4-[[2-[2-(乙酰基氧基)乙基]-2,3-二氢-4-甲基-1,3-二氧-1H-吡咯并[3,4-c]喹啉-8-基]磺酰基]-吗啉 | 745046-84-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 4-[[2-[2-(乙酰基氧基)乙基]-2,3-二氢-4-甲基-1,3-二氧-1H-吡咯并[3,4-c]喹啉-8-基]磺酰基]-吗啉
• 英文名称: ivachtin
• 英文别名: 2-(4-methyl-8-morpholin-4-ylsulfonyl-1,3-dioxopyrrolo[3,4-c]quinolin-2-yl)ethyl acetate
• CAS: 745046-84-8
• 化学式: C₂₀H₂₁N₃O₇S
• mdl: MFCD09971108
• 分子量: 447.469
• InChiKey: MWXJJTMEUGWKKY-UHFFFAOYSA-N

物化性质

• 沸点：
  665.0±65.0 °C(Predicted)
• 密度：
  1.459±0.06 g/cm3(Predicted)
• 溶解度：
  溶解度有限，溶于DMSO或DMF

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  132
• 氢给体数：
  0
• 氢受体数：
  9

制备方法与用途

生物活性

Ivachtin (Caspase-3 Inhibitor VII；化合物 7a) 是一种非肽、非竞争性和可逆的 caspase-3 抑制剂，IC50 值为 23 nM。它对其他胱天蛋白酶具有适度的选择性。

靶点

| Caspase-3 | 23 nM (IC50) |

体外研究

Ivachtin (Caspase-3 Inhibitor VII；化合物 7a；10 μM 和 100 μM 浓度) 在人 Jurkat T 细胞 staurosporine 诱导的凋亡模型中表现出保护作用。

反应信息

• 作为反应物：
  描述：

  4-[[2-[2-(乙酰基氧基)乙基]-2,3-二氢-4-甲基-1,3-二氧-1H-吡咯并[3,4-c]喹啉-8-基]磺酰基]-吗啉 、 对三氟甲基苯甲醛 在 乙酸酐 、 zinc(II) chloride 作用下， 反应 70.0h， 以20%的产率得到Acetic acid 2-{8-(morpholine-4-sulfonyl)-1,3-dioxo-4-[(E)-2-(4-trifluoromethyl-phenyl)-vinyl]-1,3-dihydro-pyrrolo[3,4-c]quinolin-2-yl}-ethyl ester
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of 4-Substituted 2-(2-Acetyloxyethyl)-8-(morpholine- 4-sulfonyl)pyrrolo[3,4-c]quinoline- 1,3-diones as Potent Caspase-3 Inhibitors

  摘要：

  Synthesis, biological evaluation, and SAR dependencies for a series of novel 1,3-dioxo-2,3-dihydro-1H-pyrrolo-[3,4-c]quinoline inhibitors of caspase-3 are described. The inhibitory activity of the synthesized compounds is highly dependent on the nature of 4-substituents on the core scaffold. 4-Methyl-and 4-phenyl-substituted derivatives, which were the most active compounds within this series, inhibited caspase-3 with IC50 of 23 and 27 nM, respectively.

  DOI：

  10.1021/jm048987t
• 作为产物：
  描述：

  4-methyl-8-(morpholin-4-ylsulfonyl)-furo[3,4-c]quinoline-1,3-dione 在 吡啶 作用下， 反应 1.5h， 生成 4-[[2-[2-(乙酰基氧基)乙基]-2,3-二氢-4-甲基-1,3-二氧-1H-吡咯并[3,4-c]喹啉-8-基]磺酰基]-吗啉
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of 4-Substituted 2-(2-Acetyloxyethyl)-8-(morpholine- 4-sulfonyl)pyrrolo[3,4-c]quinoline- 1,3-diones as Potent Caspase-3 Inhibitors

  摘要：

  Synthesis, biological evaluation, and SAR dependencies for a series of novel 1,3-dioxo-2,3-dihydro-1H-pyrrolo-[3,4-c]quinoline inhibitors of caspase-3 are described. The inhibitory activity of the synthesized compounds is highly dependent on the nature of 4-substituents on the core scaffold. 4-Methyl-and 4-phenyl-substituted derivatives, which were the most active compounds within this series, inhibited caspase-3 with IC50 of 23 and 27 nM, respectively.

  DOI：

  10.1021/jm048987t

文献信息

• COMPOSITIONS AND METHODS FOR PRESERVING PLATELET FUNCTION
  申请人：BIOVEC TRANSFUSION, LLC

  公开号：US20150056604A1

  公开（公告）日：2015-02-26

  Compositions and methods for maintaining platelet functionality and extending the shelf-life of platelets are described. Platelet preservation compositions include a photosensitizer and a plurality of platelet preservation agents. A method for preserving platelets and extending their shelf-life includes irradiating a platelet mixture containing a photosensitizer under conditions sufficient to activate the photosensitizer and inactivate microbes in the platelet mixture to form a microbe-depleted platelet preparation. A plurality of platelet preservation agents are added to the microbe-depleted platelet preparation for extending the platelet shelf-life. Prior to transfusion, the photosensitizer and platelet preservation agents can be removed by diafiltration and/or the use of compound adsorption devices.

  本文描述了维持血小板功能和延长血小板货架寿命的组合物和方法。血小板保存组合物包括光敏剂和多种血小板保存剂。一种保存血小板并延长其货架寿命的方法包括在足以激活光敏剂并灭活血小板混合物中的微生物的条件下，照射含有光敏剂的血小板混合物，以形成去除微生物的血小板制备物。在延长血小板货架寿命之前，向去除微生物的血小板制备物中添加多种血小板保存剂。在输血之前，可以通过透析和/或使用化合物吸附装置去除光敏剂和血小板保存剂。
• 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。
• Pyrrolo[3,4-c]quinoline-1,3-diones as potent caspase-3 inhibitors. Synthesis and SAR of 2-substituted 4-methyl-8-(morpholine-4-sulfonyl)-pyrrolo[3,4-c]quinoline-1,3-diones
  作者：Dmitri V. Kravchenko、Volodymyr M. Kysil、Sergey E. Tkachenko、Sergey Maliarchouk、Ilya M. Okun、Alexandre V. Ivachtchenko

  DOI：10.1016/j.ejmech.2005.07.011

  日期：2005.12

  Synthesis, biological evaluation and structure-activity relationships for a series of 2-substituted 4-methyl-8-(morpholine-4-sulfonyl)-1,3dioxo-2,3-dihydro-1H-pyffolo[3,4-c]quinolines are described. These compounds represent a new chemotype of nonpeptide small molecule inhibitors of caspase-3. Among the studied compounds, several potent inhibitors with IC50 in the range of 3-10 nM have been identified. The most active compound within this series, 749} and 758}, inhibited caspase-3 with IC50 = 3 nM. (c) 2005 Elsevier SAS. All rights reserved.
• EP2761000B1
  申请人：——

  公开号：EP2761000B1

  公开（公告）日：2016-03-16
• STABILISATION AND ISOLATION OF EXTRACELLULAR NUCLEIC ACIDS
  申请人：Qiagen GmbH

  公开号：EP2761020B1

  公开（公告）日：2018-06-13