4-((4-(trifluoromethyl)benzyl)oxy)benzonitrile

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((4-(trifluoromethyl)benzyl)oxy)benzonitrile
• 英文别名: 4-[[4-(Trifluoromethyl)phenyl]methoxy]benzonitrile
• 化学式: C₁₅H₁₀F₃NO
• 分子量: 277.246
• InChiKey: UYNNYSBVWJSVPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  33
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-((4-(trifluoromethyl)benzyl)oxy)benzonitrile 在 O‑(6‑chlorobezotriazol‑1‑yl)‑N,N,N,N‑tetramethyluronium hexafluorophosphate 、 盐酸羟胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 tert-butyl (S)-2-(3-(4-((4-(trifluoromethyl)benzyl)oxy)phenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Discovery of a Small Side Cavity in Sphingosine Kinase 2 that Enhances Inhibitor Potency and Selectivity

  摘要：

  The sphingosine-l-phosphate (SIP) signaling pathway is an attractive drug target due to its involvement in immune cell chemotaxis and vascular integrity. The formation of S1P is catalyzed by sphingosine kinase 1 or 2 (SphK1 or SphK2) from sphingosine (Sph) and ATP. Inhibition of SphK1 and SphK2 to attenuate levels of SIP has been reported to be efficacious in animal models of diseases such as cancer, sickle cell disease, and renal fibrosis. While inhibitors of both SphKs have been reported, improvements in potency and selectivity are still needed. Toward that end, we performed structure-activity relationship profiling of 8 (SLM6031434) and discovered a heretofore unrecognized side cavity that increased inhibitor potency toward SphK2. Interrogating this region revealed that relatively small hydrophobic moieties are preferred, with 10 being the most potent SphK2-selective inhibitor (K-i = 89 nM, 73-fold SphK2-selective) with validated in vivo activity.

  DOI：

  10.1021/acs.jmedchem.9b01508
• 作为产物：
  描述：

  4-羟基苯甲腈 、 1-溴-三氟对二甲苯 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 4.0h， 以57%的产率得到4-((4-(trifluoromethyl)benzyl)oxy)benzonitrile
  参考文献：
  名称：

  联芳基衍生物的合成和评估，用于针对帕金森氏病的选择性单胺氧化酶B抑制剂的结构表征

  摘要：

  苄氧基苯基部分是单胺氧化酶B（MAO-B），沙芬酰胺和司加吉林的高效，选择性和可逆抑制剂的常见结构。我们合成了在末端芳基单元上包含卤素取代基的4-（苄氧基）苯基和联苯-4-基衍生物。另外，我们修饰了胺基和联芳基连接单元之间的碳连接基。在合成的化合物中，12c作为竞争性抑制剂表现出最有效和选择性的MAO-B抑制作用（hMAO-B IC 50：8.9 nM；选择性比MAO-A高10,000倍）。另外，12c与著名的MAO-B抑制剂（例如司来吉兰，沙芬酰胺和sembragiline）相比，具有更高的MAO-B抑制活性和选择性。在MPTP诱发的帕金森氏病（PD）小鼠模型中，12c可显着保护酪氨酸羟化酶（TH）免疫阳性DAergic神经元，并减轻与PD相关的行为缺陷。这项研究表明，作为MAO-B抑制剂的特征结构可能为PD治疗药物的开发提供很好的见识。

  DOI：

  10.1016/j.bmc.2017.11.036

文献信息

• Synthesis and evaluation of biaryl derivatives for structural characterization of selective monoamine oxidase B inhibitors toward Parkinson’s disease therapy
  作者：Seul Ki Yeon、Ji Won Choi、Jong-Hyun Park、Ye Rim Lee、Hyeon Jeong Kim、Su Jeong Shin、Bo Ko Jang、Siwon Kim、Yong-Sun Bahn、Gyoonhee Han、Yong Sup Lee、Ae Nim Pae、Ki Duk Park

  DOI：10.1016/j.bmc.2017.11.036

  日期：2018.1

  inhibitory effect (hMAO-B IC50: 8.9 nM; >10,000-fold selectivity over MAO-A) as a competitive inhibitor. In addition, 12c showed greater MAO-B inhibitory activity and selectivity compared to well-known MAO-B inhibitors such as selegiline, safinamide and sembragiline. In the MPTP-induced mouse model of Parkinson’s disease (PD), 12c significantly protected the tyrosine hydroxylase (TH)-immunopositive DAergic

  苄氧基苯基部分是单胺氧化酶B（MAO-B），沙芬酰胺和司加吉林的高效，选择性和可逆抑制剂的常见结构。我们合成了在末端芳基单元上包含卤素取代基的4-（苄氧基）苯基和联苯-4-基衍生物。另外，我们修饰了胺基和联芳基连接单元之间的碳连接基。在合成的化合物中，12c作为竞争性抑制剂表现出最有效和选择性的MAO-B抑制作用（hMAO-B IC 50：8.9 nM；选择性比MAO-A高10,000倍）。另外，12c与著名的MAO-B抑制剂（例如司来吉兰，沙芬酰胺和sembragiline）相比，具有更高的MAO-B抑制活性和选择性。在MPTP诱发的帕金森氏病（PD）小鼠模型中，12c可显着保护酪氨酸羟化酶（TH）免疫阳性DAergic神经元，并减轻与PD相关的行为缺陷。这项研究表明，作为MAO-B抑制剂的特征结构可能为PD治疗药物的开发提供很好的见识。
• Room-Temperature, Transition-Metal-Free Arylation of Alcohols with Aryl Bromides
  作者：Yanqing Wang、David J. Young、Hong-Xi Li、Da-Liang Zhu、Jie Li、Qi Wu

  DOI：10.1055/a-1932-6146

  日期：2023.2

  Sodium tert-butoxide promotes the efficient etherification of alcohols with aryl bromides at room temperature. This simple procedure has a broad substrate scope, providing a practical pathway to aryl alkyl ethers in good yields without the addition of any transition metal species.

  叔丁醇钠促进醇与芳基溴在室温下的有效醚化。这种简单的过程具有广泛的底物范围，为在不添加任何过渡金属物质的情况下以高收率制备芳基烷基醚提供了一条实用途径。
• 一种溴代芳烃与醇反应合成烷基芳基醚的方法
  申请人：盐城师范学院

  公开号：CN115368271A

  公开（公告）日：2022-11-22

  本发明公开了一种全新的通过无过渡金属催化实现溴代芳烃与醇反应合成烷基芳基醚的应用，其包括如下步骤：在惰性气体保护下，仅以溴代芳烃、醇、叔丁醇钠与溶剂为反应物料，将上述反应物加入到配备搅拌装置的反应容器中，室温搅拌反应4小时，得到烷基芳基醚类化合物。另外，本发明整个过程绿色、高效且易于操作，是一种合成烷基芳基醚类化合物的好方法。
• Discovery of a Small Side Cavity in Sphingosine Kinase 2 that Enhances Inhibitor Potency and Selectivity
  作者：Christopher D. Sibley、Emily A. Morris、Yugesh Kharel、Anne M. Brown、Tao Huang、David R. Bevan、Kevin R. Lynch、Webster L. Santos

  DOI：10.1021/acs.jmedchem.9b01508

  日期：2020.2.13

  The sphingosine-l-phosphate (SIP) signaling pathway is an attractive drug target due to its involvement in immune cell chemotaxis and vascular integrity. The formation of S1P is catalyzed by sphingosine kinase 1 or 2 (SphK1 or SphK2) from sphingosine (Sph) and ATP. Inhibition of SphK1 and SphK2 to attenuate levels of SIP has been reported to be efficacious in animal models of diseases such as cancer, sickle cell disease, and renal fibrosis. While inhibitors of both SphKs have been reported, improvements in potency and selectivity are still needed. Toward that end, we performed structure-activity relationship profiling of 8 (SLM6031434) and discovered a heretofore unrecognized side cavity that increased inhibitor potency toward SphK2. Interrogating this region revealed that relatively small hydrophobic moieties are preferred, with 10 being the most potent SphK2-selective inhibitor (K-i = 89 nM, 73-fold SphK2-selective) with validated in vivo activity.