2-[4-(4-methoxylphenyl)piperazin-1-yl]-1-acetophenone | 338396-68-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[4-(4-methoxylphenyl)piperazin-1-yl]-1-acetophenone
• 英文别名: 2-(4-(4-methoxyphenyl)piperazin-1-yl)-1-phenylethan-1-one；2-(4-(4-methoxyphenyl)piperazin-1-yl)-1-phenylethanone；2-[4-(4-Methoxyphenyl)piperazin-1-yl]-1-phenylethanone
• CAS: 338396-68-2
• 化学式: C₁₉H₂₂N₂O₂
• 分子量: 310.396
• InChiKey: USOKYESIBPHMER-UHFFFAOYSA-N

物化性质

• 熔点：
  107-109 °C(Solv: isopropanol (67-63-0))
• 沸点：
  484.6±45.0 °C(Predicted)
• 密度：
  1.133±0.06 g/cm3(Predicted)
• 溶解度：
  >46.6 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[4-(4-methoxylphenyl)piperazin-1-yl]-1-acetophenone 在 sodium tetrahydroborate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 2-(4-(4-methoxyphenyl)piperazin-1-yl)-1-phenylethyl 2-fluorobenzoate
  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 、 alpha-氯乙酰苯 在 sodium carbonate 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以85%的产率得到2-[4-(4-methoxylphenyl)piperazin-1-yl]-1-acetophenone
  参考文献：
  名称：

  Design, Synthesis and Biological Activity Evaluation of Arylpiperazine Derivatives for the Treatment of Neuropathic Pain

  摘要：

  在这项工作中，一系列苯基哌嗪衍生物被合成并通过体内药理学试验进行筛选。在测试的化合物中，2-(4-(3-(三氟甲基)苯基)哌嗪-1-基)-1-苯乙酮（18）和2-(4-(2,3-二甲基苯基)哌嗪-1-基)-1-苯乙酮（19）在小鼠扭体和大鼠热板实验中表现出强大的镇痛活性。在扭体实验中，它们相对于对照组显示出超过70%的抑制率，且在热板测试中分别将延迟时间增加了116.0%和134.4%。此外，化合物18在没有镇静副作用的情况下，在福尔马林痛和神经病理性痛模型中也表现出活性。

  DOI：

  10.3390/molecules16075785

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.
• Design, Synthesis and Biological Activity Evaluation of Arylpiperazine Derivatives for the Treatment of Neuropathic Pain
  作者：Yin Chen、Guan Wang、Xiangqing Xu、Bi-Feng Liu、Jianqi Li、Guisen Zhang

  DOI：10.3390/molecules16075785

  日期：——

  In this work, a series of arylpiperazine derivatives were synthesized and screened by in vivo pharmacological trials. Among the tested compounds, 2-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)-1-phenylethanone (18) and 2-(4-(2,3-dimethylphenyl)piperazin-1-yl)-1-phenylethanone (19) exhibited potent analgesic activities in both the mice writhing and mice hot plate tests. They showed more than 70% inhibition relative to controls in the writhing test, and increased latency by 116.0% and 134.4%, respectively, in the hot plate test. Furthermore, compound 18 was also active in the models of formalin pain and neuropathic pain without sedative side effects.

  在这项工作中，一系列苯基哌嗪衍生物被合成并通过体内药理学试验进行筛选。在测试的化合物中，2-(4-(3-(三氟甲基)苯基)哌嗪-1-基)-1-苯乙酮（18）和2-(4-(2,3-二甲基苯基)哌嗪-1-基)-1-苯乙酮（19）在小鼠扭体和大鼠热板实验中表现出强大的镇痛活性。在扭体实验中，它们相对于对照组显示出超过70%的抑制率，且在热板测试中分别将延迟时间增加了116.0%和134.4%。此外，化合物18在没有镇静副作用的情况下，在福尔马林痛和神经病理性痛模型中也表现出活性。