1-[4-[[(2-chloroquinazolin-4-yl)amino]methyl]benzoyl]-N-(4-fluorobenzyl)piperidine-4-carboxamide | 1356125-08-0

• 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: 1-[4-[[(2-chloroquinazolin-4-yl)amino]methyl]benzoyl]-N-(4-fluorobenzyl)piperidine-4-carboxamide
• 英文别名: 1-[4-[[(2-chloroquinazolin-4-yl)amino]methyl]benzoyl]-N-[(4-fluorophenyl)methyl]piperidine-4-carboxamide
• CAS: 1356125-08-0
• 化学式: C₂₉H₂₇ClFN₅O₂
• 分子量: 532.017
• InChiKey: XUXOMJHIXJSWET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  87.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  正丙胺 、 1-[4-[[(2-chloroquinazolin-4-yl)amino]methyl]benzoyl]-N-(4-fluorobenzyl)piperidine-4-carboxamide 以160 mg的产率得到1-[4-[[(2-(propylamino)quinazolin-4-yl)amino]methyl]benzoyl]-N-(4-fluorobenzyl)piperidine-4-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of New Diaminoquinazolines as β-Catenin/Tcf4 Pathway Inhibitors

  摘要：

  More than 50 new diaminoquinazoline derivatives have been synthesized and evaluated in a colon carcinoma cell growth inhibition assay using HCT116 and SW480 cells. Twenty compounds with good cell growth inhibitory activities (<4 mu M) were tested as inhibitors of the beta-catenin/T cell transcription factor 4 (Tcf4) signaling pathway using a HCT116 cell-based luciferase reporter assay. Results from the biological activities as well as the comparative molecular field analysis (CoMFA) of the properties of the molecules yielded a preliminary structure-activity relationship (SAR). Three potent compounds, 74, 78, and 86, showed IC50 values <1 mu M for growth inhibition of HCT116 cells and similar to 1 mu M for SW480 cells, as well as IC50 values of 1.5-2.5 mu M for HCT116 cells with the luciferase reporter assay.

  DOI：

  10.1021/jm201494a
• 作为产物：
  描述：

  1-Boc-4-哌啶甲酸 在 1-羟基苯并三唑 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 14.0h， 生成 1-[4-[[(2-chloroquinazolin-4-yl)amino]methyl]benzoyl]-N-(4-fluorobenzyl)piperidine-4-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of New Diaminoquinazolines as β-Catenin/Tcf4 Pathway Inhibitors

  摘要：

  More than 50 new diaminoquinazoline derivatives have been synthesized and evaluated in a colon carcinoma cell growth inhibition assay using HCT116 and SW480 cells. Twenty compounds with good cell growth inhibitory activities (<4 mu M) were tested as inhibitors of the beta-catenin/T cell transcription factor 4 (Tcf4) signaling pathway using a HCT116 cell-based luciferase reporter assay. Results from the biological activities as well as the comparative molecular field analysis (CoMFA) of the properties of the molecules yielded a preliminary structure-activity relationship (SAR). Three potent compounds, 74, 78, and 86, showed IC50 values <1 mu M for growth inhibition of HCT116 cells and similar to 1 mu M for SW480 cells, as well as IC50 values of 1.5-2.5 mu M for HCT116 cells with the luciferase reporter assay.

  DOI：

  10.1021/jm201494a

文献信息

• Design, Synthesis, and Biological Evaluation of New Diaminoquinazolines as β-Catenin/Tcf4 Pathway Inhibitors
  作者：Yongjun Mao、Nan Lin、Wang Tian、Xiaofeng Han、Xiaobing Han、Ziwei Huang、Jing An

  DOI：10.1021/jm201494a

  日期：2012.2.9

  More than 50 new diaminoquinazoline derivatives have been synthesized and evaluated in a colon carcinoma cell growth inhibition assay using HCT116 and SW480 cells. Twenty compounds with good cell growth inhibitory activities (<4 mu M) were tested as inhibitors of the beta-catenin/T cell transcription factor 4 (Tcf4) signaling pathway using a HCT116 cell-based luciferase reporter assay. Results from the biological activities as well as the comparative molecular field analysis (CoMFA) of the properties of the molecules yielded a preliminary structure-activity relationship (SAR). Three potent compounds, 74, 78, and 86, showed IC50 values <1 mu M for growth inhibition of HCT116 cells and similar to 1 mu M for SW480 cells, as well as IC50 values of 1.5-2.5 mu M for HCT116 cells with the luciferase reporter assay.