-sulfonyl)-1H-imidazol-4-yl]-acetic acid methyl ester；Methyl 2-(1-tosyl-1H-imidazol-4-YL)acetate；methyl 2-[1-(4-methylphenyl)sulfonylimidazol-4-yl]acetate
• CAS: 497159-97-4
• 化学式: C₁₃H₁₄N₂O₄S
• 分子量: 294.331
• InChiKey: NLNHCYPJGQABTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  86.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(1-甲苯磺酰基-1H-咪唑-4-基)乙酸甲酯 在 盐酸 、 sodium hydride 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.25h， 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：

  4-咪唑乙酸盐酸盐 在 盐酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.5h， 生成 2-(1-甲苯磺酰基-1H-咪唑-4-基)乙酸甲酯
  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

• [DE] IMIDAZOL-DERIVATE ALS TAFIA-INHIBITOREN<br/>[EN] IMIDAZOLE DERIVATIVES USED AS TAFIA INHIBITORS<br/>[FR] DERIVES D'IMIDAZOLE SERVANT D'INHIBITEURS DE TAFIA
  申请人：AVENTIS PHARMA GMBH

  公开号：WO2005105781A1

  公开（公告）日：2005-11-10

  Die Erfindung betrifft Verbindungen der Formel (I), die Inhibitoren von aktivierter Thrombin-aktivierbarer Fibrinolyse Inhibitor sind. Die Verbindungen der Formel I eignen sich zur Herstellung von Arzneimitteln zur Prophylaxe und Therapie von Erkrankungen, die mit Thrombosen, Embodien, Hyperkoagulabilität oder fibrotischen Veränderungen einhergehen.

  这项发明涉及公式（I）的连接物，其为激活的凝血酶激活纤溶抑制剂。公式I的连接物适用于制备用于预防和治疗与血栓形成、栓塞、高凝状态或纤维化变化相关的疾病的药物。
• Investigation of the Histamine H3 Receptor Binding Site. Design and Synthesis of Hybrid Agonists with a Lipophilic Side Chain
  作者：Makoto Ishikawa、Takashi Watanabe、Toshiaki Kudo、Fumikazu Yokoyama、Miki Yamauchi、Kazuhiko Kato、Nobukazu Kakui、Yasuo Sato

  DOI：10.1021/jm100643t

  日期：2010.9.9

  As a part of our search for novel histamine H3 receptor agonists, we designed and synthesized hybrid compounds in which the lipophilic (4′-alkylphenylthio)ethyl moiety of a novel H3 receptor agonist, 4-(2-(4′-tert-butylphenylthio)ethyl)-1H-imidazole (1), was incorporated into Nα-methylhistamine, immepip, and immethridine derivatives. These hybrid compounds were expected to interact concurrently with

  作为我们寻找新的组胺H3受体激动剂的一部分，我们设计并合成了杂化化合物，其中新型H3受体激动剂4-（2-（4'-叔丁基苯硫基）的亲脂性（4'-烷基苯硫基）乙基部分）乙基）-1 ħ -咪唑（1），被编入ñ α -甲基组胺，immepip，和immethridine衍生物。预期这些杂合化合物与H3受体中的组胺结合位点和假定的疏水区同时相互作用。其中，哌啶类和吡啶类衍生物表现出部分激动剂活性，而（S）-4-（1-（1 H-咪唑-4-基）-2-（4-（三氟甲基）苯硫基）乙基）哌啶（36）被确定为有效的H3激动剂。我们进行了计算对接研究，以检查激动剂的结合模式。结果表明，immepip与关键残基Asp114和Glu206的相互作用不同于组胺。36与这些残基的结合模式与immepip相似，并且36的亲脂性尾巴与受体的跨膜螺旋6中的疏水区具有额外的相互作用。这些结果表明36是研究受体激动剂相互作用和药物设计的有用工具。
• [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)。
• Synthesis and Evaluation of Imidazole Acetic Acid Inhibitors of Activated Thrombin-Activatable Fibrinolysis Inhibitor as Novel Antithrombotics
  作者：James C. Barrow、Philippe G. Nantermet、Shaun R. Stauffer、Phung L. Ngo、Melissa A. Steinbeiser、Shi-Shan Mao、Steven S. Carroll、Carolyn Bailey、Dennis Colussi、Michelle Bosserman、Christine Burlein、Jacquelynn J. Cook、Gary Sitko、Philip R. Tiller、Cynthia M. Miller-Stein、Mark Rose、Daniel R. McMasters、Joseph P. Vacca、Harold G. Selnick

  DOI：10.1021/jm034141y

  日期：2003.12.1

  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.