4-{2-[4-(4-fluorophenyl)piperazin-1-yl]ethoxy}-benzaldehyde | 1616110-81-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-{2-[4-(4-fluorophenyl)piperazin-1-yl]ethoxy}-benzaldehyde
• 英文别名: 4-{2-[4-(4-Fluorophenyl)piperazin-1-yl]ethoxy}benzaldehyde；4-[2-[4-(4-fluorophenyl)piperazin-1-yl]ethoxy]benzaldehyde
• CAS: 1616110-81-6
• 化学式: C₁₉H₂₁FN₂O₂
• 分子量: 328.386
• InChiKey: ADHQLOWDLJFORL-UHFFFAOYSA-N

物化性质

• 沸点：
  494.0±45.0 °C(Predicted)
• 密度：
  1.195±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.84
• 重原子数：
  24.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  32.78
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  7-苯并呋喃甲酰胺2,3-二氢-3氧代 、 4-{2-[4-(4-fluorophenyl)piperazin-1-yl]ethoxy}-benzaldehyde 在 ammonium acetate 作用下， 以 甲苯 为溶剂， 反应 8.0h， 以58%的产率得到(Z)-2-(4-{2-[4-(4-fluorophenyl)piperazin-1-yl]-ethoxy}benzylidene)-3-oxo-2,3-dihydrobenzofuran-7-carboxamide
  参考文献：
  名称：

  Discovery and Structure–Activity Relationship of Novel 2,3-Dihydrobenzofuran-7-carboxamide and 2,3-Dihydrobenzofuran-3(2H)-one-7-carboxamide Derivatives as Poly(ADP-ribose)polymerase-1 Inhibitors

  摘要：

  Novel substituted 2,3-dihydrobenzofuran-7-carboxamide (DHBF-7-carboxamide) and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide (DHBF-3-one-7-carboxamide) derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy resulted in lead compound 3 (DHBF-7-carboxamide; IC50 = 9.45 mu M). To facilitate synthetically feasible derivatives, an alternative core was designed, DHBF-3-one-7-carboxamide (36, IC50 = 16.2 mu M). The electrophilic 2-position of this scaffold was accessible for extended modifications. Substituted benzylidene derivatives at the 2-position were found to be the most potent, with 3',4'-dihydroxybenzylidene 58 (IC50 = 0.531 mu M) showing a 30-fold improvement in potency. Various heterocycles attached at the 4'-hydroxyl/4'-amino of the benzylidene moiety resulted in significant improvement in inhibition of PARP-1 activity (e.g., compounds 66-68, 70, 72, and 73; IC50 values from 0.718 to 0.079 mu M). Compound 66 showed selective cytotoxicity in BRCA2-deficient DT40 cells. Crystal structures of three inhibitors (compounds (-)-13c, 59, and 65) bound to a multidomain PARP-1 structure were obtained, providing insights into further development of these inhibitors.

  DOI：

  10.1021/jm5002502
• 作为产物：
  描述：

  对羟基苯甲醛 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 18.0h， 生成 4-{2-[4-(4-fluorophenyl)piperazin-1-yl]ethoxy}-benzaldehyde
  参考文献：
  名称：

  Discovery and Structure–Activity Relationship of Novel 2,3-Dihydrobenzofuran-7-carboxamide and 2,3-Dihydrobenzofuran-3(2H)-one-7-carboxamide Derivatives as Poly(ADP-ribose)polymerase-1 Inhibitors

  摘要：

  Novel substituted 2,3-dihydrobenzofuran-7-carboxamide (DHBF-7-carboxamide) and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide (DHBF-3-one-7-carboxamide) derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy resulted in lead compound 3 (DHBF-7-carboxamide; IC50 = 9.45 mu M). To facilitate synthetically feasible derivatives, an alternative core was designed, DHBF-3-one-7-carboxamide (36, IC50 = 16.2 mu M). The electrophilic 2-position of this scaffold was accessible for extended modifications. Substituted benzylidene derivatives at the 2-position were found to be the most potent, with 3',4'-dihydroxybenzylidene 58 (IC50 = 0.531 mu M) showing a 30-fold improvement in potency. Various heterocycles attached at the 4'-hydroxyl/4'-amino of the benzylidene moiety resulted in significant improvement in inhibition of PARP-1 activity (e.g., compounds 66-68, 70, 72, and 73; IC50 values from 0.718 to 0.079 mu M). Compound 66 showed selective cytotoxicity in BRCA2-deficient DT40 cells. Crystal structures of three inhibitors (compounds (-)-13c, 59, and 65) bound to a multidomain PARP-1 structure were obtained, providing insights into further development of these inhibitors.

  DOI：

  10.1021/jm5002502