tert-butyl 4-(6-chloro-3-nitropyridin-2-yl)piperazine-1-carboxylate | 474330-06-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(6-chloro-3-nitropyridin-2-yl)piperazine-1-carboxylate
• CAS: 474330-06-8
• 化学式: C₁₄H₁₉ClN₄O₄
• 分子量: 342.782
• InChiKey: ZTZUFALUKUFVNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  91.5
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(6-chloro-3-nitropyridin-2-yl)piperazine-1-carboxylate 在 铁粉 、 氯化铵 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 tert-butyl 4-{6-chloro-3-[2-(dimethylamino)acetamido]pyridin-2-yl}piperazine-1-carboxylate
  参考文献：
  名称：

  NOVEL 5H-PYRROLO[2,3-D]PYRIMIDIN-6(7H)-ONE DERIVATIVE

  摘要：

  公开号：

  EP3459953B1
• 作为产物：
  描述：

  2,6-二氯-3-硝基吡啶 、 N-Boc-哌嗪 在 乙酸乙酯 、 正己烷 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以to yield 4-(6-chloro-3-nitro-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester as a yellow solid, 0.87 g, 2.54 mmol, 49%的产率得到tert-butyl 4-(6-chloro-3-nitropyridin-2-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  Inhibitors of bace

  摘要：

  本发明涉及天冬氨酸蛋白酶的抑制剂，特别是BACE。本发明还涉及其组成物和方法，用于抑制哺乳动物中BACE的活性，并用于治疗阿尔茨海默病和其他BACE介导的疾病。

  公开号：

  US20030095958A1

文献信息

• Insights into the interaction of negative allosteric modulators with the metabotropic glutamate receptor 5: Discovery and computational modeling of a new series of ligands with nanomolar affinity
  作者：Andrew Anighoro、Davide Graziani、Ilaria Bettinelli、Antonio Cilia、Carlo De Toma、Matteo Longhi、Fabio Mangiarotti、Sergio Menegon、Lorenza Pirona、Elena Poggesi、Carlo Riva、Giulio Rastelli

  DOI：10.1016/j.bmc.2015.05.008

  日期：2015.7

  Metabotropic glutamate receptor 5 (mGlu(5)) is a biological target implicated in major neurological and psychiatric disorders. In the present study, we have investigated structural determinants of the interaction of negative allosteric modulators (NAMs) with the seven-transmembrane (7TM) domain of mGlu(5). A homology model of the 7TM receptor domain built on the crystal structure of the mGlu(1) template was obtained, and the binding modes of known NAMs, namely MPEP and fenobam, were investigated by docking and molecular dynamics simulations. The results were validated by comparison with mutagenesis data available in the literature for these two ligands, and subsequently corroborated by the recently described mGlu(5) crystal structure. Moreover, a new series of NAMs was synthesized and tested, providing compounds with nanomolar affinity. Several structural modifications were sequentially introduced with the aim of identifying structural features important for receptor binding. The synthesized NAMs were docked in the validated homology model and binding modes were used to interpret and discuss structure-activity relationships within this new series of compounds. Finally, the models of the interaction of NAMs with mGlu(5) were extended to include important non-aryl alkyne mGlu(5) NAMs taken from the literature. Overall, the results provide useful insights into the molecular interaction of negative allosteric modulators with mGlu(5) and may facilitate the design of new modulators for this class of receptors. (C) 2015 Elsevier Ltd. All rights reserved.
• INHIBITORS OF BACE
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP1389194A2

  公开（公告）日：2004-02-18
• [EN] INHIBITORS OF BACE<br/>[FR] INHIBITEURS DE BACE
  申请人：VERTEX PHARMA

  公开号：WO2002088101A2

  公开（公告）日：2002-11-07

  The present invention relates to inhibitors of aspartic proteinases, particularly, BACE. The present invention also relates to compositions thereof and methods therewith for inhibiting BACE activity in a mammal, and for treating Alzheimer's Disease and other BACE-mediated diseases.
• Inhibitors of bace
  申请人：——

  公开号：US20030095958A1

  公开（公告）日：2003-05-22

  The present invention relates to inhibitors of aspartic proteinases, particularly, BACE. The present invention also relates to compositions thereof and methods therewith for inhibiting BACE activity in a mammal, and for treating Alzheimer's Disease and other BACE-mediated diseases.

  本发明涉及天冬氨酸蛋白酶抑制剂，特别是BACE。本发明还涉及其组合物和方法，用于在哺乳动物中抑制BACE活性，并用于治疗阿尔茨海默病和其他BACE介导的疾病。
• NOVEL 5H-PYRROLO[2,3-D]PYRIMIDIN-6(7H)-ONE DERIVATIVE
  申请人：Taiho Pharmaceutical Co., Ltd.

  公开号：EP3459953B1

  公开（公告）日：2021-06-30