(2e)-1-(2,5-二氟苯基)-3-苯基-2-丙烯-1-酮 | 877862-83-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 中文名称: (2e)-1-(2,5-二氟苯基)-3-苯基-2-丙烯-1-酮
• 英文名称: (E)-1-(2,5-difluorophenyl)-3-phenylprop-2-en-1-one
• 英文别名: (2E)-1-(2,5-difluorophenyl)-3-phenylprop-2-en-1-one
• CAS: 877862-83-4
• 化学式: C₁₅H₁₀F₂O
• 分子量: 244.241
• InChiKey: WDLARRRQGZDHNR-RMKNXTFCSA-N

物化性质

• 熔点：
  41-43 °C
• 沸点：
  365.9±42.0 °C(Predicted)
• 密度：
  1.232±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 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：
  17.1
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2914700090

反应信息

• 作为反应物：
  描述：

  (2e)-1-(2,5-二氟苯基)-3-苯基-2-丙烯-1-酮 在 一水合肼 作用下， 以 乙醇 为溶剂， 生成
  参考文献：
  名称：

  Kinesin spindle protein (KSP) inhibitors. Part 4: Structure-based design of 5-alkylamino-3,5-diaryl-4,5-dihydropyrazoles as potent, water-soluble inhibitors of the mitotic kinesin KSP

  摘要：

  Molecular modeling in combination with X-ray crystallographic information was employed to identify a region of the kinesin spindle protein (KSP) binding site not fully utilized by our first generation inhibitors. We discovered that by appending a propylamine substituent at the C5 carbon of a dihydropyrazole core, we could effectively fill this unoccupied region of space and engage in a hydrogen-bonding interaction with the enzyme backbone. This change led to a second generation compound with increased potency, a 400-fold enhancement in aqueous solubility at pH 4, and improved dog pharmacokinetics relative to the first generation compound. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.03.040
• 作为产物：
  描述：

  2,5-difluoro-N-methoxy-N-methylbenzamide 在 正丁基锂 、 copper(I) bromide dimethylsulfide complex 作用下， 以 四氢呋喃 为溶剂， 生成 (2e)-1-(2,5-二氟苯基)-3-苯基-2-丙烯-1-酮
  参考文献：
  名称：

  Kinesin spindle protein (KSP) inhibitors. Part 4: Structure-based design of 5-alkylamino-3,5-diaryl-4,5-dihydropyrazoles as potent, water-soluble inhibitors of the mitotic kinesin KSP

  摘要：

  Molecular modeling in combination with X-ray crystallographic information was employed to identify a region of the kinesin spindle protein (KSP) binding site not fully utilized by our first generation inhibitors. We discovered that by appending a propylamine substituent at the C5 carbon of a dihydropyrazole core, we could effectively fill this unoccupied region of space and engage in a hydrogen-bonding interaction with the enzyme backbone. This change led to a second generation compound with increased potency, a 400-fold enhancement in aqueous solubility at pH 4, and improved dog pharmacokinetics relative to the first generation compound. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.03.040

文献信息

• Predicting the photoinduced electron transfer thermodynamics in polyfluorinated 1,3,5-triarylpyrazolines based on multiple linear free energy relationships
  作者：Manjusha Verma、Aneese F. Chaudhry、Christoph J. Fahrni

  DOI：10.1039/b821042j

  日期：——

  The photophysical properties of 1,3,5-triarylpyrazolines are strongly influenced by the nature and position of substituents attached to the aryl-rings, rendering this fluorophore platform well suited for the design of fluorescent probes utilizing a photoinduced electron transfer (PET) switching mechanism. To explore the tunability of two key parameters that govern the PET thermodynamics, the excited state energy ΔE00 and the acceptor potential E(A/A−), a library of polyfluoro-substituted 1,3-diaryl-5-phenyl-pyrazolines was synthesized and characterized. The observed trends for the PET parameters were effectively captured through multiple Hammett linear free energy relationships (LFER) using a set of independent substituent constants for each of the two aryl rings. Given the lack of experimental Hammett constants for polyfluoro-substituted aromatics, theoretically derived constants based on the electrostatic potential at the nucleus (EPN) of carbon atoms were employed as quantum chemical descriptors. The performance of the LFER was evaluated with a set of compounds that were not included in the training set, yielding a mean unsigned error of 0.05 eV for the prediction of the combined PET parameters. The outlined LFER approach should be well suited for designing and optimizing the performance of cation-responsive 1,3,5-triarylpyrazolines.

  1,3,5-三芳基吡唑啉的光物理特性受到附着在芳环上的取代基的性质和位置的强烈影响，使得这一荧光基团平台非常适合设计利用光诱导电子转移（PET）开关机制的荧光探针。为了探索控制PET热力学的两个关键参数的可调性，即激发态能量ΔE00和受体电势E(A/A−)，研究人员合成并表征了一系列多氟取代的1,3-二芳基-5-苯基-吡唑啉。通过对每个芳环使用一组独立的取代基常数，观察到的PET参数趋势可以通过多个Hammett线性自由能关系（LFER）有效捕捉。由于缺乏多氟取代芳香族化合物的实验Hammett常数，研究人员使用基于碳原子核电势（EPN）理论推导出的常数作为量子化学描述符。用一组不包括在训练集中的化合物评估LFER的性能，预测的结合PET参数的平均无符号误差为0.05 eV。所述的LFER方法非常适合设计和优化阳离子响应的1,3,5-三芳基吡唑啉的性能。
• Mitotic Kinesin Inhibitors
  申请人：Fraley Mark E.

  公开号：US20090005418A1

  公开（公告）日：2009-01-01

  The present invention relates to dihydroisoxazoles that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention also relates to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.

  本发明涉及用于治疗细胞增殖性疾病、治疗与KSP马达蛋白活性相关的疾病以及抑制KSP马达蛋白的二氢异噁唑化合物。本发明还涉及包含这些化合物的组合物以及使用它们治疗哺乳动物癌症的方法。
• Mitotic kinesin inhibitors
  申请人：Merck & Co., Inc.

  公开号：US07732472B2

  公开（公告）日：2010-06-08

  The present invention relates to dihydroisoxazoles that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention also relates to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.

  本发明涉及二氢异噁唑，其对治疗细胞增殖性疾病，治疗与KSP动力蛋白活性相关的紊乱以及抑制KSP动力蛋白具有用处。本发明还涉及包含这些化合物的组合物以及使用它们治疗哺乳动物癌症的方法。
• [EN] MITOTIC KINESIN INHIBITORS<br/>[FR] INHIBITEURS DE KINESINES MITOTIQUES
  申请人：MERCK & CO INC

  公开号：WO2006023440A3

  公开（公告）日：2007-03-15
• MITOTIC KINESIN INHIBITORS
  申请人：Merck & Co., Inc.

  公开号：EP1492487B1

  公开（公告）日：2009-11-11