N-(9,9-difluoro-9H-fluoren-2-yl)-2-(2',3-dimethyl[2,4'-bipyridin]-5-yl)acetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-(9,9-difluoro-9H-fluoren-2-yl)-2-(2',3-dimethyl[2,4'-bipyridin]-5-yl)acetamide
• 英文别名: N-(9,9-difluorofluoren-2-yl)-2-[5-methyl-6-(2-methylpyridin-4-yl)pyridin-3-yl]acetamide
• 化学式: C₂₇H₂₁F₂N₃O
• 分子量: 441.48
• InChiKey: VBZOGWJGPSQBDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  54.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-甲基-2-丁烯腈 在 sodium tetrahydroborate 、 四(三苯基膦)钯 、 氯化亚砜 、 硫酸 、 水 、 potassium carbonate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 potassium iodide 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 59.0h， 生成 N-(9,9-difluoro-9H-fluoren-2-yl)-2-(2',3-dimethyl[2,4'-bipyridin]-5-yl)acetamide
  参考文献：
  名称：

  Design, synthesis, and evaluation of potent Wnt signaling inhibitors featuring a fused 3-ring system

  摘要：

  The Wnt signaling pathway is a critical developmental pathway which operates through control of cellular functions such as proliferation and differentiation. Aberrant Wnt signaling has been linked to the formation and metastasis of tumors. Porcupine, a member of the membrane -bound O-acyltransferase family of proteins, is an important component of the Wnt pathway. Porcupine catalyzes the palmitoylation of Wnt proteins, a process needed for their secretion and activity. Here we report a novel series of compounds obtained by a scaffold hybridization strategy from a known porcupine inhibitor class. The leading compound 59 demonstrated subnanomolar inhibition of Wnt signaling in a paracrine cellular assay. Compound 59 also showed excellent chemical, plasma and liver microsomal stabilities. Furthermore, compound 59 exhibited good pharmacokinetic profiles with 30% oral bioavailability in rat. Collectively, these results strongly support further optimization of this novel scaffold to develop better Wnt pathway inhibitors. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.026

文献信息

• Design, synthesis, and evaluation of potent Wnt signaling inhibitors featuring a fused 3-ring system
  作者：Zhixiang Xu、Jiajun Li、Yiyuan Wu、Zhijian Sun、Lusong Luo、Zhilin Hu、Sudan He、Jiyue Zheng、Hongjian Zhang、Xiaohu Zhang

  DOI：10.1016/j.ejmech.2015.11.026

  日期：2016.1

  The Wnt signaling pathway is a critical developmental pathway which operates through control of cellular functions such as proliferation and differentiation. Aberrant Wnt signaling has been linked to the formation and metastasis of tumors. Porcupine, a member of the membrane -bound O-acyltransferase family of proteins, is an important component of the Wnt pathway. Porcupine catalyzes the palmitoylation of Wnt proteins, a process needed for their secretion and activity. Here we report a novel series of compounds obtained by a scaffold hybridization strategy from a known porcupine inhibitor class. The leading compound 59 demonstrated subnanomolar inhibition of Wnt signaling in a paracrine cellular assay. Compound 59 also showed excellent chemical, plasma and liver microsomal stabilities. Furthermore, compound 59 exhibited good pharmacokinetic profiles with 30% oral bioavailability in rat. Collectively, these results strongly support further optimization of this novel scaffold to develop better Wnt pathway inhibitors. (C) 2015 Elsevier Masson SAS. All rights reserved.