1-(4-(methylsulfonyl)phenyl)-4-phenyl-1H-pyrazole

• 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-(4-(methylsulfonyl)phenyl)-4-phenyl-1H-pyrazole
• 英文别名: 1-(4-Methylsulfonylphenyl)-4-phenylpyrazole
• 化学式: C₁₆H₁₄N₂O₂S
• 分子量: 298.365
• InChiKey: ORBGPQIFBKGVLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  60.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  对氟苯甲砜 在 potassium phosphate 、 二氯双[二叔丁基-(4-二甲基氨基苯基)膦]钯(II) 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 1-(4-(methylsulfonyl)phenyl)-4-phenyl-1H-pyrazole
  参考文献：
  名称：

  Toward the Validation of Maternal Embryonic Leucine Zipper Kinase: Discovery, Optimization of Highly Potent and Selective Inhibitors, and Preliminary Biology Insight

  摘要：

  MELK kinase has been implicated in playing an important role in tumorigenesis. Our previous studies suggested that MELK is involved in the regulation of cell cycle and its genetic depletion leads to growth inhibition in a subset of high MELK-expressing basal-like breast cancer cell lines. Herein we describe the discovery and optimization of novel MELK inhibitors 8a and 8b that recapitulate the cellular effects observed by short hairpin ribonucleic acid (shRNA)-mediated MELK knockdown in cellular models. We also discovered a novel fluorine-induced hydrophobic collapse that locked the ligand in its bioactive conformation and led to a 20-fold gain in potency. These novel pharmacological inhibitors achieved high exposure in vivo and were well tolerated, which may allow further in vivo evaluation.

  DOI：

  10.1021/acs.jmedchem.6b00052

文献信息

• US5756530A
  申请人：——

  公开号：US5756530A

  公开（公告）日：1998-05-26
• Toward the Validation of Maternal Embryonic Leucine Zipper Kinase: Discovery, Optimization of Highly Potent and Selective Inhibitors, and Preliminary Biology Insight
  作者：B. Barry Touré、John Giraldes、Troy Smith、Elizabeth R. Sprague、Yaping Wang、Simon Mathieu、Zhuoliang Chen、Yuji Mishina、Yun Feng、Yan Yan-Neale、Subarna Shakya、Dongshu Chen、Matthew Meyer、David Puleo、J. Tres Brazell、Christopher Straub、David Sage、Kirk Wright、Yanqiu Yuan、Xin Chen、Jose Duca、Sean Kim、Li Tian、Eric Martin、Kristen Hurov、Wenlin Shao

  DOI：10.1021/acs.jmedchem.6b00052

  日期：2016.5.26

  MELK kinase has been implicated in playing an important role in tumorigenesis. Our previous studies suggested that MELK is involved in the regulation of cell cycle and its genetic depletion leads to growth inhibition in a subset of high MELK-expressing basal-like breast cancer cell lines. Herein we describe the discovery and optimization of novel MELK inhibitors 8a and 8b that recapitulate the cellular effects observed by short hairpin ribonucleic acid (shRNA)-mediated MELK knockdown in cellular models. We also discovered a novel fluorine-induced hydrophobic collapse that locked the ligand in its bioactive conformation and led to a 20-fold gain in potency. These novel pharmacological inhibitors achieved high exposure in vivo and were well tolerated, which may allow further in vivo evaluation.