(S,E)-tert-butyl (8-((1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)amino)-2-methyl-8-oxooct-5-en-4-yl)carbamate | 1287791-37-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (S,E)-tert-butyl (8-((1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)amino)-2-methyl-8-oxooct-5-en-4-yl)carbamate
• 英文别名: JP4-039；tert-butyl N-[(E,4S)-8-[(1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)amino]-2-methyl-8-oxooct-5-en-4-yl]carbamate
• CAS: 1287791-37-0
• 化学式: C₂₃H₄₃N₃O₄
• 分子量: 425.612
• InChiKey: RMCJGDMSSLVWTE-SXSDINLZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  90.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S,E)-tert-butyl (8-((1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)amino)-2-methyl-8-oxooct-5-en-4-yl)carbamate 在 copper(II) acetate monohydrate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 22.5h， 生成 (S,E)-5,5-difluoro-3-(3-((8-((1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)amino)-2-methyl-8-oxooct-5-en-4-yl)amino)-3-oxopropyl)-7-phenyl-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide
  参考文献：
  名称：

  Synthesis of analogs of the radiation mitigator JP4-039 and visualization of BODIPY derivatives in mitochondria

  摘要：

  JP4-039 是一系列硝基氧化物共轭物的先导结构，能够在线粒体中积累并清除活性氧（ROS）。为了探索结构-活性关系（SAR），我们制备了具有可变亚硝基的新类似物。此外，还合成了荧光团标记的类似物，为线粒体中的可视化提供了机会。所有类似物都在 32Dcl3 细胞中进行了辐射防护和辐射诱变效应测试。

  DOI：

  10.1039/c3ob40489g
• 作为产物：
  描述：

  N-叔丁氧羰基-L-亮氨醇 在 sodium hydride 、 维生素 C 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 、 mineral oil 为溶剂， 反应 0.58h， 生成 (S,E)-tert-butyl (8-((1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)amino)-2-methyl-8-oxooct-5-en-4-yl)carbamate
  参考文献：
  名称：

  由N -Boc-1-亮氨酸两步合成生物保护剂JP4-039

  摘要：

  从N- Boc- 1-亮氨酸描述了生物保护剂JP4-039的快速合成，总产率为50％。合成过程涉及使用α，β-不饱和重氮酮作为关键中间体，然后在4-氨基-TEMPO（4-AT）存在下进行光化学Wolff重排。

  DOI：

  10.1016/j.tet.2013.10.059

文献信息

• TARGETED NITROXIDE AGENTS
  申请人：Wipf Peter

  公开号：US20100035869A1

  公开（公告）日：2010-02-11

  Provided herein are compositions and related methods useful for free radical scavenging, with particular selectivity for mitochondria. The compounds comprise a nitroxide-containing group attached to a mitochondria-targeting group. The compounds can be cross-linked into dimers without loss of activity. Also provided herein are methods, for preventing, mitigating and treating damage caused by radiation. The method comprises delivering a compound, as described herein, to a patient in an amount and dosage regimen effective to prevent, mitigate or treat damage caused by radiation.

  本文提供了一种对自由基清除有用的组合物和相关方法，具有特定选择性作用于线粒体。这些化合物包括一个连接到线粒体靶向基团的亚硝基含有基团。这些化合物可以交联成二聚体而不丧失活性。本文还提供了一种用于预防、缓解和治疗辐射引起的损伤的方法。该方法包括向患者输送一种如本文所述的化合物，以有效地预防、缓解或治疗辐射引起的损伤。
• INTRAESOPHAGEAL ADMINISTRATION OF TARGETED NITROXIDE AGENTS FOR PROTECTION AGAINST IONIZING IRRADIATION-INDUCED ESOPHAGITIS
  申请人：University of Pittsburgh - Of the Commonwealth System of Higher Education

  公开号：US20190210969A1

  公开（公告）日：2019-07-11

  Provided herein are compositions and related methods useful for prevention or mitigation of ionizing radiation-induced esophagitis. The compositions comprise compounds comprising a nitroxide-containing group attached to a mitochondria-targeting group. The compounds can be cross-linked into dimers without loss of activity. The method comprises delivering a compound, as described herein, to a patient in an amount and dosage regimen effective to prevent or mitigate esophageal damage caused by radiation.

  本文提供了一种用于预防或缓解电离辐射诱导的食管炎的组合物和相关方法。这些组合物包括含有与线粒体靶向基团相连的亚硝基含有基团的化合物。这些化合物可以交联成二聚体而不丧失活性。该方法包括向患者输送本文所述的化合物，以有效预防或缓解由辐射引起的食道损伤。
• Compounds for the treatment of pathologies associated with aging and degenerative disorders
  申请人：University of Pittsburgh—of the Commonwealth System of Higher Education

  公开号：US10751273B2

  公开（公告）日：2020-08-25

  The present invention relates to methods of inhibiting one or more signs of aging and/or degenerative disorder in a subject in need of such treatment, which comprise administering, to the subject, an effective amount of one or more of the compounds as set forth herein. “Inhibiting a sign of aging or degenerative disorder” means reducing the risk of occurrence, delaying the onset, slowing the progression, and/or reducing the severity and/or manifestation, of a sign of aging or degenerative disorder, and includes, but is not limited to, preventing the occurrence, development or progression of a sign of aging or degenerative disorder.

  本发明涉及在需要治疗的受试者中抑制一种或多种衰老和/或退行性失调迹象的方法，其中包括向受试者施用有效量的一种或多种本文所述化合物。"抑制衰老或退行性病变的征兆 "是指降低衰老或退行性病变征兆的发生风险、延迟发病、减缓进展和/或降低严重程度和/或表现，并包括但不限于预防衰老或退行性病变征兆的发生、发展或进展。
• Large-Scale Asymmetric Synthesis of the Bioprotective Agent JP4-039 and Analogs
  作者：Marie-Céline Frantz、Joshua G. Pierce、Joan M. Pierce、Li Kangying、Wan Qingwei、Matthew Johnson、Peter Wipf

  DOI：10.1021/ol200567p

  日期：2011.5.6

  JP4-039 is a novel nitroxide conjugate capable of crossing lipid bilayer membranes and scavenging reactive oxygen species (ROS). An efficient and scalable one-pot hydrozirconation-transmetalation-imine addition methodology has been developed for its asymmetric preparation. Furthermore, this versatile methodology allows for the synthesis of cyclopropyl and fluorinated analogs of the parent lead structure.
• US8288551B2
  申请人：——

  公开号：US8288551B2

  公开（公告）日：2012-10-16