5-bromo-2-chloro-4-(2-ethoxyphenoxy)pyrimidine | 884603-58-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-bromo-2-chloro-4-(2-ethoxyphenoxy)pyrimidine
• 英文别名: 5-Bromo-2-chloro-4-(2-ethoxyphenoxy)pyrimidine
• CAS: 884603-58-1
• 化学式: C₁₂H₁₀BrClN₂O₂
• 分子量: 329.581
• InChiKey: AHOMGTGIYWGUNV-UHFFFAOYSA-N

物化性质

• 沸点：
  421.2±35.0 °C(Predicted)
• 密度：
  1.532±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-bromo-2-chloro-4-(2-ethoxyphenoxy)pyrimidine 、 3-甲基苯胺 在 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 以81%的产率得到5-bromo-4-(2-ethoxyphenoxy)-N-(m-tolyl)pyrimidin-2-amine
  参考文献：
  名称：

  Discovery of 5-bromo-4-phenoxy-N-phenylpyrimidin-2-amine derivatives as novel ULK1 inhibitors that block autophagy and induce apoptosis in non-small cell lung cancer

  摘要：

  UNC51-like kinase1 (ULK1) recruits its binding partners and initiates the autophagy process in cancer. ULK1 is significantly overexpressed in Non-small cell lung cancer (NSCLC) and negatively correlated with clinical prognosis in NSCLC patients. Based upon the binding features of ULK1, we explored the pharmacophore modeling to discover the common anchoring features. It was verified by synthesizing 5-bromo-4-phenoxy-N-phenylpyrimidin-2-amine derivatives, as well as subsequently elucidating the structure-activity relationships (SAR). Among all the obtained ULK1 inhibitors, 5-bromo-4-(2-fluoro-4-nitrophenoxy)-N-(3,4,5-trimethoxyphenyl) pyrimidin-2-amine (3s), was the most active one. The docking analysis was conducted to compare 3s and SBI-0206965, which further elucidated the roles of the H-bond donor. This compound inhibited the proliferation of A549 cells and showed strong inhibitory activity against ULK1 kinase. Moreover, we found that compound 3s could induce apoptosis while simultaneously blocking autophagy. Collectively, these findings shed new light on compound 3s that would be utilized as a promising candidate drug for the future NSCLC therapy.

  DOI：

  10.1016/j.ejmech.2020.112782
• 作为产物：
  描述：

  邻乙氧基苯酚 、 5-溴-2,4-二氯嘧啶 在 N,N-二异丙基乙胺 作用下， 以 乙醇 为溶剂， 生成 5-bromo-2-chloro-4-(2-ethoxyphenoxy)pyrimidine
  参考文献：
  名称：

  Discovery of 5-bromo-4-phenoxy-N-phenylpyrimidin-2-amine derivatives as novel ULK1 inhibitors that block autophagy and induce apoptosis in non-small cell lung cancer

  摘要：

  UNC51-like kinase1 (ULK1) recruits its binding partners and initiates the autophagy process in cancer. ULK1 is significantly overexpressed in Non-small cell lung cancer (NSCLC) and negatively correlated with clinical prognosis in NSCLC patients. Based upon the binding features of ULK1, we explored the pharmacophore modeling to discover the common anchoring features. It was verified by synthesizing 5-bromo-4-phenoxy-N-phenylpyrimidin-2-amine derivatives, as well as subsequently elucidating the structure-activity relationships (SAR). Among all the obtained ULK1 inhibitors, 5-bromo-4-(2-fluoro-4-nitrophenoxy)-N-(3,4,5-trimethoxyphenyl) pyrimidin-2-amine (3s), was the most active one. The docking analysis was conducted to compare 3s and SBI-0206965, which further elucidated the roles of the H-bond donor. This compound inhibited the proliferation of A549 cells and showed strong inhibitory activity against ULK1 kinase. Moreover, we found that compound 3s could induce apoptosis while simultaneously blocking autophagy. Collectively, these findings shed new light on compound 3s that would be utilized as a promising candidate drug for the future NSCLC therapy.

  DOI：

  10.1016/j.ejmech.2020.112782

文献信息

• Heteroaryl-substituted alkyne compounds and method of use
  申请人：Chaffee C. Stuart

  公开号：US20060217380A1

  公开（公告）日：2006-09-28

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I wherein A 1 , A 2 , A 3 , A 4 , R 1 and R 2 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.

  本发明涉及一种新型化合物类别，可用于预防和治疗蛋白激酶介导的疾病，包括炎症、癌症和相关病症。该化合物具有一般式I，其中A1、A2、A3、A4、R1和R2如本文所定义。因此，本发明还涉及包含本发明化合物的制药组合物，使用本发明化合物和组合物预防和治疗激酶介导的疾病的方法，以及用于制备本发明化合物的中间体和过程。
• HETEROARYL-SUBSTITUTED ALKYNE COMPOUNDS AND METHOD OF USE
  申请人：Chaffee Stuart C.

  公开号：US20100160283A1

  公开（公告）日：2010-06-24

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I wherein A 1 , A 2 , A 3 , A 4 , R 1 and R 2 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.

  本发明涉及一类新的化合物，用于预防和治疗蛋白激酶介导的疾病，包括炎症、癌症和相关疾病。该化合物具有一般式I，其中A1、A2、A3、A4、R1和R2的定义如本文所述。因此，本发明还涉及包括本发明化合物的制药组合物，使用本发明化合物和组合物预防和治疗激酶介导的疾病的方法，以及用于制备本发明化合物的中间体和过程。
• WO2006/44823
  申请人：——

  公开号：——

  公开（公告）日：——
• US7776869B2
  申请人：——

  公开号：US7776869B2

  公开（公告）日：2010-08-17
• US8557996B2
  申请人：——

  公开号：US8557996B2

  公开（公告）日：2013-10-15