1-(4-(2-(4-fluorobenzylamino)-5-(3-methylisoxazol-5-yl)pyrimidin-4-yl)piperidin-1-yl)ethanone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(4-(2-(4-fluorobenzylamino)-5-(3-methylisoxazol-5-yl)pyrimidin-4-yl)piperidin-1-yl)ethanone
• 英文别名: 1-[4-[2-[(4-Fluorophenyl)methylamino]-5-(3-methyl-1,2-oxazol-5-yl)pyrimidin-4-yl]piperidin-1-yl]ethanone；1-[4-[2-[(4-fluorophenyl)methylamino]-5-(3-methyl-1,2-oxazol-5-yl)pyrimidin-4-yl]piperidin-1-yl]ethanone
• 化学式: C₂₂H₂₄FN₅O₂
• 分子量: 409.463
• InChiKey: VVRBHVWQAHQJMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3,5-二甲基异唑 在 盐酸 、 sodium methylate 、 三乙胺 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 正己烷 、 二氯甲烷 、 氯仿 、 乙腈 、 苯 为溶剂， 反应 66.0h， 生成 1-(4-(2-(4-fluorobenzylamino)-5-(3-methylisoxazol-5-yl)pyrimidin-4-yl)piperidin-1-yl)ethanone
  参考文献：
  名称：

  Identification of 2-aminopyrimidine derivatives as inhibitors of the canonical Wnt signaling pathway

  摘要：

  The canonical Wnt signaling pathway plays a fundamental role in embryonic as well as in adult development. Consequently, dysregulation of the pathway has been linked to a wide spectrum of pathological conditions. In a program aimed at the identification of small molecule inhibitors of the canonical Wnt pathway we identified a series of 2-aminopyrimidine derivatives which specifically inhibited the pathway with minimal or no sign of cellular toxicity. The hit molecules 1 and 2 showed promising inhibitory activity with IC50 values of approximately 10 mu M, but low solubility and metabolic stability. During the early stage of the hit series exploration, the pyrimidine core was variously decorated to obtain active compounds with a better physico-chemical profile. In particular, compound 13 showed Wnt inhibition activity comparable to hit molecules 1 and 2, with improved physico-chemical properties. Therefore, this series of compounds may be considered a promising starting point for the design of novel small molecule inhibitors of the canonical Wnt pathway. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.015

文献信息

• Identification of 2-aminopyrimidine derivatives as inhibitors of the canonical Wnt signaling pathway
  作者：Fabio Del Bello、Aniket Farande、Mario Giannella、Alessandro Piergentili、Wilma Quaglia、Tiziana Benicchi、Federico Cappelli、Arianna Nencini、Massimiliano Salerno、Russell J. Thomas、Massimilano Travagli、Maurizio Varrone

  DOI：10.1016/j.bmc.2015.07.015

  日期：2015.9

  The canonical Wnt signaling pathway plays a fundamental role in embryonic as well as in adult development. Consequently, dysregulation of the pathway has been linked to a wide spectrum of pathological conditions. In a program aimed at the identification of small molecule inhibitors of the canonical Wnt pathway we identified a series of 2-aminopyrimidine derivatives which specifically inhibited the pathway with minimal or no sign of cellular toxicity. The hit molecules 1 and 2 showed promising inhibitory activity with IC50 values of approximately 10 mu M, but low solubility and metabolic stability. During the early stage of the hit series exploration, the pyrimidine core was variously decorated to obtain active compounds with a better physico-chemical profile. In particular, compound 13 showed Wnt inhibition activity comparable to hit molecules 1 and 2, with improved physico-chemical properties. Therefore, this series of compounds may be considered a promising starting point for the design of novel small molecule inhibitors of the canonical Wnt pathway. (C) 2015 Elsevier Ltd. All rights reserved.