2-(4-(piperazin-1-yl)phenyl)oxazole | 220697-59-6

• 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: 2-(4-(piperazin-1-yl)phenyl)oxazole
• 英文别名: 4-(4-Oxazol-2-ylphenyl)piperazine；2-(4-piperazin-1-ylphenyl)-1,3-oxazole
• CAS: 220697-59-6
• 化学式: C₁₃H₁₅N₃O
• 分子量: 229.282
• InChiKey: SRVNVWFWJAOCKP-UHFFFAOYSA-N

物化性质

• 沸点：
  419.2±55.0 °C(Predicted)
• 密度：
  1.151±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  41.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-甲基呋喃醛 、 2-(4-(piperazin-1-yl)phenyl)oxazole 在 甲酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以36%的产率得到2-(4-(4-((5-methylfuran-2-yl)methyl)piperazin-1-yl)phenyl)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：

  tert-butyl 4-(4-(oxazol-2-yl)phenyl)piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以93%的产率得到2-(4-(piperazin-1-yl)phenyl)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

文献信息

• Indole derivatives as 5-HT1B and 5-HT1D agonists
  申请人：——

  公开号：US20020061891A1

  公开（公告）日：2002-05-23

  The invention concerns novel indole piperazine derivatives of formula (I). It also concerns a method for preparing said compounds and their use as therapeutically active substances, in particular for treating or preventing diseases related to the disfunction of 5-HT 1-like receptors.

  这项发明涉及式(I)的新型吲哌啶衍生物。它还涉及制备该化合物的方法以及它们作为治疗活性物质的用途，特别是用于治疗或预防与5-HT1类受体功能障碍相关的疾病。
• DERIVES D'INDOLE COMME AGONISTES DE 5-HT1B ET 5-HT1D
  申请人：PIERRE FABRE MEDICAMENT

  公开号：EP1007524A1

  公开（公告）日：2000-06-14
• PIPERAZINE WITH OR-SUBSTITUTED PHENYL GROUP AND THEIR USE AS GLYT1 INHIBITORS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1656361B1

  公开（公告）日：2008-01-02
• US6277853B1
  申请人：——

  公开号：US6277853B1

  公开（公告）日：2001-08-21
• US6589953B2
  申请人：——

  公开号：US6589953B2

  公开（公告）日：2003-07-08