trans-2-phenyl-N-(pyridin-4-yl)cyclopropanecarboxamide | 494842-46-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: trans-2-phenyl-N-(pyridin-4-yl)cyclopropanecarboxamide
• 英文别名: 2-phenyl-N-4-pyridinylcyclopropanecarboxamide；2-phenyl-N-pyridin-4-ylcyclopropane-1-carboxamide
• CAS: 494842-46-5
• 化学式: C₁₅H₁₄N₂O
• mdl: MFCD01920512
• 分子量: 238.289
• InChiKey: NOMFGVQIYPJHNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-氨基吡啶 、 2-苯基环丙烷羧酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以6%的产率得到trans-2-phenyl-N-(pyridin-4-yl)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

文献信息

• Fragment-Based Identification of Amides Derived from <i>trans</i>-2-(Pyridin-3-yl)cyclopropanecarboxylic Acid as Potent Inhibitors of Human Nicotinamide Phosphoribosyltransferase (NAMPT)
  作者：Anthony M. Giannetti、Xiaozhang Zheng、Nicholas J. Skelton、Weiru Wang、Brandon J. Bravo、Kenneth W. Bair、Timm Baumeister、Eric Cheng、Lisa Crocker、Yezhen Feng、Janet Gunzner-Toste、Yen-Ching Ho、Rongbao Hua、Bianca M. Liederer、Yongbo Liu、Xiaolei Ma、Thomas O’Brien、Jason Oeh、Deepak Sampath、Youming Shen、Chengcheng Wang、Leslie Wang、Hongxing Wu、Yang Xiao、Po-wai Yuen、Mark Zak、Guiling Zhao、Qiang Zhao、Peter S. Dragovich

  DOI：10.1021/jm4015108

  日期：2014.2.13

  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.