2-(4-哌嗪-1-苯基)-苯并噁唑 | 885275-02-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 2-(4-哌嗪-1-苯基)-苯并噁唑
• 中文别名: 金石蚕苷；2-(4-(哌嗪-1-基)苯基)苯并[D]恶唑
• 英文名称: 2-(4-(piperazin-1-yl)phenyl)benzo[d]oxazole
• 英文别名: 2-(4-Piperazin-1-YL-phenyl)-benzooxazole；2-(4-piperazin-1-ylphenyl)-1,3-benzoxazole
• CAS: 885275-02-5
• 化学式: C₁₇H₁₇N₃O
• 分子量: 279.341
• InChiKey: LCMNDMOKEJXAOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  41.3
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  5-甲基呋喃醛 、 2-(4-哌嗪-1-苯基)-苯并噁唑 在 甲酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以22%的产率得到2-(4-(4-((5-methylfuran-2-yl)methyl)piperazin-1-yl)phenyl)benzo[d]oxazole
  参考文献：
  名称：

  Discovery and Preliminary Structure–Activity Relationship of Arylpiperazines as Novel, Brain-Penetrant Antiprion Compounds

  摘要：

  Creutzfeldt-Jakob disease and kuru in humans, BSE in cattle, and scrapie in sheep are fatal neurodegenerative disorders. Such illnesses are caused by the conversion and accumulation of a misfolded pathogenic isoform (termed PrPSc) of a normally benign, host cellular protein, denoted PrPC. We employed high-throughput screening enzyme-linked immunosorbent assays to evaluate compounds for their ability to reduce the level of PrPSc in Rocky Mountain Laboratory prion-infected mouse neuroblastoma cells (ScN2a-cl3). Arylpiperazines were among the active compounds identified, but the initial hits suffered from low potency and poor drug-likeness. The best of those hits, such as 1, 7, 13, and 19, displayed moderate antiprion activity with EC50 values in the micromolar range. Key analogues were designed and synthesized on the basis of the structure-activity relationship, with analogues 41, 44, 46, and 47 found to have submicromolar potency. Analogues 41 and 44 were able to penetrate the blood-brain barrier and achieved excellent drug concentrations in the brains of mice after oral dosing. These compounds represent good starting points for further lead optimization in our pursuit of potential drug candidates for the treatment of prion diseases.

  DOI：

  10.1021/ml300472n
• 作为产物：
  描述：

  1-BOC-4-(4-甲酰苯基)哌嗪 在 2,2,6,6-四甲基哌啶氧化物 、 氧气 、 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 15.0h， 生成 2-(4-哌嗪-1-苯基)-苯并噁唑
  参考文献：
  名称：

  Discovery and Preliminary Structure–Activity Relationship of Arylpiperazines as Novel, Brain-Penetrant Antiprion Compounds

  摘要：

  Creutzfeldt-Jakob disease and kuru in humans, BSE in cattle, and scrapie in sheep are fatal neurodegenerative disorders. Such illnesses are caused by the conversion and accumulation of a misfolded pathogenic isoform (termed PrPSc) of a normally benign, host cellular protein, denoted PrPC. We employed high-throughput screening enzyme-linked immunosorbent assays to evaluate compounds for their ability to reduce the level of PrPSc in Rocky Mountain Laboratory prion-infected mouse neuroblastoma cells (ScN2a-cl3). Arylpiperazines were among the active compounds identified, but the initial hits suffered from low potency and poor drug-likeness. The best of those hits, such as 1, 7, 13, and 19, displayed moderate antiprion activity with EC50 values in the micromolar range. Key analogues were designed and synthesized on the basis of the structure-activity relationship, with analogues 41, 44, 46, and 47 found to have submicromolar potency. Analogues 41 and 44 were able to penetrate the blood-brain barrier and achieved excellent drug concentrations in the brains of mice after oral dosing. These compounds represent good starting points for further lead optimization in our pursuit of potential drug candidates for the treatment of prion diseases.

  DOI：

  10.1021/ml300472n