5-异氰酰基-1-甲基吲哚啉 | 921938-71-8

• 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: 5-异氰酰基-1-甲基吲哚啉
• 英文名称: 5-isocyanato-1-methylindoline
• 英文别名: 5-isocyanato-1-methyl-2,3-dihydroindole
• CAS: 921938-71-8
• 化学式: C₁₀H₁₀N₂O
• mdl: MFCD09879912
• 分子量: 174.202
• InChiKey: ZHBVXJDYCNQFSO-UHFFFAOYSA-N

物化性质

• 沸点：
  310.3±35.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-异氰酰基-1-甲基吲哚啉 、 6-氨基-1,4-二氢-4-氧代-2-喹啉羧酸甲酯 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 methyl 6-[(1-methyl-2,3-dihydroindol-5-yl)carbamoylamino]-4-oxo-1H-quinoline-2-carboxylate
  参考文献：
  名称：

  Novel vitexin-inspired scaffold against leukemia

  摘要：

  Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children. Up to a quarter of ALL patients relapse and face poor prognosis. To identify new compound leads, we conducted a phenotypic screen using terrestrial natural product (NP) fractions against immortalized ALL cellular models.We identified vitexin, a flavonoid, as a promising hit with biological activity (EC50 = 30 mu M) in pre-B cell ALL models with no toxicity against normal human tissue (BJ cells) at the tested concentrations. To develop more potent compounds against ALL and elucidate its potential mode of action, a vitexin-inspired compound library was synthesized. Thus, we developed an improved and scalable protocol for the direct synthesis of 4-quinolone core heterocycles containing an N-sulfonamide using a one-pot condensation reaction protocol. The newly generated compounds represent a novel molecular scaffold against ALL as exemplified by compounds 13 and 15, which demonstrated EC50 values in the low micromolar range (0.3-10 mu M) with little to no toxicity in normal cellular models. Computational studies support the hypothesis that these compounds are potential CDK inhibitors. The compounds induced apoptosis, caused cell arrest at G0/G1 and G2/M, and induced ROS in cancer cells. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.01.004

文献信息

• Substituted Urea Depsipeptide Analogs as Activators of the CLPP Endopeptidase
  申请人：St. Jude Children's Research Hospital

  公开号：US20180079784A1

  公开（公告）日：2018-03-22

  In one aspect, the invention relates to substituted urea depsipeptide analogs, derivatives thereof, and related compounds, which are useful as activators with the ClpP endopeptidease; synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating infectious disease using the compounds and compositions. This abstract is intended as a scanning tool for purposes of search in the particular art and is not intended to be limiting of the present invention.

  在一个方面，该发明涉及替代脲depsipeptide类似物，其衍生物以及相关化合物，这些化合物可作为ClpP内肽酶的激活剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗传染病的方法。本摘要旨在作为特定领域搜索的扫描工具，并不意味着对本发明的限制。
• Diaryl urea analogues of SB-334867 as orexin-1 receptor antagonists
  作者：David A. Perrey、Brian P. Gilmour、Scott P. Runyon、Brian F. Thomas、Yanan Zhang

  DOI：10.1016/j.bmcl.2011.03.048

  日期：2011.5

  As a part of our program to develop OX1–CB1 bivalent ligands, we required a better understanding of the basic structure–activity relationships (SARs) of orexin antagonists. A series of SB-334867 analogues were synthesized and evaluated in calcium mobilization assays. SAR results suggest that the 2-methylbenzoxazole moiety may be replaced with a disubstituted 4-aminophenyl group without loss of activity

  作为我们开发 OX1-CB1 二价配体计划的一部分，我们需要更好地了解食欲素拮抗剂的基本构效关系 (SAR)。合成了一系列 SB-334867 类似物，并在钙动员测定中进行了评估。SAR 结果表明，2-甲基苯并恶唑部分可以被双取代的 4-氨基苯基取代而不会失去活性，并且缺电子系统通常在 1,5-萘啶部分用于 OX1 拮抗剂活性。特别是，较大的潜在接头如正己基的取代提供了化合物33与先导化合物 SB-334867 相比，对 OX1 受体具有同等活性。这些化合物在开发靶向orexin-1受体及其潜在异源二聚体的配体方面应该具有价值。
• SUBSTITUTED UREA DEPSIPEPTIDE ANALOGS AS ACTIVATORS OF THE CLPP ENDOPEPTIDASE
  申请人：ST. JUDE CHILDREN'S RESEARCH HOSPITAL

  公开号：US20160200770A1

  公开（公告）日：2016-07-14

  In one aspect, the invention relates to substituted urea depsipeptide analogs, derivatives thereof, and related compounds, which are useful as activators the ClpP endopeptidease; synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating infectious disease using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，该发明涉及替代脲depsipeptide类似物、其衍生物和相关化合物，这些化合物可作为ClpP内肽酶的激活剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗传染病的方法。本摘要旨在作为在特定领域搜索的扫描工具，并不意味着对本发明的限制。
• Substituted urea depsipeptide analogs as activators of the CLPP endopeptidase
  申请人：St. Jude Children's Research Hospital

  公开号：US10100090B2

  公开（公告）日：2018-10-16

  In one aspect, the invention relates to substituted urea depsipeptide analogs, derivatives thereof, and related compounds, which are useful as activators with the ClpP endopeptidase; synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating infectious disease using the compounds and compositions. This abstract is intended as a scanning tool for purposes of search in the particular art and is not intended to be limiting of the present invention.

  在一个方面，本发明涉及取代的脲去肽类似物、其衍生物和相关化合物，这些化合物可用作 ClpP 内肽酶的激活剂；制造这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗传染性疾病的方法。本摘要旨在作为在特定技术领域进行搜索的扫描工具，并非对本发明的限制。
• Substituted urea depsipeptide analogs as activators of the ClpP endopeptidase
  申请人：ST. JUDE CHILDREN'S RESEARCH HOSPITAL

  公开号：US10676510B2

  公开（公告）日：2020-06-09

  In one aspect, the invention relates to substituted urea depsipeptide analogs, derivatives thereof, and related compounds, which are useful as activators the C1pP endopeptidease; synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating infectious disease using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，本发明涉及取代的脲去肽类似物、其衍生物和相关化合物，它们可用作 C1pP 内肽酶的激活剂；制造这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗传染病的方法。本摘要旨在作为在特定技术领域进行检索的扫描工具，并非对本发明的限制。