6-(4-溴-苯基)-4-氯-呋喃并[2,3-d]嘧啶 | 887592-53-2

• 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
• 中文名称: 6-(4-溴-苯基)-4-氯-呋喃并[2,3-d]嘧啶
• 英文名称: 6-(4-bromophenyl)-4-chlorofuro[2,3-d]pyrimidine
• CAS: 887592-53-2
• 化学式: C₁₂H₆BrClN₂O
• 分子量: 309.549
• InChiKey: VTVXSAJCMNXOGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(4-溴-苯基)-4-氯-呋喃并[2,3-d]嘧啶 在 2-(二环己基膦)3,6-二甲氧基-2′,4′,6′-三异丙基-1,1′-联苯 、 Brettphos palladacycle 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 正丁醇 为溶剂， 反应 2.0h， 生成 (R)-N-(1-phenylethyl)-6-(4-((2-(piperidin-1-yl)ethyl) amino)phenyl)furo[2,3-d]pyrimidin-4-amine
  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
• 作为产物：
  描述：

  2-氨基-5-(4-溴苯基)-3-呋喃甲腈 在 甲酸 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 6-(4-溴-苯基)-4-氯-呋喃并[2,3-d]嘧啶
  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

• Identification of fused pyrimidines as interleukin 17 secretion inhibitors
  作者：Ann Christin Reiersølmoen、Jin Han、Eirik Sundby、Bård Helge Hoff

  DOI：10.1016/j.ejmech.2018.06.019

  日期：2018.7

  Inhibiting the interleukin 17 pathway is of interest in a number of autoimmune diseases. Herein, 42 fused pyrimidines have been evaluated as interleukin 17 secretion inhibitors using a phenotypic assay with peripheral blood mononuclear cells. 7H-Pyrrolo [2,3-d]pyrimidin-4-amines having aryl groups at C-S or C-6 were found more active than the corresponding thieno- and furopyrimidines. Low cytotoxicity was seen for the most active inhibitors. However, the pyrrolopyrimidines also inhibit interleukin 5 secretion, suggesting that selective interleukin 17 inhibitors should rather be based on furopyrimidines. Profiling towards a panel of 51 kinases and assays towards the retinoic acid receptor-related orphan receptor gamma were performed in order to identify the compounds mode of action. (C) 2018 Elsevier Masson SAS. All rights reserved.
• 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.