(S)-3-[3-(N-Hydroxycarbamimidoyl)-phenyl]-2-(2,4,6-triisopropyl-benzenesulfonylamino)-propionic acid | 797040-05-2

• 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: (S)-3-[3-(N-Hydroxycarbamimidoyl)-phenyl]-2-(2,4,6-triisopropyl-benzenesulfonylamino)-propionic acid
• 英文别名: (2S)-3-[3-[(E)-N'-hydroxycarbamimidoyl]phenyl]-2-[[2,4,6-tri(propan-2-yl)phenyl]sulfonylamino]propanoic acid
• CAS: 797040-05-2
• 化学式: C₂₅H₃₅N₃O₅S
• 分子量: 489.636
• InChiKey: GYSITECXEZVWLC-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  151
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-3-[3-(N-Hydroxycarbamimidoyl)-phenyl]-2-(2,4,6-triisopropyl-benzenesulfonylamino)-propionic acid 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 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：

  L-3-氰基苯丙氨酸 在 盐酸羟胺 作用下， 以 乙醇 为溶剂， 生成 (S)-3-[3-(N-Hydroxycarbamimidoyl)-phenyl]-2-(2,4,6-triisopropyl-benzenesulfonylamino)-propionic acid
  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

• Secondary Amides of Sulfonylated 3-Amidinophenylalanine. New Potent and Selective Inhibitors of Matriptase
  作者：Torsten Steinmetzer、Andrea Schweinitz、Anne Stürzebecher、Daniel Dönnecke、Kerstin Uhland、Oliver Schuster、Peter Steinmetzer、Friedemann Müller、Rainer Friedrich、Manuel E. Than、Wolfram Bode、Jörg Stürzebecher

  DOI：10.1021/jm051272l

  日期：2006.7.1

  Matriptase is an epithelium-derived type II transmembrane serine protease and has been implicated in the activation of substrates such as pro-HGF/SF and pro-uPA, which are likely involved in tumor progression and metastasis. Through screening, we have identified bis-basic secondary amides of sulfonylated 3-amidinophenylalanine as matriptase inhibitors. X-ray analyses of analogues 8 and 31 in complex with matriptase revealed that these inhibitors occupy, in addition to part of the previously described S4-binding site, the cleft formed by the molecular surface and the unique 60 loop of matriptase. Therefore, optimization of the inhibitors included the incorporation of appropriate sulfonyl substituents that could improve binding of these inhibitors into both characteristic matriptase subsites. The most potent derivatives inhibit matriptase highly selective with K(i) values below 5 nM. Molecular modeling revealed that their improved affinity results from interaction with the S4 site of matriptase. Analogues 8 and 59 were studied in an orthotopic xenograft mouse model of prostate cancer. Compared to control, both inhibitors reduced tumor growth, as well as tumor dissemination.
• [DE] N-SULFONYLIERTE AMINOSÄUREDERIVATE UND IHRE VERWENDUNG ALS MATRIPTASE-INHIBITOREN<br/>[EN] N-SULPHONYLATED AMINO ACID DERIVATIVES AND USE THEREOF AS MATRIPTASE INHIBITORS<br/>[FR] DERIVES D'ACIDES AMINES N-SULFONYLES, PROCEDE DE PREPARATION DESDITS DERIVES ET LEUR UTILISATION
  申请人：CURACYTE CHEMISTRY GMBH

  公开号：WO2004101507A3

  公开（公告）日：2006-03-23
• Crystalline Modifications of N-Alpha-(2,4,6-Triisopropylphenylsulfonyl)-3-Hydroxyamidino- (L)- Phenylalanine 4-Ethoxycarbonylpiperazide And/Or Salts Thereof
  申请人：Grunenberg Alfons

  公开号：US20080058346A1

  公开（公告）日：2008-03-06

  The present invention relates to novel crystalline modifications of N-α-(2,4,6-triisopropylphenylsulfonyl)-3-hydroxyamidino-(L)-phenylalanine 4-ethoxycarbonylpiperazide and/or salts thereof, which can be used as pharmaceutical agents, and to pharmaceutical compositions and pharmaceutical uses comprising these novel crystalline modifications.
• 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.