2-(4-(4-methoxyphenyl)piperazin-1-yl)-1-phenylethan-1-ol | 95553-55-2

• 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-(4-methoxyphenyl)piperazin-1-yl)-1-phenylethan-1-ol
• 英文别名: 2-[4-(4-methoxy-phenyl)-piperazin-1-yl]-1-phenyl-ethanol；2-[4-(4-methoxyphenyl)piperazin-1-yl]-1-phenylethanol
• CAS: 95553-55-2
• 化学式: C₁₉H₂₄N₂O₂
• 分子量: 312.412
• InChiKey: OIVHENPWWMZLAL-UHFFFAOYSA-N

物化性质

• 沸点：
  489.8±45.0 °C(Predicted)
• 密度：
  1.143±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  35.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(三氟甲基)苯甲酰氯 、 2-(4-(4-methoxyphenyl)piperazin-1-yl)-1-phenylethan-1-ol 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以66.8%的产率得到2-(4-(4-methoxyphenyl)piperazin-1-yl)-1-phenylethyl 3-(trifluoromethyl)benzoate
  参考文献：
  名称：

  Small-Molecule Activator of UNC-51-Like Kinase 1 (ULK1) That Induces Cytoprotective Autophagy for Parkinson’s Disease Treatment

  摘要：

  UNC-51-like kinase 1 (ULK1), the yeast Atg1 ortholog, is the sole serine-threonine kinase and initiating 1, enzyme in autophagy, which may be regarded as a target in Parkinson's disease (PD). Herein, we discovered a small molecule 33i (BL-918) as a potent activator of ULK1 by structure-based drug design. Subsequently, some key amino acid residues (Arg18, Lys50, Asn86, and Tyr89) were found to be crucial to the binding pocket between ULK1 and 33i by site-directed mutagenesis. Moreover, we found that 33i induced autophagy via the ULK complex in SH-SYSY cells. Intriguingly, this activator displayed a cytoprotective effect on MPP+-treated SH-SYSY cells, as well as protected against MPTP-induced motor dysfunction and loss of dopaminergic neurons by targeting ULK1-modulated autophagy in mouse models of PD. Together, these results demonstrate the therapeutic potential to target ULK1, and 33i, the novel activator of ULK1, may serve as a candidate drug for future PD treatment.

  DOI：

  10.1021/acs.jmedchem.7b01575
• 作为产物：
  描述：

  1-(4-甲氧基苯基)哌嗪 在 sodium tetrahydroborate 、 potassium carbonate 、 potassium iodide 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 2.0h， 生成 2-(4-(4-methoxyphenyl)piperazin-1-yl)-1-phenylethan-1-ol
  参考文献：
  名称：

  Small-Molecule Activator of UNC-51-Like Kinase 1 (ULK1) That Induces Cytoprotective Autophagy for Parkinson’s Disease Treatment

  摘要：

  UNC-51-like kinase 1 (ULK1), the yeast Atg1 ortholog, is the sole serine-threonine kinase and initiating 1, enzyme in autophagy, which may be regarded as a target in Parkinson's disease (PD). Herein, we discovered a small molecule 33i (BL-918) as a potent activator of ULK1 by structure-based drug design. Subsequently, some key amino acid residues (Arg18, Lys50, Asn86, and Tyr89) were found to be crucial to the binding pocket between ULK1 and 33i by site-directed mutagenesis. Moreover, we found that 33i induced autophagy via the ULK complex in SH-SYSY cells. Intriguingly, this activator displayed a cytoprotective effect on MPP+-treated SH-SYSY cells, as well as protected against MPTP-induced motor dysfunction and loss of dopaminergic neurons by targeting ULK1-modulated autophagy in mouse models of PD. Together, these results demonstrate the therapeutic potential to target ULK1, and 33i, the novel activator of ULK1, may serve as a candidate drug for future PD treatment.

  DOI：

  10.1021/acs.jmedchem.7b01575

文献信息

• Small-Molecule Activator of UNC-51-Like Kinase 1 (ULK1) That Induces Cytoprotective Autophagy for Parkinson’s Disease Treatment
  作者：Liang Ouyang、Lan Zhang、Shouyue Zhang、Dahong Yao、Yuqian Zhao、Guan Wang、Leilei Fu、Peng Lei、Bo Liu

  DOI：10.1021/acs.jmedchem.7b01575

  日期：2018.4.12

  UNC-51-like kinase 1 (ULK1), the yeast Atg1 ortholog, is the sole serine-threonine kinase and initiating 1, enzyme in autophagy, which may be regarded as a target in Parkinson's disease (PD). Herein, we discovered a small molecule 33i (BL-918) as a potent activator of ULK1 by structure-based drug design. Subsequently, some key amino acid residues (Arg18, Lys50, Asn86, and Tyr89) were found to be crucial to the binding pocket between ULK1 and 33i by site-directed mutagenesis. Moreover, we found that 33i induced autophagy via the ULK complex in SH-SYSY cells. Intriguingly, this activator displayed a cytoprotective effect on MPP+-treated SH-SYSY cells, as well as protected against MPTP-induced motor dysfunction and loss of dopaminergic neurons by targeting ULK1-modulated autophagy in mouse models of PD. Together, these results demonstrate the therapeutic potential to target ULK1, and 33i, the novel activator of ULK1, may serve as a candidate drug for future PD treatment.