双吲哚马来酰亚胺 V | 113963-68-1

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 双吲哚马来酰亚胺 V
• 中文别名: 双吲哚马来酰亚胺V；双吲哚马来酰亚胺；1-甲基-3,4-双(1H-吲哚-3-基)马来酰亚胺；-甲基-3,4-双(1H-吲哚-3-基)马来酰亚胺
• 英文名称: bisindolylmaleimide V
• 英文别名: 3,4-bis-(3'-indolyl)-1-methyl-pyrrole-2,5-dione；2,3-bis<1H-indol-3-yl>-N-methylmaleimide；3,4-di(1H-indol-3-yl)-1-methyl-1H-pyrrole-2,5-dione；3,4-di-1H-Indol-3-yl-1-methyl-1H-pyrrole-2,5-dione；1-methyl-3,4-bis(1H-indol-3-yl)pyrrole-2,5-dione；3,4-bis(1H-indol-3-yl)-1-methylpyrrole-2,5-dione
• CAS: 113963-68-1
• 化学式: C₂₁H₁₅N₃O₂
• 分子量: 341.369
• InChiKey: SWAWYMIKGOHZMR-UHFFFAOYSA-N

物化性质

• 熔点：
  >260 °C
• 沸点：
  655.7±55.0 °C(Predicted)
• 密度：
  1.450±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO
• 稳定性/保质期：

  密封储存，存放在阴凉干燥的仓库中。最佳冷藏温度为-20°C。

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  69
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• WGK Germany：
  3
• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  在常温常压下保持稳定，应避免与强氧化剂接触。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Bisindolylmaleimide v
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: Bisindolylmaleimide v
CAS number: 113963-68-1

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C21H15N3O2
Molecular weight: 341.4

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

概述

双吲哚马来酰亚胺衍生物中，包括双吲哚马来酰亚胺V。这类化合物以其先导物Staurosporine为基础设计，并且表现出良好的生物活性。由于与吲哚咔唑类衍生物在合成上的相关性，它们也被归入吲哚咔唑类化合物。

药理作用

1986年，双吲哚马来酰亚胺V首次被发现具有抗真菌、抗高血压、抗肿瘤和抑制血小板聚集等多种药理作用。吲哚咔唑类化合物的抗肿瘤活性主要靶点涉及多种与细胞周期相关的激酶、细胞核拓扑异构酶（Topoisomerase，Top），以及与肿瘤细胞生长或凋亡有关的其他酶。

用途

双吲哚马来酰亚胺V主要用于其显著的抗肿瘤活性。

反应信息

• 作为反应物：
  描述：

  双吲哚马来酰亚胺 V 在 氢氧化钾 、 盐酸羟胺 、 potassium carbonate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 1-Hydroxy-2,3-bis(3-indolyl)-3-pyrrolin-2,5-dione
  参考文献：
  名称：

  Inhibitors of protein kinase C. 1. 2,3-bisarylmaleimides

  摘要：

  The design and synthesis of a series of novel inhibitors of protein kinase C (PKC) is described. These 2,3-bisarylznaleimides were derived from the structural lead provided by the indolocarbazoles, staurosporine and K252a. Optimum activity required the imide NH, both carbonyl groups, and the olefinic bond of the maleimide ring. 2,3-Bisindolylmaleimides were the most active, and the potency of these was improved by a chloro substituent at the 5-position of one indole ring (compound 28, IC50 0.11-mu-M). In a series of (phenylindolyl)maleimides, nitro compound 74 was most active (IC50 0.67-mu-M). Naphthalene 19 and benzothiophene 21 showed greater than 100-fold selectivity for inhibition of PKC over the closely related cAMP-dependent protein kinase (PKA).

  DOI：

  10.1021/jm00079a024
• 作为产物：
  描述：

  吲哚-3-乙醛酸甲酯 在 potassium tert-butylate 、 potassium hydroxide 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 5.0h， 生成 双吲哚马来酰亚胺 V
  参考文献：
  名称：

  Synthesis and properties of novel heat-resistant fluorescent conjugated polymers with bisindolylmaleimide

  摘要：

  Conjugated polymers with bisindolylmaleimide (BIM) backbone are obtained by the condensation polymerization of methyl and octanyl N-substituted BIMs with 4,4'-difluoro-diphenylsulfone and 4,4'-difluoro-diphenylketone. The structures of polymers are confirmed by FFIR and NMR spectroscopy. The polymers exhibit both high glass transition temperatures (T-g > 175 degrees C) and high decomposition temperatures (T-5 > 395 degrees C). Meanwhile, The UV-vis absorption and fluorescence spectra of the polymers are similar to the corresponding substituted BlMs. The quantum chemistry calculations indicate that the first excited states of polymers are mostly contributed by BIM structures. (C) 2017 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.cclet.2017.08.019
• 作为试剂：
  描述：

  双吲哚马来酰亚胺 V 、 2-[4-[Tert-butyl(diphenyl)silyl]oxy-1-trityloxybutan-2-yl]oxyethyl methanesulfonate 在 双吲哚马来酰亚胺 V 作用下， 生成 3-[1-[2-[4-[tert-butyl(diphenyl)silyl]oxy-1-trityloxybutan-2-yl]oxyethyl]indol-3-yl]-4-(1H-indol-3-yl)-1-methylpyrrole-2,5-dione 、 3,4-Bis[1-[2-[4-[tert-butyl(diphenyl)silyl]oxy-1-trityloxybutan-2-yl]oxyethyl]indol-3-yl]-1-methylpyrrole-2,5-dione
  参考文献：
  名称：

  J. Org. Chem. 1998, 63, 1961-1973

  摘要：

  DOI：

文献信息

• 3,4-二(3-吲哚)-2,5-二酮-3-吡咯啉亚胺类 化合物及其制备方法和应用
  申请人：河南师范大学

  公开号：CN104496970B

  公开（公告）日：2017-01-11

  本发明公开了一种3,4‑二（3‑吲哚）‑2,5‑二酮‑3‑吡咯啉亚胺类化合物及其制备方法和在抗癌药物中的应用。本发明的技术方案要点为：3,4‑二（3‑吲哚）‑2,5‑二酮‑3‑吡咯啉亚胺类化合物，是以醛类化合物R‑CHO和1‑氨基‑3,4‑二(3‑吲哚)‑3‑吡咯啉‑2,5‑二酮为原料制备而成的，其结构通式如下：。本发明还公开了该3,4‑二（3‑吲哚）‑2,5‑二酮‑3‑吡咯啉亚胺类化合物的制备方法及其在抗癌药物中的应用。本发明的制备方法原料价廉易得，操作简单，制备的3,4‑二（3‑吲哚）‑2,5‑二酮‑3‑吡咯啉亚胺类化合物具有较好的生物活性，在制备抗癌药物化合物中具有较好的应用前景。
• 具有抗癌活性的3,4-二（3-吲哚）-2,5-二酮- 1-吡咯胺硫脲类化合物及其制备方法和应用
  申请人：河南师范大学

  公开号：CN104710412B

  公开（公告）日：2017-03-22

  本发明公开了一种具有抗癌活性的3,4‑二（3‑吲哚）‑2,5‑二酮‑1‑吡咯胺硫脲类化合物及其制备方法和应用。本发明的技术方案要点为：具有抗癌活性的3,4‑二（3‑吲哚）‑2,5‑二酮‑1‑吡咯胺硫脲类化合物，是以取代异硫氰酸酯类化合物R‑NCS和1‑氨基‑3,4‑二(3‑吲哚)‑3‑吡咯啉‑2,5‑二酮为原料制备而成的，其结构通式如下：。本发明还公开了该具有抗癌活性的3,4‑二（3‑吲哚）‑2,5‑二酮‑1‑吡咯胺硫脲类化合物的制备方法及其抗癌活性。本发明的制备方法原料价廉易得，操作简单，制备的3,4‑二（3‑吲哚）‑2,5‑二酮‑1‑吡咯胺硫脲类化合物具有较好的生物活性，在制备抗癌药物化合物中具有较好的应用前景。
• Pyrrole derivatives and cell death inhibitors
  申请人：Sagami Chemical Research Center

  公开号：US06589977B1

  公开（公告）日：2003-07-08

  Bisindolylpyrrole derivatives represented by general formula [I] which are useful in inhibiting cell death and expected as being useful as preventives and remedies for the progress of various diseases in the progress and worsening of which cell death participates; and cell death inhibitors, drugs and cell/tissue/organ preservatives containing as the active ingredient these derivatives or pharmaceutically acceptable salts thereof.

  一般公式为[I]的双吲哚吡咯衍生物在抑制细胞死亡方面具有用处，并被期望作为预防和治疗各种疾病进展中细胞死亡参与的进展和恶化的药物；以及包含这些衍生物或其药学上可接受的盐作为活性成分的细胞死亡抑制剂、药物和细胞/组织/器官保护剂。
• Syntheses and Biological Activities of Rebeccamycin Analogues with Uncommon Sugars
  作者：Guisheng Zhang、Jie Shen、Hao Cheng、Lizhi Zhu、Lanyan Fang、Sanzhong Luo、Mark T. Muller、Gun Eui Lee、Lijun Wei、Yuguo Du、Duxin Sun、Peng George Wang

  DOI：10.1021/jm0493764

  日期：2005.4.1

  analogues with various uncommon sugars showed distinct cytotoxicities and topo I targeting activities. The activity of compounds with 2-deoxyglucose (8 and 9) > compounds with 2,6-deoxyglucose (5 and 6) > compounds with 2,3,6-deoxyglucose (10). Furthermore, the anticancer activity of compounds correlated with their ability to target endogenous topo I. These results suggest that the sugar moiety, especially

  已经合成了包含罕见糖和在酰亚胺氮上的取代的瑞贝卡霉素类似物。在结肠癌和白血病细胞中测试了它们的细胞毒性。使用Hela细胞中拓扑异构酶生物测定的体内复合物检查了它们靶向拓扑异构酶I的能力。与糖苷配基1相比，具有各种糖基的修饰化合物显示出更强的细胞毒性和topo I靶向能力。另外，具有多种罕见糖的瑞贝卡霉素类似物显示出独特的细胞毒性和topo I靶向活性。具有2-脱氧葡萄糖的化合物（8和9）>具有2,6-脱氧葡萄糖的化合物（5和6）>具有2,3,6-脱氧葡萄糖的化合物（10）的活性。此外，化合物的抗癌活性与其靶向内源性topo I的能力有关。
• Regiocontrolled Synthesis of the Antitumor Antibiotic AT2433-A1
  作者：John D. Chisholm、David L. Van Vranken

  DOI：10.1021/jo000911r

  日期：2000.11.1

  The indolo[2,3-a]carbazole glycosides are potent antitumor antibiotics currently undergoing clinical trials for the treatment of numerous types of cancer. AT2433-A1 is the most complex member of this family of compounds possessing a unique disaccharide with a sensitive aminodeoxysugar and an unsymmetric aglycon. The synthesis of this natural product requires a method for glycosylation that sets the

  吲哚[2，3-a]咔唑糖苷是有效的抗肿瘤抗生素，目前正接受临床试验以治疗多种类型的癌症。AT2433-A1是该化合物家族中最复杂的成员，具有独特的二糖以及敏感的氨基脱氧糖和不对称糖苷配基。这种天然产物的合成需要糖基化的方法，该方法设定异头异构中心的立体化学和糖苷配基的区域化学。这些目标是通过对bis-3，4-（3-吲哚基）琥珀酰亚胺进行曼尼希环化反应而得到的，主要的二氢吲哚中间体可以与复杂的碳水化合物被立体选择性地糖基化，而没有羟基的保护或活化。通过在动力学或热力学条件之间进行选择，可以精确地控制曼尼希环化反应的区域化学。该策略最终导致抗肿瘤抗生素AT2433-A1的首次合成。