5-(2-bromoprop-2-enoylamino)-1H-indole-2-carboxylic acid | 294174-53-1

• 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
• 英文名称: 5-(2-bromoprop-2-enoylamino)-1H-indole-2-carboxylic acid
• CAS: 294174-53-1
• 化学式: C₁₂H₉BrN₂O₃
• 分子量: 309.119
• InChiKey: YNNMLKLJHWASMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(2-bromoprop-2-enoylamino)-1H-indole-2-carboxylic acid 在 盐酸 、 氯化亚砜 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 5-(2-Bromo-acryloylamino)-1H-indole-2-carboxylic acid (2-{[5-(2-biphenyl-4-yl-4-methylene-5-oxo-tetrahydro-furan-2-ylmethoxy)-2-methyl-2H-pyrazole-3-carbonyl]-amino}-ethyl)-amide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Hybrid Molecules Containing α-Methylene-γ-Butyrolactones and α-Bromoacryloyl Moieties

  摘要：

  The synthesis and biological activity of hybrids 8-18 prepared combining alpha-methylene-gamma-butyrolactones and alpha-bromoacryloylamides have been described and their structure -activity relationships discussed. All these heterobifunctional compounds demonstrate good antileukemic activity, significantly superior to that of both alkylating units alone. Using the human leukemia HL-60 cell line, selected compounds 10, 11, 13, and 17 were found to induce morphological changes and internucleosomal DNA fragmentation characteristic of apoptotic cell death.

  DOI：

  10.1021/jm058012o
• 作为产物：
  描述：

  5-硝基吲哚-2-甲酸 在 palladium on activated charcoal 苄基三乙基氯化铵 、 氢气 、 potassium carbonate 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、379.21 kPa 条件下， 反应 21.0h， 生成 5-(2-bromoprop-2-enoylamino)-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  二氢新霉素二苯并杂环衍生物的合成及抗肿瘤活性

  摘要：

  设计，合成以及一系列新颖的化合物（13-22和34）的体内和体外抗白血病活性，其中不同的苯并杂环环带有氮芥子基或苯甲酰基氮芥子基或α-溴丙烯酰基烷基化据报道，部分被束缚在双霉素框架上，并讨论了构效关系。通过将氮芥子取代的，苯甲酰基氮芥子取代的或α-溴丙烯酰基取代的苯并杂环的羧酸23-32与去甲酰基二胺（33）或在一种情况下与其二吡咯类似物35偶联，可以制备新的衍生物。例外，带有相同烷基化部分的化合物的活性受苯并杂环上杂原子的种类的影响很小。所有新化合物 除了一个例外，它显示出对L1210鼠白血病细胞系的体外活性与塔利莫司汀相当或更好。氮芥子和α-溴丙烯酰基部分直接与苯并杂环环相连的化合物显示出强的细胞毒活性（IC（50）为2至14 nM），而苯并杂环的苯甲酰氮芥子衍生物显示出降低的细胞毒活性，其中一种该簇的化合物（16）是没有明显活性的唯一衍生物。化合物18（一种双氮霉素的5-氮芥子气N-

  DOI：

  10.1021/jm9911229

文献信息

• Synthesis and growth inhibition activity of α-Bromoacrylic heterocyclic and benzoheterocyclic derivatives of distamycin A modified on the amidino moiety
  作者：Pier Giovanni Baraldi、Italo Beria、Paolo Cozzi、Nicoletta Bianchi、Roberto Gambari、Romeo Romagnoli

  DOI：10.1016/s0968-0896(02)00533-3

  日期：2003.3

  The design, synthesis and in vitro activities of novel alpha-bromoacryloyl pyrazole, imidazole and benzoheterocyclic derivatives of distamycin A, in which the amidino moiety has been replaced by moieties of different physico-chemical features are described, and the structure-activity relationships are discussed. In spite of the relevance of these modifications on the distamycin frame, these derivatives showed significant growth inhibitory activity against mouse leukemia L1210 cells. Therefore, the presence of the amidino moiety, and in general of a basic moiety, is not an absolute requirement for biological activity of alpha-bromoacrylic derivatives of distamycin. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Hybrid molecules containing benzo[4,5]imidazo[1,2-d][1,2,4]thiadiazole and α-bromoacryloyl moieties as potent apoptosis inducers on human myeloid leukaemia cells
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Maria Dora Carrion、Olga Cruz-Lopez、Delia Preti、Mojgan Aghazadeh Tabrizi、Francesca Fruttarolo、Jörg Heilmann、Jaime Bermejo、Francisco Estévez

  DOI：10.1016/j.bmcl.2007.02.048

  日期：2007.5

  The synthesis and biological activity of a series of hybrids 1-5 prepared combining a benzo[4,5]imidazo[1,2-d][1,2,4]thiadiazole and different benzoheterocyclic alpha-bromoacryloyl amides have been described and their structure-activity relationships discussed. All these hetero-bifunctional compounds were highly cytotoxic against the human myeloid leukaemia cell lines HL-60 and U937 (IC50 0.24-1.72 mu M), significantly superior to that of both alkylating units alone. In human myeloid leukaemia HL-60 cells we observed that these compounds suppress survival and proliferation by triggering morphological changes and internucleosomal DNA fragmentation characteristic of apoptotic cell death. The apoptosis induced by these compounds is mediated by caspase-3 activation and is also associated to an early release of cytochrome c from the mitochondria. (c) 2007 Elsevier Ltd. All rights reserved.
• BENZOHETEROCYCLIC DISTAMYCIN DERIVATIVES, PROCESS FOR PREPARING THEM, AND THEIR USE AS ANTITUMOR AND ANTIVIRAL AGENTS
  申请人：Pharmacia Italia S.p.A.

  公开号：EP0937070B1

  公开（公告）日：2003-12-03
• BENZOHETEROCYCLIC DISTAMYCIN DERIVATIVES, PROCESS FOR PREPARING THEM, AND THEIR USE AS ANTITUMOR AGENTS
  申请人：PHARMACIA & UPJOHN S.p.A.

  公开号：EP1064281A1

  公开（公告）日：2001-01-03
• US6153642A
  申请人：——

  公开号：US6153642A

  公开（公告）日：2000-11-28