Nα-2,4,6-Triisopropylphenylsulfonyl-(L)-3-cyano-phenylalanine | 255374-80-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Nα-2,4,6-Triisopropylphenylsulfonyl-(L)-3-cyano-phenylalanine
• 英文别名: N-(2,4,6-triisopropylphenylsulfonyl)-3-cyano-(L)-phenylalanine；Tips-Phe(3-CN)-OH；L-Phenylalanine, 3-cyano-N-[[2,4,6-tris(1-methylethyl)phenyl]sulfonyl]-；(2S)-3-(3-cyanophenyl)-2-[[2,4,6-tri(propan-2-yl)phenyl]sulfonylamino]propanoic acid
• CAS: 255374-80-2
• 化学式: C₂₅H₃₂N₂O₄S
• 分子量: 456.606
• InChiKey: FEMOSTVRHHIDDH-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Nα-2,4,6-Triisopropylphenylsulfonyl-(L)-3-cyano-phenylalanine 在 盐酸羟胺 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成
  参考文献：
  名称：

  3-Amidinophenylalanine-based inhibitors of urokinase

  摘要：

  Synthesis and anti-uPA activity of a series of N alpha-triisopropyl-phenylsulfonyl-protecte 3-amidinophenylalanine amides are described. We have explored SAR around the C-terminal amide part for inhibition of uPA, plasmin and trypsin. Modification of the amide part has been found to affect potency but not selectivity. With a K-i of 0.41 mu M 2r-L is one of the most potent uPA inhibitors described so far. The X-ray crystal structure of 2r-L was solved in complex with trypsin, superimposed with uPA and the results suggest an unique binding mode of this inhibitor type. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00541-7
• 作为产物：
  描述：

  3-氰基苄基溴 在 盐酸 、 sodium hydroxide 、 acylase I from Aspergillus melleus 、 potassium iodide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 69.0h， 生成 Nα-2,4,6-Triisopropylphenylsulfonyl-(L)-3-cyano-phenylalanine
  参考文献：
  名称：

  [DE] HYDROXYAMIDIN- UND HYDROXYGUANIDIN-VERBINDUNGEN ALS UROKINASE-HEMMSTOFFE
  [EN] HYDROXYAMIDINE AND HYDROXYGUANIDINE COMPOUNDS AS UROKINASE INHIBITORS
  [FR] COMPOSES COMPORTANT DES GROUPES HYDROXYAMIDINE ET HYDROXYGUANIDINE UTILISES EN TANT QU'INHIBITEURS DE L'UROKINASE

  摘要：

  本发明涉及具有高生物利用度和口服可给性的新型抑制尿激酶-纤溶酶原激活物（uPA）的化合物，以及它们作为治疗性药物用于治疗与尿激酶或/和尿激酶受体相关的疾病，如肿瘤和转移等。该发明特别涉及含有羟基胺基或羟基胍基的化合物。其中，E代表来自公式（III）或公式（IV）的基团。

  公开号：

  WO2004103984A1

文献信息

• [EN] INHIBITORS OF GROWTH FACTOR ACTIVATION ENZYMES<br/>[FR] INHIBITEURS D'ENZYMES D'ACTIVATION DE FACTEUR DE CROISSANCE
  申请人：UNIV WASHINGTON

  公开号：WO2016144654A1

  公开（公告）日：2016-09-15

  The present invention generally relates to compounds that are useful for inhibiting one or more of hepatocyte growth factor activator, matriptase, hepsin, Factor Xa, or thrombin. The present invention also relates to various methods of using the inhibitor compounds including treating a malignancy, a pre-malignant condition, or cancer by administering an effective amount of the inhibitor to a subject in need thereof.

  本发明通常涉及对抑制肝细胞生长因子激活剂、麦曲丝蛋白、赫普星、Xa因子或凝血酶等的化合物有用的化合物。本发明还涉及使用抑制剂化合物的各种方法，包括通过向需要的受试者施用有效量的抑制剂来治疗恶性肿瘤、癌前病变或癌症。
• Hydroxyamidine and hydroxyguanidine compounds as urokinase inhibitors
  申请人：Wilex AG

  公开号：US07807681B2

  公开（公告）日：2010-10-05

  The present invention relates to novel compounds for inhibiting the urokinase plasminogen activator (uPA), which have high bioavailability and oral administerability, and also to the use thereof as therapeutic active compounds for the treatment of urokinase- or/and urokinase receptor-associated disorders such as, for example, tumors and metastasizing. The invention relates in particular to compounds containing hydroxyamidine or hydroxyguanidine groups.

  本发明涉及一种新型化合物，用于抑制尿激酶型纤溶酶原激活物（uPA），具有高生物利用度和口服给药性，并且用作治疗尿激酶或/和尿激酶受体相关疾病的治疗活性化合物，例如肿瘤和转移。本发明特别涉及含有羟基胍或羟基胍基团的化合物。
• Urokinase inhibitors
  申请人：Wilex AG

  公开号：US07745441B1

  公开（公告）日：2010-06-29

  New urokinase inhibitors having a triisopropylphenylsulfonyl residue as an Nα-substituent for 3-amidinophenylalanine are provided. The introduction of the triisopropylphenylsulfonyl residue greatly increases the affinity of the compounds to urokinase and, thereby, increases their inhibitory activity against urokinase. These urokinase inhibitors are useful in determining the role of urokinase and urokinase receptor in various diseases, particularly in tumor propagation and metastasis. Methods of treating tumors and a pharmaceutical composition are also provided.

  提供了一种具有三异丙基苯磺酰残基作为Nα-取代基的3-酰胺基苯丙氨酸的新型尿激酶抑制剂。引入三异丙基苯磺酰残基大大增加了化合物对尿激酶的亲和力，从而增加了它们对尿激酶的抑制活性。这些尿激酶抑制剂在确定尿激酶和尿激酶受体在各种疾病中的作用，特别是在肿瘤传播和转移中非常有用。还提供了治疗肿瘤的方法和制药组合物。
• Inhibitors of growth factor activation enzymes
  申请人：Janetka James W.

  公开号：US11130780B2

  公开（公告）日：2021-09-28

  The present invention generally relates to compounds that are useful for inhibiting one or more of hepatocyte growth factor activator, matriptase, hepsin, Factor Xa, or thrombin. The present invention also relates to various methods of using the inhibitor compounds including treating a malignancy, a pre-malignant condition, or cancer by administering an effective amount of the inhibitor to a subject in need thereof.

  本发明一般涉及可用于抑制一种或多种肝细胞生长因子激活剂、淀粉酶、肝素、Xa因子或凝血酶的化合物。 本发明还涉及使用抑制剂化合物的各种方法，包括通过向有需要的受试者施用有效量的抑制剂来治疗恶性肿瘤、恶性肿瘤前期病症或癌症。
• 3-Amidinophenylalanine-based inhibitors of urokinase
  作者：Jörg Stürzebecher、Helmut Vieweg、Torsten Steinmetzer、Andrea Schweinitz、Milton T. Stubbs、Martin Renatus、Peter Wikström

  DOI：10.1016/s0960-894x(99)00541-7

  日期：1999.11

  Synthesis and anti-uPA activity of a series of N alpha-triisopropyl-phenylsulfonyl-protecte 3-amidinophenylalanine amides are described. We have explored SAR around the C-terminal amide part for inhibition of uPA, plasmin and trypsin. Modification of the amide part has been found to affect potency but not selectivity. With a K-i of 0.41 mu M 2r-L is one of the most potent uPA inhibitors described so far. The X-ray crystal structure of 2r-L was solved in complex with trypsin, superimposed with uPA and the results suggest an unique binding mode of this inhibitor type. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.