(+/-)-1-(5-bromo-2-fluorophenyl)-4-(3-hydroxypropyl)-N-methoxy-N-methyl-4-phenyl-4,5-dihydro-1H-pyrazole-3-carboxamide | 895536-74-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (+/-)-1-(5-bromo-2-fluorophenyl)-4-(3-hydroxypropyl)-N-methoxy-N-methyl-4-phenyl-4,5-dihydro-1H-pyrazole-3-carboxamide
• 英文别名: 2-(5-bromo-2-fluorophenyl)-4-(3-hydroxypropyl)-N-methoxy-N-methyl-4-phenyl-3H-pyrazole-5-carboxamide
• CAS: 895536-74-0
• 化学式: C₂₁H₂₃BrFN₃O₃
• 分子量: 464.334
• InChiKey: WQKDVDZHTVIMBH-UHFFFAOYSA-N

物化性质

• 沸点：
  541.8±60.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  65.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+/-)-1-(5-bromo-2-fluorophenyl)-4-(3-hydroxypropyl)-N-methoxy-N-methyl-4-phenyl-4,5-dihydro-1H-pyrazole-3-carboxamide 、 四甲基锡 在 四(三苯基膦)钯 lithium chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以93%的产率得到(+/-)-1-(2-fluoro-5-methylphenyl)-4-(3-hydroxypropyl)-N-methoxy-N-methyl-4-phenyl-4,5-dihydro-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP

  摘要：

  Inspired by previous efforts in the pyrazolobenzoxazine class of KSP inhibitors, the design and synthesis of 1,4-diaryl-4,5-dihydropyrazole inhibitors of KSP are described. Crystallographic evidence of binding mode and in vivo potency data is also highlighted. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.074
• 作为产物：
  描述：

  (+/-)-4-allyl-1-(5-bromo-2-fluorophenyl)-N-methoxy-N-methyl-4-phenyl-4,5-dihydro-1H-pyrazole-3-carboxamide 在 9-borabicyclo[3.3.1]nonane dimer 、 sodium hydroxide 、 双氧水 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 (+/-)-1-(5-bromo-2-fluorophenyl)-4-(3-hydroxypropyl)-N-methoxy-N-methyl-4-phenyl-4,5-dihydro-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP

  摘要：

  Inspired by previous efforts in the pyrazolobenzoxazine class of KSP inhibitors, the design and synthesis of 1,4-diaryl-4,5-dihydropyrazole inhibitors of KSP are described. Crystallographic evidence of binding mode and in vivo potency data is also highlighted. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.074

文献信息

• Mitotic Kinesin Inhibitors
  申请人：Coleman J. Paul

  公开号：US20080045492A1

  公开（公告）日：2008-02-21

  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。该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的癌症的方法。
• WO2006/68933
  申请人：——

  公开号：——

  公开（公告）日：——
• MITOTIC KINESIN INHIBITORS
  申请人：Merck & Co., Inc.

  公开号：EP1831176A2

  公开（公告）日：2007-09-12
• [EN] MITOTIC KINESIN INHIBITORS<br/>[FR] INHIBITEURS DE LA KINESINE MITOTIQUE
  申请人：MERCK & CO INC

  公开号：WO2006068933A2

  公开（公告）日：2006-06-29

  [EN] 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.
  [FR] La présente invention concerne des composés de dihydropyrazole utilisés dans le traitement de maladies prolifératives cellulaires, de troubles associés à l'activité de la kinésine de la protéine KSP et dans l'inhibition de la kinésine de la protéine KSP. Cette invention a aussi pour objet des compositions qui renferment ces composés et leurs méthodes d'utilisation dans le traitement de cancer chez des mammaliens.
• Kinesin spindle protein (KSP) inhibitors. Part 8: Design and synthesis of 1,4-diaryl-4,5-dihydropyrazoles as potent inhibitors of the mitotic kinesin KSP
  作者：Anthony J. Roecker、Paul J. Coleman、Swati P. Mercer、John D. Schreier、Carolyn A. Buser、Eileen S. Walsh、Kelly Hamilton、Robert B. Lobell、Weikang Tao、Ronald E. Diehl、Vicki J. South、Joseph P. Davide、Nancy E. Kohl、Youwei Yan、Lawrence C. Kuo、Chunze Li、Carmen Fernandez-Metzler、Elizabeth A. Mahan、Thomayant Prueksaritanont、George D. Hartman

  DOI：10.1016/j.bmcl.2007.07.074

  日期：2007.10

  Inspired by previous efforts in the pyrazolobenzoxazine class of KSP inhibitors, the design and synthesis of 1,4-diaryl-4,5-dihydropyrazole inhibitors of KSP are described. Crystallographic evidence of binding mode and in vivo potency data is also highlighted. (c) 2007 Elsevier Ltd. All rights reserved.