4-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)sulfonyl)aniline | 1541194-18-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)sulfonyl)aniline
• CAS: 1541194-18-6
• 化学式: C₁₄H₁₇N₃O₃S
• 分子量: 307.373
• InChiKey: CDNROUVDCXFEMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.65
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  87.21
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  4-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)sulfonyl)aniline 、 2-(pyridin-3-yl)cyclopropane-1-carbonyl chloride 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 trans-2-(pyridin-3-yl)-N-(4-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)sulfonyl)phenyl)cyclopropanecarboxamide
  参考文献：
  名称：

  Fragment-Based Identification of Amides Derived from trans-2-(Pyridin-3-yl)cyclopropanecarboxylic Acid as Potent Inhibitors of Human Nicotinamide Phosphoribosyltransferase (NAMPT)

  摘要：

  Potent, trans-2-(pyridin-3-yl)cyclopropane-carboxamide-containing inhibitors of the human nicotinamide phosphoribosyltransferase (NAMPT) enzyme were identified using fragment-based screening and structure-based design techniques. Multiple crystal structures were obtained of initial fragment leads, and this structural information was utilized to improve the biochemical and cell-based potency of the associated molecules. Many of the optimized compounds exhibited nanomolar antiproliferative activities against human tumor lines in in vitro cell culture experiments. In a key example, a fragment lead (13, K-D = 51 mu M) was elaborated into a potent NAMPT inhibitor (39, NAMPT IC50 = 0.0051 mu M, A2780 cell culture IC50 = 0.000 49 mu M) which demonstrated encouraging in vivo efficacy in an HT-1080 mouse xenograft tumor model.

  DOI：

  10.1021/jm4015108
• 作为产物：
  描述：

  4-溴四氢吡喃 在 正丁基锂 、 氢气 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 为溶剂， 反应 21.5h， 生成 4-((1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)sulfonyl)aniline
  参考文献：
  名称：

  Fragment-Based Identification of Amides Derived from trans-2-(Pyridin-3-yl)cyclopropanecarboxylic Acid as Potent Inhibitors of Human Nicotinamide Phosphoribosyltransferase (NAMPT)

  摘要：

  Potent, trans-2-(pyridin-3-yl)cyclopropane-carboxamide-containing inhibitors of the human nicotinamide phosphoribosyltransferase (NAMPT) enzyme were identified using fragment-based screening and structure-based design techniques. Multiple crystal structures were obtained of initial fragment leads, and this structural information was utilized to improve the biochemical and cell-based potency of the associated molecules. Many of the optimized compounds exhibited nanomolar antiproliferative activities against human tumor lines in in vitro cell culture experiments. In a key example, a fragment lead (13, K-D = 51 mu M) was elaborated into a potent NAMPT inhibitor (39, NAMPT IC50 = 0.0051 mu M, A2780 cell culture IC50 = 0.000 49 mu M) which demonstrated encouraging in vivo efficacy in an HT-1080 mouse xenograft tumor model.

  DOI：

  10.1021/jm4015108