N-[4-[[(2-chloroquinazolin-4-yl)amino]methyl]phenyl]-4-fluorobenzamide | 1039735-65-3

• 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: N-[4-[[(2-chloroquinazolin-4-yl)amino]methyl]phenyl]-4-fluorobenzamide
• 英文别名: N-(4-{[(2-chloroquinazolin-4-yl)amino]methyl}phenyl)-4-fluorobenzamide
• CAS: 1039735-65-3
• 化学式: C₂₂H₁₆ClFN₄O
• 分子量: 406.847
• InChiKey: SDKHXHHHWOIAGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  66.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[4-[[(2-chloroquinazolin-4-yl)amino]methyl]phenyl]-4-fluorobenzamide 、 二甲胺 在 二氯甲烷 、 甲醇 作用下， 以 四氢呋喃 为溶剂， 反应 21.0h， 以to give off-white solid (96 mg, yield: 93%)的产率得到4-fluoro-N-[4-[[(2-(dimethylamino)quinazolin-4-yl)amino]methyl]phenyl]benzamide
  参考文献：
  名称：

  AMINO-SUBSTITUTED QUINAZOLINE DERIVATIVES AS INHIBITORS OF BETA-CATENIN/TCF-4 PATHWAY AND CANCER TREATMENT AGENTS

  摘要：

  本发明涉及氨基取代的喹唑啉衍生物，作为β-连环蛋白/TCF-4途径的抑制剂，可用于癌症治疗；涉及其制备方法；涉及包含它们的制药组合物；以及使用它们的方法。

  公开号：

  US20090004185A1
• 作为产物：
  描述：

  对氟苯甲酰氯 在 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 N-[4-[[(2-chloroquinazolin-4-yl)amino]methyl]phenyl]-4-fluorobenzamide
  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

• WO2008/86462
  申请人：——

  公开号：——

  公开（公告）日：——
• Design and Synthesis of Novel Diaminoquinazolines with <i>in Vivo</i> Efficacy for β-Catenin/T-Cell Transcriptional Factor 4 Pathway Inhibition
  作者：Christoph M. Dehnhardt、Aranapakam M. Venkatesan、Zecheng Chen、Semiramis Ayral-Kaloustian、Osvaldo Dos Santos、Efren Delos Santos、Kevin Curran、Max T. Follettie、Veronica Diesl、Judy Lucas、Yi Geng、Susan Quinn DeJoy、Rosanne Petersen、Inder Chaudhary、Natasja Brooijmans、Tarek S. Mansour、Kim Arndt、Lei Chen

  DOI：10.1021/jm901370m

  日期：2010.1.28

  We are introducing a novel series of 2,4-diaminoquinazolines as beta-catenin/Tcf4 inhibitors which were identified by ligand-based design. Here we elucidate the SAR of this series and explain how we were able to improve key Molecular properties such as Solubility and cLogP leading to compound 9. Analogue 9 exhibited better biological activity and improved physical and pharmacological properties relative to the HTS hit 49. Furthermore, 9 demonstrated good cell growth inhibition against several human colorectal cancer lines such as LoVo and HT29. In addition, treatment with compound 9 led to gene expression changes that overlapped significantly with the transcriptional profile resulting from the pathway inhibition by siRNA knockdown of beta-catenin or Tcf4. Subsequently, 9 was tested for efficacy in a beta-catenin/RKE-mouse xenograft, where it led to more then 50% decrease in tumor Volume.
• [EN] AMINO-SUBSTITUTED QUINAZOLINE DERIVATIVES AS INHIBITORS OF ß-CANTENIN/TCF-4 PATHWAY AND CANCER TREATMENT AGENTS<br/>[FR] DÉRIVÉS DE QUINALOZINE SUBSTITUÉS PAR AMINO EN TANT QU'INHIBITEURS DE LA VOIE B-CATÉNINE/TCF-4 ET AGENTS DE TRAITEMENT DU CANCER
  申请人：WYETH CORP

  公开号：WO2008086462A2

  公开（公告）日：2008-07-17

  [EN] The present invention relates to amino-substituted quinazoline derivatives as inhibitors of ß-catenin/tcf-4 pathway, which can be useful in the treatment of cancer; to processes for their preparation; to pharmaceutical compositions comprising them; and to methods of using them.
  [FR] L'invention concerne des dérivés de quinazoline substitués par amino en tant qu'inhibiteurs de voie b-caténine/TCF-4, qui peuvent être utiles dans le traitement du cancer ; des procédés pour leur préparation ; des compositions pharmaceutiques les renfermant ; et des procédés d'utilisation de ceux-ci.
• 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.
• AMINO-SUBSTITUTED QUINAZOLINE DERIVATIVES AS INHIBITORS OF BETA-CATENIN/TCF-4 PATHWAY AND CANCER TREATMENT AGENTS
  申请人：VENKATESAN Aranapakam M.

  公开号：US20090004185A1

  公开（公告）日：2009-01-01

  The present invention relates to amino-substituted quinazoline derivatives as inhibitors of β-catenin/tcf-4 pathway, which can be useful in the treatment of cancer; to processes for their preparation; to pharmaceutical compositions comprising them; and to methods of using them.

  本发明涉及氨基取代的喹唑啉衍生物，作为β-连环蛋白/TCF-4途径的抑制剂，可用于癌症治疗；涉及其制备方法；涉及包含它们的制药组合物；以及使用它们的方法。