N'-(N-(tert-butoxycarbonyl)-N-(2-[(tert-butoxycarbonyl)amino]ethyl)-Gly-DL-phenylglycinyl)-5-nitro-2-furancarbohydrazide | 870154-27-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: N'-(N-(tert-butoxycarbonyl)-N-(2-[(tert-butoxycarbonyl)amino]ethyl)-Gly-DL-phenylglycinyl)-5-nitro-2-furancarbohydrazide
• 英文别名: tert-butyl N-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]-N-[2-[[2-[2-(5-nitrofuran-2-carbonyl)hydrazinyl]-2-oxo-1-phenylethyl]amino]-2-oxoethyl]carbamate
• CAS: 870154-27-1
• 化学式: C₂₇H₃₆N₆O₁₀
• 分子量: 604.617
• InChiKey: HTDIUWWUTYTWNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  43
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  214
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N'-(N-(tert-butoxycarbonyl)-N-(2-[(tert-butoxycarbonyl)amino]ethyl)-Gly-DL-phenylglycinyl)-5-nitro-2-furancarbohydrazide 在 盐酸 作用下， 以 甲醇 为溶剂， 以95%的产率得到N'-(2-(amino)ethyl-Gly-DL-phenylglycinyl)-5-nitro-2-furancarbohydrazide dihydrochloride
  参考文献：
  名称：

  Synthesis of 5-Nitro-2-furancarbohydrazides and Their cis-Diamminedichloroplatinum Complexes as Bitopic and Irreversible Human Thioredoxin Reductase Inhibitors

  摘要：

  The human selenoprotein thioredoxin reductase is involved in antioxidant defense and DNA synthesis. As increased thioredoxin reductase levels are associated with drug sensitivity to cisplatin and drug resistance in tumor cells, this enzyme represents a promising target for the development of cytostatic agents. To optimize the potential of the widely used cisplatin to inhibit the human thioredoxin reductase and therefore to overcome cisplatin resistance, we developed and synthesized four cis-diamminedichloroplatinum complexes of the lead 5-nitro-2-furan-carbohydrazide 8 selected from high-throughput screening. Detailed kinetics revealed that the isolated fragments, 5-nitro-2-furancarbohydrazide and cisplatin itself, bind with micromolar affinities at two different subsites of the human enzyme. By tethering both fragments four nitrofuran-based cis-diamminedichloroplatinum complexes 13a-c and 20 were synthesized and identified as biligand irreversible inhibitors of the human enzyme with nanomolar affinities. Studies with mutant enzymes clearly demonstrate the penultimate selenocysteine residue as the prime target of the synthesized cis-diamminedichloroplatinum complexes.

  DOI：

  10.1021/jm050256l
• 作为产物：
  描述：

  5-硝基-2-糠酸 在 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 96.0h， 生成 N'-(N-(tert-butoxycarbonyl)-N-(2-[(tert-butoxycarbonyl)amino]ethyl)-Gly-DL-phenylglycinyl)-5-nitro-2-furancarbohydrazide
  参考文献：
  名称：

  Synthesis of 5-Nitro-2-furancarbohydrazides and Their cis-Diamminedichloroplatinum Complexes as Bitopic and Irreversible Human Thioredoxin Reductase Inhibitors

  摘要：

  The human selenoprotein thioredoxin reductase is involved in antioxidant defense and DNA synthesis. As increased thioredoxin reductase levels are associated with drug sensitivity to cisplatin and drug resistance in tumor cells, this enzyme represents a promising target for the development of cytostatic agents. To optimize the potential of the widely used cisplatin to inhibit the human thioredoxin reductase and therefore to overcome cisplatin resistance, we developed and synthesized four cis-diamminedichloroplatinum complexes of the lead 5-nitro-2-furan-carbohydrazide 8 selected from high-throughput screening. Detailed kinetics revealed that the isolated fragments, 5-nitro-2-furancarbohydrazide and cisplatin itself, bind with micromolar affinities at two different subsites of the human enzyme. By tethering both fragments four nitrofuran-based cis-diamminedichloroplatinum complexes 13a-c and 20 were synthesized and identified as biligand irreversible inhibitors of the human enzyme with nanomolar affinities. Studies with mutant enzymes clearly demonstrate the penultimate selenocysteine residue as the prime target of the synthesized cis-diamminedichloroplatinum complexes.

  DOI：

  10.1021/jm050256l

文献信息

• Synthesis of 5-Nitro-2-furancarbohydrazides and Their <i>cis</i>-Diamminedichloroplatinum Complexes as Bitopic and Irreversible Human Thioredoxin Reductase Inhibitors
  作者：Régis Millet、Sabine Urig、Judit Jacob、Eberhard Amtmann、Jacques-Philippe Moulinoux、Stephan Gromer、Katja Becker、Elisabeth Davioud-Charvet

  DOI：10.1021/jm050256l

  日期：2005.11.1

  The human selenoprotein thioredoxin reductase is involved in antioxidant defense and DNA synthesis. As increased thioredoxin reductase levels are associated with drug sensitivity to cisplatin and drug resistance in tumor cells, this enzyme represents a promising target for the development of cytostatic agents. To optimize the potential of the widely used cisplatin to inhibit the human thioredoxin reductase and therefore to overcome cisplatin resistance, we developed and synthesized four cis-diamminedichloroplatinum complexes of the lead 5-nitro-2-furan-carbohydrazide 8 selected from high-throughput screening. Detailed kinetics revealed that the isolated fragments, 5-nitro-2-furancarbohydrazide and cisplatin itself, bind with micromolar affinities at two different subsites of the human enzyme. By tethering both fragments four nitrofuran-based cis-diamminedichloroplatinum complexes 13a-c and 20 were synthesized and identified as biligand irreversible inhibitors of the human enzyme with nanomolar affinities. Studies with mutant enzymes clearly demonstrate the penultimate selenocysteine residue as the prime target of the synthesized cis-diamminedichloroplatinum complexes.