(2E)-1-(2,5-difluorophenyl)-3-phenylbut-2-en-one | 873776-30-8

• 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
• 英文名称: (2E)-1-(2,5-difluorophenyl)-3-phenylbut-2-en-one
• 英文别名: (E)-1-(2,5-difluorophenyl)-3-phenylbut-2-en-1-one
• CAS: 873776-30-8
• 化学式: C₁₆H₁₂F₂O
• 分子量: 258.267
• InChiKey: PKRBOGIYZSDZFR-PKNBQFBNSA-N

物化性质

• 沸点：
  367.3±42.0 °C(Predicted)
• 密度：
  1.184±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2E)-1-(2,5-difluorophenyl)-3-phenylbut-2-en-one 在 一水合肼 作用下， 以 乙醇 为溶剂， 生成 3-(2,5-Difluorophenyl)-5-methyl-5-phenyl-1,4-dihydropyrazole
  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-difluorophenyl)-3-phenylbut-2-en-one
  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

• Mitotic Kinesin Inhibitors
  申请人：Fraley E. Mark

  公开号：US20080032980A1

  公开（公告）日：2008-02-07

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

  本发明涉及二氢吡唑化合物，其可用于治疗细胞增殖性疾病，治疗与KSP动力蛋白活性相关的疾病，并抑制KSP动力蛋白。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：EP1492487B1

  公开（公告）日：2009-11-11
• US7553838B2
  申请人：——

  公开号：US7553838B2

  公开（公告）日：2009-06-30
• US7745639B2
  申请人：——

  公开号：US7745639B2

  公开（公告）日：2010-06-29