4-(3,4-Dichlorbenzyloxy)-benzonitril | 56442-15-0

• 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-(3,4-Dichlorbenzyloxy)-benzonitril
• 英文别名: 4-[(3,4-Dichlorophenyl)methoxy]benzonitrile
• CAS: 56442-15-0
• 化学式: C₁₄H₉Cl₂NO
• mdl: MFCD06626169
• 分子量: 278.138
• InChiKey: VZSIKYBBDORAST-UHFFFAOYSA-N

物化性质

• 熔点：
  114 °C(Solv: ethanol (64-17-5))
• 沸点：
  429.8±35.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  33
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(3,4-Dichlorbenzyloxy)-benzonitril 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 (4-((3,4-dichlorobenzyl)oxy)phenyl)methanamine
  参考文献：
  名称：

  1,4,5-Trisubstituted Imidazole-Based p53–MDM2/MDMX Antagonists with Aliphatic Linkers for Conjugation with Biological Carriers

  摘要：

  The tumor suppressor protein p53, the "guardian of the genome", is inactivated in nearly all cancer types by mutations in the TPS3 gene or by overexpression of its negative regulators, oncoproteins MDM2/MDMX. Recovery of p53 function by disrupting the p53-MDM2/MDMX interaction using small-molecule antagonists could provide an efficient nongenotoxic anticancer therapy. Here we present the syntheses, activities, and crystal structures of the p53-MDM2/MDMX inhibitors based on the 1,4,5-trisubstituted imidazole scaffold which are appended with aliphatic linkers that enable coupling to bioactive carriers. The compounds have favorable properties at both biochemical and cellular levels. The most effective compound 19 is a tight binder of MDM2 and activates p53 in cancer cells that express the wild-type p53, leading to cell cycle arrest and growth inhibition. Crystal structures reveal that compound 19 induces MDM2 dimerization via the aliphatic linker. This unique dimerization-binding mode opens new prospects for the optimization of the p53-MDM2/MDMX inhibitors and conjugation with bioactive carriers.

  DOI：

  10.1021/acs.jmedchem.7b00104
• 作为产物：
  描述：

  4-羟基苯甲腈 、 3,4-二氯氯苄 在 sodium ethanolate 作用下， 生成 4-(3,4-Dichlorbenzyloxy)-benzonitril
  参考文献：
  名称：

  Hypolipidemic analogs of ethyl 4-benzyloxybenzoate

  摘要：

  A series of compounds related to ethyl 4-benzyloxybenzoate was synthesized and evaluated for potential hypolipidemic activity in rats. Structure--activity relationships are discussed in terms of cholesterol-lowering activity together with effects on weight gain and liver lipids. A number of the compounds inhibited cholesterol and free fatty acid biosynthesis from [1-14C]acetate in rat liver slices in vitro. Ethyl 4-benzyloxybenzoate, ethyl-4-benzyloxybenzoic acid, ethyl 4-p-bromobenzyloxybenzoates, and 4-o-methoxybenzyloxyphenyl acetate exhibited the most favorable spectrum of activity.

  DOI：

  10.1021/jm00221a007

文献信息

• US4098816A
  申请人：——

  公开号：US4098816A

  公开（公告）日：1978-07-04
• 1,4,5-Trisubstituted Imidazole-Based p53–MDM2/MDMX Antagonists with Aliphatic Linkers for Conjugation with Biological Carriers
  作者：Aleksandra Twarda-Clapa、Sylwia Krzanik、Katarzyna Kubica、Katarzyna Guzik、Beata Labuzek、Constantinos G. Neochoritis、Kareem Khoury、Kaja Kowalska、Miroslawa Czub、Grzegorz Dubin、Alexander Dömling、Lukasz Skalniak、Tad A. Holak

  DOI：10.1021/acs.jmedchem.7b00104

  日期：2017.5.25

  The tumor suppressor protein p53, the "guardian of the genome", is inactivated in nearly all cancer types by mutations in the TPS3 gene or by overexpression of its negative regulators, oncoproteins MDM2/MDMX. Recovery of p53 function by disrupting the p53-MDM2/MDMX interaction using small-molecule antagonists could provide an efficient nongenotoxic anticancer therapy. Here we present the syntheses, activities, and crystal structures of the p53-MDM2/MDMX inhibitors based on the 1,4,5-trisubstituted imidazole scaffold which are appended with aliphatic linkers that enable coupling to bioactive carriers. The compounds have favorable properties at both biochemical and cellular levels. The most effective compound 19 is a tight binder of MDM2 and activates p53 in cancer cells that express the wild-type p53, leading to cell cycle arrest and growth inhibition. Crystal structures reveal that compound 19 induces MDM2 dimerization via the aliphatic linker. This unique dimerization-binding mode opens new prospects for the optimization of the p53-MDM2/MDMX inhibitors and conjugation with bioactive carriers.
• Hypolipidemic analogs of ethyl 4-benzyloxybenzoate
  作者：Keith H. Baggaley、Robin Fears、Richard M. Hindley、Brian Morgan、Elspeth Murrell、David E. Thorne

  DOI：10.1021/jm00221a007

  日期：1977.11

  A series of compounds related to ethyl 4-benzyloxybenzoate was synthesized and evaluated for potential hypolipidemic activity in rats. Structure--activity relationships are discussed in terms of cholesterol-lowering activity together with effects on weight gain and liver lipids. A number of the compounds inhibited cholesterol and free fatty acid biosynthesis from [1-14C]acetate in rat liver slices in vitro. Ethyl 4-benzyloxybenzoate, ethyl-4-benzyloxybenzoic acid, ethyl 4-p-bromobenzyloxybenzoates, and 4-o-methoxybenzyloxyphenyl acetate exhibited the most favorable spectrum of activity.