3-[3-(4-Methanesulfonyl-piperazin-1-yl)-3-oxo-2-(2,4,6-triisopropyl-benzenesulfonylamino)-propyl]-benzamidine

• 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: 3-[3-(4-Methanesulfonyl-piperazin-1-yl)-3-oxo-2-(2,4,6-triisopropyl-benzenesulfonylamino)-propyl]-benzamidine
• 英文别名: 3-[3-(4-methylsulfonylpiperazin-1-yl)-3-oxo-2-[[2,4,6-tri(propan-2-yl)phenyl]sulfonylamino]propyl]benzenecarboximidamide
• 化学式: C₃₀H₄₅N₅O₅S₂
• 分子量: 619.85
• InChiKey: OBICCCFHLMVXDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  171
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-氰基苯丙氨酸 在 吡啶 、 TEA 、 硫化氢 、 ammonium acetate 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 丙酮 为溶剂， 生成 3-[3-(4-Methanesulfonyl-piperazin-1-yl)-3-oxo-2-(2,4,6-triisopropyl-benzenesulfonylamino)-propyl]-benzamidine
  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

文献信息

• Synthesis and Structure−Activity Relationships of Potent Thrombin Inhibitors:  Piperazides of 3-Amidinophenylalanine
  作者：Jörg Stürzebecher、Dagmar Prasa、Jörg Hauptmann、Helmut Vieweg、Peter Wikström

  DOI：10.1021/jm960668h

  日期：1997.9.1

  Thrombin is the key enzyme in the blood coagulation system, and inhibitors of its proteolytic activity are of therapeutic interest since they are potential anticoagulants. The most potent inhibitor of the benzamidine type is N-alpha-[(2-naphthylsulfonyl)glycyl]-4-amidinophenylalanylpiperidide (NAPAP). However, NAPAP and other benzamidine derivatives do not show favorable pharmacological properties; above all, they have very low systemic bioavailability after oral administration. The goal of designing new compounds was to obtain potent inhibitors with improved pharmacokinetic properties. Piperazide derivatives of 3-amidinophenylalanine as the key building block were synthesized. The piperazine moiety opened the possibility to introduce quite different substituents on the second nitrogen using common synthetic procedures. Some of the newly synthesized compounds are potent inhibitors of thrombin and offer an approach to study structure-function relationships for inhibition of thrombin and related enzymes and for the improvement of their pharmacokinetic properties.
• 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.