tert-butyl (3-((4-bromophenyl)amino)-3-oxopropyl)carbamate

• 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 (3-((4-bromophenyl)amino)-3-oxopropyl)carbamate
• 英文别名: tert-butyl N-[3-(4-bromoanilino)-3-oxopropyl]carbamate
• 化学式: C₁₄H₁₉BrN₂O₃
• 分子量: 343.22
• InChiKey: PPKNHKGLYVDDDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (3-((4-bromophenyl)amino)-3-oxopropyl)carbamate 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以94%的产率得到3-amino-N-(4-bromophenyl)propanamide hydrochloride salt
  参考文献：
  名称：

  Discovery and Development of TMPRSS6 Inhibitors Modulating Hepcidin Levels in Human Hepatocytes

  摘要：

  Iron overload disorders are characterized by the body's inability to regulate iron absorption and its storage which can lead to organ failures. Accumulated evidence has revealed that hepcidin, the master regulator of iron homeostasis, is negatively modulated by TMPRSS6 (matriptase-2), a liver-specific type II transmembrane serine protease (TTSP). Here, we report that treatment with a pep-tidomimetic inhibitor affecting TMPRSS6 activity increases hepcidin production in hepatic cells. Moreover, similar effects were observed when using non-peptidic inhibitors obtained through optimization of hits from high-throughput screening. Using HepG2 cells and human primary hepato-cytes, we show that TMPRSS6 inhibitors block TMPRSS6- dependent hemojuvelin cleavage and increase HAMP expression and levels of secreted hepcidin.

  DOI：

  10.1016/j.chembiol.2019.09.004
• 作为产物：
  描述：

  Boc-beta-丙氨酸 、 4-溴苯胺 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以91%的产率得到tert-butyl (3-((4-bromophenyl)amino)-3-oxopropyl)carbamate
  参考文献：
  名称：

  Discovery and Development of TMPRSS6 Inhibitors Modulating Hepcidin Levels in Human Hepatocytes

  摘要：

  Iron overload disorders are characterized by the body's inability to regulate iron absorption and its storage which can lead to organ failures. Accumulated evidence has revealed that hepcidin, the master regulator of iron homeostasis, is negatively modulated by TMPRSS6 (matriptase-2), a liver-specific type II transmembrane serine protease (TTSP). Here, we report that treatment with a pep-tidomimetic inhibitor affecting TMPRSS6 activity increases hepcidin production in hepatic cells. Moreover, similar effects were observed when using non-peptidic inhibitors obtained through optimization of hits from high-throughput screening. Using HepG2 cells and human primary hepato-cytes, we show that TMPRSS6 inhibitors block TMPRSS6- dependent hemojuvelin cleavage and increase HAMP expression and levels of secreted hepcidin.

  DOI：

  10.1016/j.chembiol.2019.09.004

文献信息

• A PROCESS FOR RESOLVING RACEMIC MIXTURES AND A DIASTEREOISOMERIC COMPLEX OF A RESOLVING AGENT AND AN ENANTIOMER OF INTEREST
  申请人：ABIOGEN PHARMA S.p.A.

  公开号：EP1986996A2

  公开（公告）日：2008-11-05
• [EN] A PROCESS FOR RESOLVING RACEMIC MIXTURES AND A DIASTEREOISOMERIC COMPLEX OF A RESOLVING AGENT AND AN ENANTIOMER OF INTEREST<br/>[FR] PROCÉDÉ DE RÉSOLUTION DE MÉLANGES RACÉMIQUES ET COMPLEXE DIASTEREOMÈRE D'AGENT DE RÉSOLUTION ET D'ÉNANTIOMÈRE
  申请人：ABIOGEN PHARMA SPA

  公开号：WO2007088571A2

  公开（公告）日：2007-08-09

  [EN] A process for resolving a compound in racemic form comprising the following steps is described: a) reacting a compound in racemic form with a resolving agent, b) forming a diastereoisomeric complex of the resolving agent and an enantiomer of interest, c} separating the enantiomer of interest from the obtained diastereoisomer, wherein such a process is characterized in that said resolving agent is a compound of Formula (I). A diastereoisomeric complex between the resolving agent of Formula (I) and the enantiomer of interest is also described. The process according to the invention allows acid and basic racemic mixtures to be separated.
  [FR] L'invention concerne un procédé de résolution de composé sous forme racémique, qui consiste à: (a) effectuer la réaction du composé sous forme racémique avec un agent de résolution, (b) produire un complexe diastéréomère constitué de l'agent de résolution et d'un énantiomère, (c) séparer cet énantiomère du diastéréomère obtenu, ce procédé étant caractérisé par le fait que ledit agent de résolution est un composé représenté par la formule (I). L'invention concerne également un complexe diastéréomère constitué de l'agent de résolution représenté par la formule (I) et de l'énantiomère. Ce procédé permet de séparer des mélanges racémiques acides et basiques.
• Discovery and Development of TMPRSS6 Inhibitors Modulating Hepcidin Levels in Human Hepatocytes
  作者：François Béliveau、Aarti Tarkar、Sébastien P. Dion、Antoine Désilets、Mariana Gabriela Ghinet、Pierre-Luc Boudreault、Catherine St-Georges、Éric Marsault、Daniel Paone、Jon Collins、Colin H. Macphee、Nino Campobasso、Arthur Groy、Josh Cottom、Michael Ouellette、Andrew J. Pope、Richard Leduc

  DOI：10.1016/j.chembiol.2019.09.004

  日期：2019.11

  Iron overload disorders are characterized by the body's inability to regulate iron absorption and its storage which can lead to organ failures. Accumulated evidence has revealed that hepcidin, the master regulator of iron homeostasis, is negatively modulated by TMPRSS6 (matriptase-2), a liver-specific type II transmembrane serine protease (TTSP). Here, we report that treatment with a pep-tidomimetic inhibitor affecting TMPRSS6 activity increases hepcidin production in hepatic cells. Moreover, similar effects were observed when using non-peptidic inhibitors obtained through optimization of hits from high-throughput screening. Using HepG2 cells and human primary hepato-cytes, we show that TMPRSS6 inhibitors block TMPRSS6- dependent hemojuvelin cleavage and increase HAMP expression and levels of secreted hepcidin.