3-[(S)-3-[4-(3-Amino-propionyl)-piperazin-1-yl]-2-(anthracene-2-sulfonylamino)-3-oxo-propyl]-benzamidine | 797040-10-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 3-[(S)-3-[4-(3-Amino-propionyl)-piperazin-1-yl]-2-(anthracene-2-sulfonylamino)-3-oxo-propyl]-benzamidine
• 英文别名: 3-[(2S)-3-[4-(3-aminopropanoyl)piperazin-1-yl]-2-(anthracen-2-ylsulfonylamino)-3-oxopropyl]benzenecarboximidamide
• CAS: 797040-10-9
• 化学式: C₃₁H₃₄N₆O₄S
• 分子量: 586.715
• InChiKey: BVJCIWUEZHDOJQ-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  171
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-[(S)-3-[4-(3-Amino-propionyl)-piperazin-1-yl]-2-(anthracene-2-sulfonylamino)-3-oxo-propyl]-benzamidine 、 1H-吡唑-1-甲脒盐酸盐 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-{(S)-2-(Anthracene-2-sulfonylamino)-3-[4-(3-guanidino-propionyl)-piperazin-1-yl]-3-oxo-propyl}-benzamidine
  参考文献：
  名称：

  Secondary Amides of Sulfonylated 3-Amidinophenylalanine. New Potent and Selective Inhibitors of Matriptase

  摘要：

  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.

  DOI：

  10.1021/jm051272l
• 作为产物：
  描述：

  tert-butyl (3-oxo-3-(piperazin-1-yl)propyl)carbamate 在 palladium on activated charcoal 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-[(S)-3-[4-(3-Amino-propionyl)-piperazin-1-yl]-2-(anthracene-2-sulfonylamino)-3-oxo-propyl]-benzamidine
  参考文献：
  名称：

  Secondary Amides of Sulfonylated 3-Amidinophenylalanine. New Potent and Selective Inhibitors of Matriptase

  摘要：

  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.

  DOI：

  10.1021/jm051272l

文献信息

• N-sulphonylated amino acid derivatives, method for the production and use thereof
  申请人：Sturzebecher Jorg

  公开号：US20070055065A1

  公开（公告）日：2007-03-08

  The present invention relates to N-sulfonylated amino acid derivatives, where an aryl radical is linked via the sulfonyl group N-terminally to the amino acid and a radical which comprises at least one imino group and at least one further basic group which represents an optionally modified amino, amidino or guanidino group is linked C-terminally via the carbonyl group. The invention likewise relates to processes for preparing these compounds and to their use, in particular as inhibitors of matriptase.

  本发明涉及N-磺酰化氨基酸衍生物，其中芳基基团通过磺酰基N-末端与氨基酸连接，而包含至少一个亚胺基团和至少一个其他碱性基团的基团则通过羰基基团C-末端连接。本发明还涉及制备这些化合物的方法以及它们的用途，特别是作为matriptase的抑制剂。
• N-SULPHONYLATED AMINO ACID DERIVATIVES, METHOD FOR THE PRODUCTION AND USE THEREOF
  申请人：Stürzebecher Jörg

  公开号：US20110002992A1

  公开（公告）日：2011-01-06

  The present invention relates to N-sulfonylated amino acid derivatives, where an aryl radical is linked via the sulfonyl group N-terminally to the amino acid and a radical which comprises at least one imino group and at least one further basic group which represents an optionally modified amino, amidino or guanidino group is linked C-terminally via the carbonyl group. The invention likewise relates to processes for preparing these compounds and to their use, in particular as inhibitors of matriptase.

  本发明涉及N-磺酰基氨基酸衍生物，其中芳基基团通过磺酰基N末端与氨基酸连接，而包含至少一个亚胺基团和至少一个进一步的碱性基团的基团，该基团表示为可选修饰的氨基，酰胺基或鸟氨酸基团，通过羰基基团C末端连接。本发明还涉及制备这些化合物的方法及其用途，特别是作为matriptase的抑制剂。
• US7772251B2
  申请人：——

  公开号：US7772251B2

  公开（公告）日：2010-08-10
• 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.