(3-((4-chlorobenzyl)oxy)phenyl)methanol | 79185-42-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (3-((4-chlorobenzyl)oxy)phenyl)methanol
• 英文别名: [3-[(4-Chlorophenyl)methoxy]phenyl]methanol
• CAS: 79185-42-5
• 化学式: C₁₄H₁₃ClO₂
• mdl: MFCD05039670
• 分子量: 248.709
• InChiKey: ZGUUKWQWXCPIIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3-((4-chlorobenzyl)oxy)phenyl)methanol 在 三溴化磷 作用下， 以 二氯甲烷 为溶剂， 生成 1-(bromomethyl)-3-((4-chlorobenzyl)oxy)benzene
  参考文献：
  名称：

  发现和优化新型N-苄基-3,6-二甲基苯并[d]异恶唑-5-胺衍生物作为具有潜在抗癌活性的有效和选择性TRIM24溴结构域抑制剂。

  摘要：

  包含三方基序的蛋白质24（TRIM24），通过其溴结构域被认为是乙酰化H3K23（H3K23ac）的表观遗传阅读器，与几种癌症的发生或发展密切相关。开发TRIM24抑制剂对于功能研究和药物发现具有重要意义。在这里，我们报告从内部库筛选开始，鉴定，优化和评估N-苄基-3,6-二甲基苯并[d]异恶唑-5-胺作为TRIM24溴结构域抑制剂。基于结构的优化在Alphascreen分析中产生了两种有效的选择性化合物11d和11h，IC50值分别为1.88μM和2.53μM。生存力测定证明该系列化合物作为前列腺癌（PC）细胞LNCaP，C4-2B增殖抑制剂的巨大潜力。菌落形成试验进一步支持了这种抑制活性。化合物11d和11h抑制其他癌症类型的细胞增殖，例如非小细胞肺癌（NSCLC）细胞A549，其IC50值分别为1.08μM和0.75μM。这些数据表明化合物11d和11h是有前途的有前途的化合物，有待进一步研究。

  DOI：

  10.1016/j.bioorg.2019.103424
• 作为产物：
  描述：

  methyl 3-((4-chlorobenzyl)oxy)benzoate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.75h， 以71%的产率得到(3-((4-chlorobenzyl)oxy)phenyl)methanol
  参考文献：
  名称：

  Antitrypanosomal Lead Discovery: Identification of a Ligand-Efficient Inhibitor of Trypanosoma cruzi CYP51 and Parasite Growth

  摘要：

  Chagas disease is caused by the intracellular protozoan parasite Trypanosomal cruzi, and current drugs are lacking in terms of desired safety and efficacy profiles. Following on a recently reported high-throughput screening campaign, we have explored initial structure-activity relationships around a class of imidazole-based compounds. This profiling has uncovered compounds 4c (NEU321) and 4j (NEU704), which are potent against in vitro cultures of T. cruzi and are greater than 160-fold selective over host cells. We report in vitro drug metabolism and properties profiling of 4c and show that this chemotype inhibits the T. cruzi CYP51 enzyme, an observation confirmed by X-ray crystallographic analysis. We compare the binding orientation of 4c to that of other, previously reported inhibitors. We show that 4c displays a significantly better ligand efficiency and a shorter synthetic route over previously disclosed CYP51 inhibitors, and should therefore be considered a promising lead compound for further optimization.

  DOI：

  10.1021/jm400012e

文献信息

• Diaryl compounds and pharmaceutical formulations containing them
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0028305A1

  公开（公告）日：1981-05-13

  Known and novel compounds of formula (I) wherein Ar are the same or different and each is a substituted or unsubstituted phenyl group and Z is a bond, sulphur, -CHOH, or -C=O; and X is oxygen, sulphur, -CH2 or -NH- when Y is -CH2; or X is -CH2 when Y is oxygen; or X - Y together is -CH=CH, are active against viruses, especially rhinoviruses. Methods for producing the compounds are described, as are pharmaceutical formulations and methods for administering the compounds to cure or prevent rhinoviral infections.

  已知和新型的式(I)化合物 其中 Ar 相同或不同，且各为取代或未取代的苯基，以及 Z 是键、硫、-CHOH 或 -C=O；以及 当 Y 为-CH2 时，X 为氧、硫、-CH2 或-NH-；或 当 Y 是氧时，X 是-CH2；或 X-Y合起来是-CH=CH，对病毒，特别是鼻病毒有活性。本文介绍了生产这些化合物的方法，以及使用这些化合物治疗或预防鼻病毒感染的药物制剂和方法。
• Discovery and optimization of novel N-benzyl-3,6-dimethylbenzo[d]isoxazol-5-amine derivatives as potent and selective TRIM24 bromodomain inhibitors with potential anti-cancer activities
  作者：Qingqing Hu、Chao Wang、Qiuping Xiang、Rui Wang、Cheng Zhang、Maofeng Zhang、Xiaoqian Xue、Guolong Luo、Xiaomin Liu、Xishan Wu、Yan Zhang、Donghai Wu、Yong Xu

  DOI：10.1016/j.bioorg.2019.103424

  日期：2020.1

  acetylated H3K23 (H3K23ac) via its bromodomain, has been closely involved in tumorigenesis or tumor progression of several cancers. Developing inhibitors of TRIM24 is significant for functional studies and drug discovery. Herein, we report the identification, optimization and evaluation of N-benzyl-3,6-dimethylbenzo[d]isoxazol-5-amines as TRIM24 bromodomain inhibitors starting from an in house library

  包含三方基序的蛋白质24（TRIM24），通过其溴结构域被认为是乙酰化H3K23（H3K23ac）的表观遗传阅读器，与几种癌症的发生或发展密切相关。开发TRIM24抑制剂对于功能研究和药物发现具有重要意义。在这里，我们报告从内部库筛选开始，鉴定，优化和评估N-苄基-3,6-二甲基苯并[d]异恶唑-5-胺作为TRIM24溴结构域抑制剂。基于结构的优化在Alphascreen分析中产生了两种有效的选择性化合物11d和11h，IC50值分别为1.88μM和2.53μM。生存力测定证明该系列化合物作为前列腺癌（PC）细胞LNCaP，C4-2B增殖抑制剂的巨大潜力。菌落形成试验进一步支持了这种抑制活性。化合物11d和11h抑制其他癌症类型的细胞增殖，例如非小细胞肺癌（NSCLC）细胞A549，其IC50值分别为1.08μM和0.75μM。这些数据表明化合物11d和11h是有前途的有前途的化合物，有待进一步研究。
• Antitrypanosomal Lead Discovery: Identification of a Ligand-Efficient Inhibitor of Trypanosoma cruzi CYP51 and Parasite Growth
  作者：Grasiella Andriani、Emanuele Amata、Joel Beatty、Zeke Clements、Brian J. Coffey、Gilles Courtemanche、William Devine、Jessey Erath、Cristin E. Juda、Zdzislaw Wawrzak、JodiAnne T. Wood、Galina I. Lepesheva、Ana Rodriguez、Michael P. Pollastri

  DOI：10.1021/jm400012e

  日期：2013.3.28

  Chagas disease is caused by the intracellular protozoan parasite Trypanosomal cruzi, and current drugs are lacking in terms of desired safety and efficacy profiles. Following on a recently reported high-throughput screening campaign, we have explored initial structure-activity relationships around a class of imidazole-based compounds. This profiling has uncovered compounds 4c (NEU321) and 4j (NEU704), which are potent against in vitro cultures of T. cruzi and are greater than 160-fold selective over host cells. We report in vitro drug metabolism and properties profiling of 4c and show that this chemotype inhibits the T. cruzi CYP51 enzyme, an observation confirmed by X-ray crystallographic analysis. We compare the binding orientation of 4c to that of other, previously reported inhibitors. We show that 4c displays a significantly better ligand efficiency and a shorter synthetic route over previously disclosed CYP51 inhibitors, and should therefore be considered a promising lead compound for further optimization.