1-甲基-3-（1-甲基吲哚-3-基）-4-（戊氨基）吡咯-2,5-二酮 | 861891-50-1

• 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
• 中文名称: 1-甲基-3-（1-甲基吲哚-3-基）-4-（戊氨基）吡咯-2,5-二酮
• 中文别名: 2-(1H-吲哚-3-基)-3-戊基氨基马来酰亚胺；IM54（2-（1H-吲哚-3-基）-3-戊基氨基马来酰亚胺）
• 英文名称: IM-54
• 英文别名: 1-methyl-3-(1-methyl-1H-indol-3-yl)-4-(pentylamino)-1H-pyrrole-2,5-dione；1-methyl-3-(1-methylindol-3-yl)-4-(pentylamino)pyrrole-2,5-dione
• CAS: 861891-50-1
• 化学式: C₁₉H₂₃N₃O₂
• 分子量: 325.411
• InChiKey: SGLOMINNEBLJFF-UHFFFAOYSA-N

物化性质

• 沸点：
  511.5±50.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：可溶，5mg/mL（澄清溶液）

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  54.3
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  6.1

制备方法与用途

生物活性

IM-54 是一种选择性的氧化应激诱导的坏死（necrosis）抑制剂。它对 H₂O₂ 诱导的坏死有强烈的抑制作用，并且是一种潜在的心脏保护剂，也可作为研究细胞死亡分子机制的生物工具。

体外研究

IM-54 仅特异性地抑制氧化应激诱导的坏死，而不影响各种抗肿瘤药物或 Fas配体以及焦亡（necroptosis）引起的凋亡。IM-54 对 HL-60 细胞在 H₂O₂ 处理下的 H₂O₂ 诱导坏死表现出强烈的抑制作用，其 IC₅₀ 值为 0.25 μM。

反应信息

• 作为反应物：
  描述：

  1-甲基-3-（1-甲基吲哚-3-基）-4-（戊氨基）吡咯-2,5-二酮 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 以88%的产率得到5-hydroxy-1-methyl-3-(1-methyl-1H-indol-3-yl)-4-(pentylamino)-1H-pyrrole-2(5H)-one
  参考文献：
  名称：

  Structure–Activity Relationship Study of 3-Amino-2-indolyllactam Derivatives: Development of Inhibitors of Oxidative Stress-Induced Necrosis

  摘要：

  我们之前报道的选择性氧化应激诱导坏死抑制剂2-(1H-吲哚-3-基)-3-戊胺基马来酰亚胺（IM-54）的C-4羰基区域选择性还原，得到了活性更强的3-氨基-2-吲哚基内酰胺（IL-1）。为了研究IL衍生物的构效关系，我们开发了新的合成路线，可以在后期灵活引入多种取代基。合成的IL衍生物进行了抑制过氧化氢诱导细胞坏死活性的评估。其中，IL-12在所检测的IL和吲哚基马来酰亚胺（IM）衍生物中显示出最强的活性（IC50=49 nM）。

  DOI：

  10.1248/cpb.c16-00259
• 作为产物：
  描述：

  3-bromo-4-(1H-indol-3-yl)-1-methyl-1H-pyrrole-2,5-dione 在 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-甲基-3-（1-甲基吲哚-3-基）-4-（戊氨基）吡咯-2,5-二酮
  参考文献：
  名称：

  Inhibition of hydrogen peroxide-induced necrotic cell death with 3-amino-2-indolylmaleimide derivatives

  摘要：

  Novel analogs of indolylmaleimide derivatives (IM derivatives) were synthesized and tested for cell death-inhibitory activity. 2-(1H-Indol-3-yl)-3-pentylamino-maleimide IM-54 was the most effective cell death inhibitor among the compounds tested. IM-54 inhibited necrotic cell death induced by H2O2, but not apoptotic cell death induced by etoposide. These results indicated that this novel cell death inhibitor is distinct from the well-known caspase inhibitor, Z-VAD, which can block apoptotic cell death, but not necrotic cell death. IM-54 is expected to be a powerful bioprobe for clarifying the unique signaling pathway of necrotic cell death. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.04.016

文献信息

• Methods and compositions for restoring homeostatic capacity of a subject
  申请人：Palo Alto Investors

  公开号：US10835134B2

  公开（公告）日：2020-11-17

  Methods of restoring homeostatic capacity of a subject are provided. Aspects of the invention further include compositions, systems and devices for practicing the methods. The methods and compositions described herein find use in a variety of applications. Aspects of certain embodiments of the methods include modulating a subject's autonomic nervous system in a manner sufficient to restore the homeostatic capacity of the subject. Aspects of other embodiments of the invention include administering to the subject an amount of an apoptosis modulator effective to at least partially restore homeostatic function of the neuroendocrine system of the subject.

  本发明提供了恢复受试者体内平衡能力的方法。本发明的各个方面还包括用于实施这些方法的组合物、系统和设备。本文所述的方法和组合物可用于多种应用。本发明方法的某些实施方案包括以足以恢复受试者平衡能力的方式调节受试者的自律神经系统。本发明其他实施方案的方面包括向受试者施用一定量的细胞凋亡调节剂，其有效量至少可部分恢复受试者神经内分泌系统的平衡功能。
• Methods and Compositions for Restoring Homeostatic Capacity of a Subject
  申请人：Palo Alto Investors

  公开号：US20150359888A1

  公开（公告）日：2015-12-17

  Methods of restoring homeostatic capacity of a subject are provided. Aspects of the invention further include compositions, systems and devices for practicing the methods. The methods and compositions described herein find use in a variety of applications.
• Inhibition of hydrogen peroxide-induced necrotic cell death with 3-amino-2-indolylmaleimide derivatives
  作者：Kosuke Dodo、Miho Katoh、Tadashi Shimizu、Masahiro Takahashi、Mikiko Sodeoka

  DOI：10.1016/j.bmcl.2005.04.016

  日期：2005.6

  Novel analogs of indolylmaleimide derivatives (IM derivatives) were synthesized and tested for cell death-inhibitory activity. 2-(1H-Indol-3-yl)-3-pentylamino-maleimide IM-54 was the most effective cell death inhibitor among the compounds tested. IM-54 inhibited necrotic cell death induced by H2O2, but not apoptotic cell death induced by etoposide. These results indicated that this novel cell death inhibitor is distinct from the well-known caspase inhibitor, Z-VAD, which can block apoptotic cell death, but not necrotic cell death. IM-54 is expected to be a powerful bioprobe for clarifying the unique signaling pathway of necrotic cell death. (c) 2005 Elsevier Ltd. All rights reserved.
• Structure–Activity Relationship Study of 3-Amino-2-indolyllactam Derivatives: Development of Inhibitors of Oxidative Stress-Induced Necrosis
  作者：Kosuke Dodo、Kenji Hayamizu、Tadashi Shimizu、Mikiko Sodeoka

  DOI：10.1248/cpb.c16-00259

  日期：——

  Modification of our previously reported selective inhibitor of oxidative stress-induced necrosis, 2-(1H-indol-3-yl)-3-pentylamino-maleimide (IM-54) by regioselective reduction of the C-4 carbonyl group afforded a 3-amino-2-indolyllactam (IL-1) with more potent activity. To examine the structure–activity relationship of IL derivatives, we developed new synthetic routes with flexibility to incorporate a range of substituents at a late stage. The synthesized IL derivatives were evaluated for activity to inhibit necrotic cell death induced by hydrogen peroxide. Among them, IL-12 showed the most potent activity (IC50=49 nM) among the IL and indolylmaleimide (IM) derivatives examined.

  我们之前报道的选择性氧化应激诱导坏死抑制剂2-(1H-吲哚-3-基)-3-戊胺基马来酰亚胺（IM-54）的C-4羰基区域选择性还原，得到了活性更强的3-氨基-2-吲哚基内酰胺（IL-1）。为了研究IL衍生物的构效关系，我们开发了新的合成路线，可以在后期灵活引入多种取代基。合成的IL衍生物进行了抑制过氧化氢诱导细胞坏死活性的评估。其中，IL-12在所检测的IL和吲哚基马来酰亚胺（IM）衍生物中显示出最强的活性（IC50=49 nM）。