(2,2-difluoroethyl)(methyl)amine | 795299-76-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (2,2-difluoroethyl)(methyl)amine
• 英文别名: (2-Aminoethyl)(2,2-difluoroethyl)methylamine；N'-(2,2-difluoroethyl)-N'-methylethane-1,2-diamine
• CAS: 795299-76-2
• 化学式: C₅H₁₂F₂N₂
• mdl: MFCD12768623
• 分子量: 138.16
• InChiKey: HZWVDKDSDLHMCO-UHFFFAOYSA-N

物化性质

• 沸点：
  126.1±30.0 °C(Predicted)
• 密度：
  1.036±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  9
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  格尔德霉素 、 (2,2-difluoroethyl)(methyl)amine 以 1,2-二氯乙烷 为溶剂， 反应 20.0h， 生成 17-[2-(N-methyl-N-2,2-difluoroethylamino)ethyl]amino-17-demethoxygeldanamycin
  参考文献：
  名称：

  Synthesis and biological activities of novel 17-aminogeldanamycin derivatives

  摘要：

  Geldanamycin interferes with the action of heat shock protein 90 (Hsp90) by binding to the N-terminal ATP binding site and inhibiting an essential ATPase activity. In a program directed toward finding potent, water soluble inhibitors of Hsp90, we prepared a library of over sixty 17-alkylamino-17-demethoxygeldanamycin analogs, and compared their affinity for Hsp90, ability to inhibit growth of SKBr3 mammalian cells, and in selected cases, water solubility. Over 20 analogs showed cell growth inhibition potencies similar to that of 17-allylamino-17-demethoxygeldanamycin (17-AAG), the front-runner geldanamycin analog that is currently in multiple clinical trials. Many of these analogs showed water solubility properties that were desirable for formulation. One of the most potent and water-soluble analogs in the series was 17-(2-dimethylaminoethyl)amino-17-demethoxygeldanamycin (17-DMAG), which was independently prepared by the NCI and will soon enter clinical trials. Importantly, the binding affinity of these analogs to the molecular target Hsp90 does not correlate well with their cytotoxicity in SKBr3 cells. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.07.053

文献信息

• Antiprotozoal Structure–Activity Relationships of Synthetic Leucinostatin Derivatives and Elucidation of their Mode of Action
  作者：Michael Brand、Lei Wang、Stefano Agnello、Silvia Gazzola、Flavio M. Gall、Luka Raguž、Marcel Kaiser、Remo S. Schmidt、Amélie Ritschl、Jennifer Jelk、Andrew Hemphill、Pascal Mäser、Peter Bütikofer、Michael Adams、Rainer Riedl

  DOI：10.1002/anie.202102153

  日期：2021.7.5

  understanding. The antiprotozoal SAR matched SAR in phospholipid liposomes, where membrane integrity, leaking, and dynamics were studied. The mode of action is discussed based on a structure–activity analysis of derivatives in efficacy, ultrastructural studies in T. brucei, and artificial membrane models, mimicking membrane stability and membrane potential. The main site of antiprotozoal action of natural

  Leucinostatin A 是迄今为止描述的最有效的抗原虫化合物之一，但人们对其构效关系 (SAR) 知之甚少。我们使用布氏锥虫作为原生动物模型生物来测试合成修饰的衍生物，得到简化但活性相同的化合物2 (ZHAWOC6025) 和4 (ZHAWOC6027)，随后在分子的所有区域进行修饰，以获得深入的 SAR 了解。抗原虫 SAR 与磷脂脂质体中的 SAR 相匹配，研究了膜的完整性、渗漏和动力学。基于衍生物功效的结构活性分析、 T. brucei的超微结构研究以及模拟膜稳定性和膜电位的人工膜模型，讨论了作用模式。超微结构分析、电子显微镜和线粒体染色表明，天然和合成的亮氨抑素的抗原虫作用的主要位点在于线粒体内膜的不稳定。布氏锥虫的长期亚致死暴露（200 次传代）和 12'000 个突变体的 siRNA 筛选未显示出对合成衍生物产生抗性的迹象。
• Synthesis and biological activities of novel 17-aminogeldanamycin derivatives
  作者：Zong-Qiang Tian、Yaoquan Liu、Dan Zhang、Zhan Wang、Steven D. Dong、Christopher W. Carreras、Yiqing Zhou、Giulio Rastelli、Daniel V. Santi、David C. Myles

  DOI：10.1016/j.bmc.2004.07.053

  日期：2004.10

  Geldanamycin interferes with the action of heat shock protein 90 (Hsp90) by binding to the N-terminal ATP binding site and inhibiting an essential ATPase activity. In a program directed toward finding potent, water soluble inhibitors of Hsp90, we prepared a library of over sixty 17-alkylamino-17-demethoxygeldanamycin analogs, and compared their affinity for Hsp90, ability to inhibit growth of SKBr3 mammalian cells, and in selected cases, water solubility. Over 20 analogs showed cell growth inhibition potencies similar to that of 17-allylamino-17-demethoxygeldanamycin (17-AAG), the front-runner geldanamycin analog that is currently in multiple clinical trials. Many of these analogs showed water solubility properties that were desirable for formulation. One of the most potent and water-soluble analogs in the series was 17-(2-dimethylaminoethyl)amino-17-demethoxygeldanamycin (17-DMAG), which was independently prepared by the NCI and will soon enter clinical trials. Importantly, the binding affinity of these analogs to the molecular target Hsp90 does not correlate well with their cytotoxicity in SKBr3 cells. (C) 2004 Elsevier Ltd. All rights reserved.