tert-butyl N-[2-[1-[(2S)-2-[(3-aminophenyl)sulfonylamino]-3-(3-cyanophenyl)propanoyl]piperidin-4-yl]ethyl]carbamate | 901772-23-4

• 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: tert-butyl N-[2-[1-[(2S)-2-[(3-aminophenyl)sulfonylamino]-3-(3-cyanophenyl)propanoyl]piperidin-4-yl]ethyl]carbamate
• CAS: 901772-23-4
• 化学式: C₂₈H₃₇N₅O₅S
• 分子量: 555.698
• InChiKey: RQSWGFOSZCZVNT-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  163
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[2-[1-[(2S)-2-[(3-aminophenyl)sulfonylamino]-3-(3-cyanophenyl)propanoyl]piperidin-4-yl]ethyl]carbamate 在 N-甲基吗啉 、 盐酸羟胺 、 溶剂黄146 、 N,N-二异丙基乙胺 、 锌 、 氯甲酸异丁酯 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.17h， 生成 (2-{3-[(S)-2-[4-(2-tert-Butoxycarbonylamino-ethyl)-piperidin-1-yl]-1-(3-carbamimidoyl-benzyl)-2-oxo-ethylsulfamoyl]-phenylcarbamoyl}-ethyl)-carbamic acid benzyl ester
  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：

  4-(2-氨基乙基)吡啶 在 platinum(IV) oxide benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 溶剂黄146 、 N,N-二异丙基乙胺 、 锌 作用下， 以 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 112.83h， 生成 tert-butyl N-[2-[1-[(2S)-2-[(3-aminophenyl)sulfonylamino]-3-(3-cyanophenyl)propanoyl]piperidin-4-yl]ethyl]carbamate
  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

• 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.