(S)-2-phenyl-2-((6-phenylfuro[2,3-d]pyrimidin-4-yl)amino)ethanol | 1226548-50-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃[2,3-d]嘧啶
• 英文名称: (S)-2-phenyl-2-((6-phenylfuro[2,3-d]pyrimidin-4-yl)amino)ethanol
• 英文别名: (2S)-2-phenyl-2-[(6-phenylfuro[2,3-d]pyrimidin-4-yl)amino]ethanol
• CAS: 1226548-50-0
• 化学式: C₂₀H₁₇N₃O₂
• 分子量: 331.374
• InChiKey: GPERDLZLRGFVOX-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  71.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基-5-苯基-3-呋喃甲腈 在 甲酸 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 24.0h， 生成 (S)-2-phenyl-2-((6-phenylfuro[2,3-d]pyrimidin-4-yl)amino)ethanol
  参考文献：
  名称：

  Chiral 6-aryl-furo[2,3-d]pyrimidin-4-amines as EGFR inhibitors

  摘要：

  Epidermal growth factor receptor inhibitors are of importance in cancer therapy and possibly in the management of pain. Herein, we report a structure-activity relationship study with 29 new 6-aryl-furo [2,3-d]pyrimidin-4-amines, involving modification of the 4-amino group and 6-aryl function. The EGFR activity was especially dependent on having a chiral 4-benzylamino group with correct stereochemistry. Molecular dynamics indicate this to be due to favourable cation-pi interactions. The most active inhibitor identified, equipotent to Erlotinib, was substituted with (R)-1-phenylethylamine at C-4 and a N-1, N-1-dimethyl-1,2-diamine group in para position of the 6-aryl moiety. These new furopyrimidines had a different off-target kinase profile when compared to Erlotinib, and also possessed high activity towards Ba/F3 EGFR(L858R) reporter cells. Further, comparing the EGFR data of the furo[2,3-d]pyrimidin-4-amines with that of the corresponding thieno- and pyrrolopyrimidines concludes the furopyrimidine scaffold to be highly useful for development of new epidermal growth factor receptor antagonists. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.04.054

文献信息

• Fused Bicyclic and Tricyclic Pyrimidine Compounds as Tyrosine Kinase Inhibitors
  申请人：Hsieh Hsing-Pang

  公开号：US20100120805A1

  公开（公告）日：2010-05-13

  Fused bicyclic or tricyclic compounds of formula (I): wherein A, B, C, X, Y, m, and n are defined herein. Also disclosed are a method for inhibiting EGFR kinase activity and a method for treating cancer with these compounds.

  式(I)的融合双环或三环化合物： 其中A、B、C、X、Y、m和n在此处定义。还公开了一种抑制EGFR激酶活性的方法以及使用这些化合物治疗癌症的方法。
• US8507502B2
  申请人：——

  公开号：US8507502B2

  公开（公告）日：2013-08-13
• [EN] FUSED BICYCLIC AND TRICYCLIC PYRIMIDINE COMPOUNDS AS TYROSINE KINASE INHIBITORS<br/>[FR] COMPOSÉS DE PYRIMIDINE BICYCLIQUES ET TRICYCLIQUES CONDENSÉS À TITRE D'INHIBITEURS DE TYROSINE KINASE
  申请人：NAT HEALTH RESEARCH INSTITUTES

  公开号：WO2010054285A2

  公开（公告）日：2010-05-14

  Fused bicyclic or tricyclic compounds of formula (I) defined herein are disclosed. Also disclosed are a method for inhibiting EGFR kinase activity and a method for treating cancer with these compounds.
• Chiral 6-aryl-furo[2,3-d]pyrimidin-4-amines as EGFR inhibitors
  作者：Jin Han、Svein Jacob Kaspersen、Sondre Nervik、Kristin G. Nørsett、Eirik Sundby、Bård Helge Hoff

  DOI：10.1016/j.ejmech.2016.04.054

  日期：2016.8

  Epidermal growth factor receptor inhibitors are of importance in cancer therapy and possibly in the management of pain. Herein, we report a structure-activity relationship study with 29 new 6-aryl-furo [2,3-d]pyrimidin-4-amines, involving modification of the 4-amino group and 6-aryl function. The EGFR activity was especially dependent on having a chiral 4-benzylamino group with correct stereochemistry. Molecular dynamics indicate this to be due to favourable cation-pi interactions. The most active inhibitor identified, equipotent to Erlotinib, was substituted with (R)-1-phenylethylamine at C-4 and a N-1, N-1-dimethyl-1,2-diamine group in para position of the 6-aryl moiety. These new furopyrimidines had a different off-target kinase profile when compared to Erlotinib, and also possessed high activity towards Ba/F3 EGFR(L858R) reporter cells. Further, comparing the EGFR data of the furo[2,3-d]pyrimidin-4-amines with that of the corresponding thieno- and pyrrolopyrimidines concludes the furopyrimidine scaffold to be highly useful for development of new epidermal growth factor receptor antagonists. (C) 2016 Elsevier Masson SAS. All rights reserved.