Nec-1s

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: Nec-1s
• 英文别名: necrostatin-1s；5-((7-Chloro-1H-indol-3-yl)methyl)-3-methylimidazolidine-2,4-dione；Necrostatin 2 racemate；5-[(7-chloro-1H-indol-3-yl)methyl]-3-methylimidazolidine-2,4-dione
• 化学式: C₁₃H₁₂ClN₃O₂
• 分子量: 277.71
• InChiKey: WIKGAEMMNQTUGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  65.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  7-氯-1H-吲哚-3-苯甲醛 在 哌啶 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 28.0h， 生成 Nec-1s
  参考文献：
  名称：

  Structure–activity relationship study of novel necroptosis inhibitors

  摘要：

  Necroptosis is a regulated caspase-independent cell death mechanism that results in morphological features resembling necrosis. It can be induced in a FADD-deficient variant of human Jurkat T cells treated with TNF-alpha. 5-(1H-Indol-3-ylmethyl)-2-thiohydantoins and 5-(1H-indol-3-ylmethyl)hydantoins were found to be potent necroptosis inhibitors (called necrostatins). A SAR study revealed that several positions of the indole were intolerant of substitution, while small substituents at the 7-position resulted in increased inhibitory activity. The hydantoin ring was also quite sensitive to structural modifications. A representative member of this compound class demonstrated moderate pharmacokinetic characteristics and readily entered the central nervous system upon intravenous administration. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.077

文献信息

• [EN] AMINOTRIAZOLOPYRIDINES AS KINASE INHIBITORS<br/>[FR] AMINOTRIAZOLOPYRIDINES UTILISÉES EN TANT QU'INHIBITEURS DE KINASE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2018148626A1

  公开（公告）日：2018-08-16

  Compounds having formula (I) (IX), and enantiomers, and diastereomers, stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, are useful as kinase modulators, including RIPK1 modulation. All the variables are as defined herein: (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX).

  具有化学式（I）（IX）的化合物，以及其对映体、非对映体、立体异构体、药学上可接受的盐和前药，可用作激酶调节剂，包括RIPK1调节。所有变量的定义如下：（I）、（II）、（III）、（IV）、（V）、（VI）、（VII）、（VIII）、（IX）。
• [EN] DEUTERATED HETEROCYCLIC INHIBITORS OF NECROPTOSIS<br/>[FR] INHIBITEURS HÉTÉROCYCLIQUES DEUTÉRÉS DE NÉCROPTOSE
  申请人：HARVARD COLLEGE

  公开号：WO2014152182A1

  公开（公告）日：2014-09-25

  The present invention relates to isolated deuterated compounds (e.g., compounds described by Formula (I) and pharmaceutically acceptable salts thereof. The present invention also relates to isotopically enriched compositions that include compounds according to Formula (I) and pharmaceutically acceptable salts thereof. The invention also features pharmaceutical compositions that include these compounds and their use in therapy for treating conditions in which necroptosis is likely to play a substantial role, or those conditions in which RIP1 and/or RIP3 protein is a contributing factor, (structure shown)

  本发明涉及孤立的氘化合物（例如，由式（I）描述的化合物及其药用盐。本发明还涉及包括符合式（I）和其药用盐的同位素富集组合物。该发明还涉及包括这些化合物的药物组合物及其在治疗可能大量发挥坏死激发作用的疾病或其中RIP1和/或RIP3蛋白是促发因素的疾病中的使用。
• IDENTIFICATION AND TREATMENT OF VULNERABLE PLAQUES
  申请人：OTTAWA HEART INSTITUTE RESEARCH CORPORATION

  公开号：US20160324992A1

  公开（公告）日：2016-11-10

  A method of detecting an atherosclerotic plaque vulnerable to rupture in a subject comprises providing to the subject a labelled necrostatin or a derivative thereof, and visualizing the label, wherein a localization of the label in a plaque indicates the plaque is vulnerable to rupture. A method of detecting and treating an atherosclerotic plaque vulnerable to rupture comprises providing to the subject a labelled necrostatin or a derivative thereof, visualizing the label, wherein a localization of the label in a plaque indicates the plaque is vulnerable to rupture; and providing a necroptosis inhibitor or derivative thereof to the subject when the visualizing indicates that the plaque is vulnerable to rupture. The necroptosis inhibitor may comprise a necrostatin, such as Nec-1. The label may be a radiolabel such as 123 I. By visualizing plaques vulnerable to rupture, atherosclerotic plaques may be identified and treated in advance of rupture.

  在一个主体中检测易破裂的动脉粥样硬化斑块的方法包括向主体提供标记的坏死激酶抑制剂或其衍生物，并可视化标记，标记在斑块中的定位表明该斑块易破裂。检测和治疗易破裂的动脉粥样硬化斑块的方法包括向主体提供标记的坏死激酶抑制剂或其衍生物，可视化标记，标记在斑块中的定位表明该斑块易破裂；当可视化表明斑块易破裂时，向主体提供坏死激酶抑制剂或其衍生物。坏死激酶抑制剂可能包括坏死激酶，如Nec-1。标记可以是放射性标记，如123I。通过可视化易破裂的斑块，可以提前识别和治疗动脉粥样硬化斑块。
• Inhibitors of cellular necrosis
  申请人：Cuny Gregory D.

  公开号：US20110144169A1

  公开（公告）日：2011-06-16

  The present invention relates to compounds and pharmaceutical preparations and their use in therapy for preventing or treating trauma, ischemia, stroke and degenerative diseases associated with cell death. Methods and compositions of the invention are particularly useful for treating neurological disorders associated with cellular necrosis.

  本发明涉及化合物及其制药制剂，以及它们在治疗预防或治疗创伤、缺血、中风和与细胞死亡相关的退行性疾病中的应用。本发明的方法和组合物特别适用于治疗与细胞坏死相关的神经系统疾病。
• Compounds, Screens, and Methods of Treatment
  申请人：Yuan Junying

  公开号：US20100190836A1

  公开（公告）日：2010-07-29

  The present invention features compounds, pharmaceutical compositions, and methods for treating trauma, ischemia, stroke, degenerative diseases associated with cellular necrosis, and other conditions. Screening assays for identifying compounds useful for treating these conditions are also described.

  本发明涉及化合物、药物组合物和治疗创伤、缺血、中风、与细胞坏死相关的退行性疾病以及其他疾病的方法。还描述了用于识别治疗这些疾病的化合物的筛选测定方法。