ethyl 4-(4-(4-acrylamido-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxamido)butanoate | 1335228-80-2

• 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
• 英文名称: ethyl 4-(4-(4-acrylamido-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxamido)butanoate
• 英文别名: ethyl 4-[4-(4-acrylamido-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxamido]butanoate
• CAS: 1335228-80-2
• 化学式: C₂₁H₂₇N₅O₅
• 分子量: 429.476
• InChiKey: YDOZRTVIXBWMFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.81
• 重原子数：
  31.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  123.46
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ethyl 4-(4-(4-acrylamido-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxamido)butanoate 在 sodium hydroxide 、 盐酸 作用下， 以 水 、 丙酮 为溶剂， 反应 0.5h， 以83%的产率得到4-(4-(4-acrylamido-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxamido)butanoic acid
  参考文献：
  名称：

  DNA site-specific N3-adenine methylation targeted to estrogen receptor-positive cells

  摘要：

  A compound that can target cells expressing the estrogen receptor (ER), and produce predominantly 3-MeA adducts in those cells has been designed and synthesized. This compound produces mainly the 3-MeA adduct upon reaction with calf thymus DNA, and binds to the ER with a relative binding affinity of 51% (estradiol = 100%). The compound is toxic to ER-expressing MCF-7 breast cancer cells, and pretreatment with the ER antagonist fulvestrant abrogates the toxicity. Pre-treatment of MCF-7 cells with netropsin, which inhibits N3-adenine methylation by the compound, resulted in a threefold decrease in the toxicity. These results demonstrate the feasibility of this strategy for producing 3-MeA adducts in targeted cells. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.07.026
• 作为产物：
  描述：

  Ethyl 4-[(4-amino-1-methylpyrrole-2-carbonyl)amino]butanoate 在 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 乙酸乙酯 为溶剂， -40.0~20.0 ℃ 、482.64 kPa 条件下， 反应 72.0h， 生成 ethyl 4-(4-(4-acrylamido-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxamido)butanoate
  参考文献：
  名称：

  DNA site-specific N3-adenine methylation targeted to estrogen receptor-positive cells

  摘要：

  A compound that can target cells expressing the estrogen receptor (ER), and produce predominantly 3-MeA adducts in those cells has been designed and synthesized. This compound produces mainly the 3-MeA adduct upon reaction with calf thymus DNA, and binds to the ER with a relative binding affinity of 51% (estradiol = 100%). The compound is toxic to ER-expressing MCF-7 breast cancer cells, and pretreatment with the ER antagonist fulvestrant abrogates the toxicity. Pre-treatment of MCF-7 cells with netropsin, which inhibits N3-adenine methylation by the compound, resulted in a threefold decrease in the toxicity. These results demonstrate the feasibility of this strategy for producing 3-MeA adducts in targeted cells. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.07.026

文献信息

• Glycoconjugated Site-Selective DNA-Methylating Agent Targeting Glucose Transporters on Glioma Cells
  作者：Mairin K. Buchanan、Chase N. Needham、Nina E. Neill、Maria C. White、Charles B. Kelly、Kelly Mastro-Kishton、Lacie M. Chauvigne-Hines、Tyler J. Goodwin、Andrew L. McIver、Libero J. Bartolotti、Arthur R. Frampton、Andrea J. Bourdelais、Sridhar Varadarajan

  DOI：10.1021/acs.biochem.6b01075

  日期：2017.1.17

  selective uptake via glucose transporters, which are overexpressed in most cancers. The design features of the molecule, its synthesis, its reactivity with DNA, and its toxicity in human glioblastoma cells are reported here. In this molecule, a glucosamine unit, which can facilitate uptake via glucose transporters, is conjugated to one end of a bispyrrole triamide unit, which is known to bind to the

  脱氧核糖核酸烷基化药物继续仍然是抵抗癌症的武器库中的重要武器。然而，由于它们引起的不加区别的DNA损伤以及它们不能特异性地靶向癌细胞，它们通常遭受若干缺点。我们已经开发出一种策略，通过设计一种可以靶向癌细胞的位点特异性DNA甲基化剂来克服当前DNA烷基化化疗药物的不足，因为它可以通过葡萄糖转运蛋白选择性地摄取，而葡萄糖转运蛋白在大多数癌症中都是过表达的。本文报道了该分子的设计特征，其合成，与DNA的反应性及其在人胶质母细胞瘤细胞中的毒性。在该分子中，可通过葡萄糖转运蛋白促进摄取的葡萄糖胺单元与双吡咯三酰胺单元的一端偶联，已知它会在富含A / T的区域与DNA的小沟结合。磺酸甲酯部分被束缚在双吡咯单元的另一端，以用作DNA甲基化剂。该分子与DNA反应后仅产生N3-甲基腺嘌呤加合物，并且对抗治疗的人成胶质细胞瘤细胞的毒性要比食品和药物管理局批准的糖化DNA甲基化药物链霉菌素高。使用我们分子的荧