N-((9H-fluoren-2-yl)methyl)-[1,1'-biphenyl]-4-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-((9H-fluoren-2-yl)methyl)-[1,1'-biphenyl]-4-carboxamide
• 英文别名: N-(9H-fluoren-2-ylmethyl)-4-phenylbenzamide
• 化学式: C₂₇H₂₁NO
• 分子量: 375.47
• InChiKey: JLYUMHPSBGZNRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  9H-芴-2-甲腈 在 盐酸 、 palladium on activated charcoal 、 氢气 、 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 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 N-((9H-fluoren-2-yl)methyl)-[1,1'-biphenyl]-4-carboxamide
  参考文献：
  名称：

  Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the ‘reversed’ amide scaffold

  摘要：

  The Wnt signaling pathway is an essential signal transduction pathway which leads to the regulation of cellular processes such as proliferation, differentiation and migration. Aberrant Wnt signaling is known to have an association with multiple cancers. Porcupine is an enzyme that catalyses the addition of palmitoleate to a serine residue in Wnt proteins, a process which is required for the secretion of Wnt proteins. Here we report the synthesis and structure-activity-relationship of the novel porcupine inhibitors based on a 'reversed' amide scaffold. The leading compound 53 was as potent as the clinical compound LGK974 in a cell based STF reporter gene assay. Compound 53 potently inhibited the secretion of Wnt3A, therefore was confirmed to be a porcupine inhibitor. Furthermore, compound 53 showed excellent chemical and plasma stabilities. However, the clearance of compound 53 in liver microsomal tests was moderate to high, and the solubility of compound 53 was suboptimal. Collective efforts toward further optimization of this novel tricyclic template to develop better porcupine inhibitors will be subsequently undertaken and reported in due course. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.09.041

文献信息

• Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the ‘reversed’ amide scaffold
  作者：Zhixiang Xu、Xiangxiang Xu、Ruadhan O’Laoi、Haikuo Ma、Jiyue Zheng、Shuaishuai Chen、Lusong Luo、Zhilin Hu、Sudan He、Jiajun Li、Hongjian Zhang、Xiaohu Zhang

  DOI：10.1016/j.bmc.2016.09.041

  日期：2016.11

  The Wnt signaling pathway is an essential signal transduction pathway which leads to the regulation of cellular processes such as proliferation, differentiation and migration. Aberrant Wnt signaling is known to have an association with multiple cancers. Porcupine is an enzyme that catalyses the addition of palmitoleate to a serine residue in Wnt proteins, a process which is required for the secretion of Wnt proteins. Here we report the synthesis and structure-activity-relationship of the novel porcupine inhibitors based on a 'reversed' amide scaffold. The leading compound 53 was as potent as the clinical compound LGK974 in a cell based STF reporter gene assay. Compound 53 potently inhibited the secretion of Wnt3A, therefore was confirmed to be a porcupine inhibitor. Furthermore, compound 53 showed excellent chemical and plasma stabilities. However, the clearance of compound 53 in liver microsomal tests was moderate to high, and the solubility of compound 53 was suboptimal. Collective efforts toward further optimization of this novel tricyclic template to develop better porcupine inhibitors will be subsequently undertaken and reported in due course. (C) 2016 Elsevier Ltd. All rights reserved.