2-(2-苯基甲氧基苯基)-1,3-苯并恶唑-4-羧酸 | 186501-25-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-(2-苯基甲氧基苯基)-1,3-苯并恶唑-4-羧酸
• 英文名称: 2-(2'-benzyloxyphenyl)benzoxazole-4-carboxylic acid
• 英文别名: 2-(2-(benzyloxy)phenyl)benzo[d]oxazole-4-carboxylic acid；2-[2-(benzyloxy)phenyl]-1,3-benzoxazole-4-carboxylic acid；2-(2-phenylmethoxyphenyl)-1,3-benzoxazole-4-carboxylic acid
• CAS: 186501-25-7
• 化学式: C₂₁H₁₅NO₄
• mdl: MFCD27939186
• 分子量: 345.354
• InChiKey: PERFTTUODUHMSL-UHFFFAOYSA-N

物化性质

• 熔点：
  103-104 °C
• 沸点：
  551.2±35.0 °C(Predicted)
• 密度：
  1.317±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.047
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(2-苯基甲氧基苯基)-1,3-苯并恶唑-4-羧酸 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 UK-1
  参考文献：
  名称：

  Critical structural motif for the catalytic inhibition of human topoisomerase II by UK-1 and analogs

  摘要：

  Three new analogs of UK-1 have been synthesized and their efficacies as topoisomerase II inhibitors have been determined. Results show that UK-1 and two of these analogs are catalytic inhibitors of topo II and identifies a critical structural motif necessary for enzyme inhibition. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.095
• 作为产物：
  描述：

  2-(2-(benzyloxy)benzoylamino)-3-hydroxybenzoic acid methyl ester 在 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 生成 2-(2-苯基甲氧基苯基)-1,3-苯并恶唑-4-羧酸
  参考文献：
  名称：

  UK-1的全合成

  摘要：

  简明的五步全合成UK-1（一种链霉菌属的新型双（苯并恶唑）代谢产物）。517-02，完成了。UK-1的甲基醚也使用相同的方法分3个步骤合成。两种合成都是通过顺序构建两个衍生自3-羟基邻氨基苯甲酸的苯并恶唑环来完成的。

  DOI：

  10.1016/s0040-4039(96)02288-5

文献信息

• Synthesis, metal ion binding, and biological evaluation of new anticancer 2-(2′-hydroxyphenyl)benzoxazole analogs of UK-1
  作者：Mireya L. McKee、Sean M. Kerwin

  DOI：10.1016/j.bmc.2007.11.019

  日期：2008.2.15

  similar cytotoxicity to this simplified UK-1 analog with improved water solubility. UK-1 and all of these new analogs bind Cu2+ ions better than Mg2+ ions, and the nature of the 4-substituent is important for the Mg2+ ion binding ability of these 2-(2'-hydroxyphenyl)benzoxazoles. Previous studies of a limited number of UK-1 analogs demonstrated a correlation between Mg2+ ion binding ability and cytotoxicity;

  UK-1 是一种双（苯并恶唑）天然产物，对多种人类癌细胞系具有活性。UK-1 的简化类似物 4-carbomethoxy-2-(2'-hydroxyphenyl)benzoxazole 先前被发现对癌细胞系的活性几乎与 UK-1 一样，并且与天然产物相似，与Mg2+、Zn2+等多种金属离子。制备了一系列 4-取代-2-(2'-羟基苯基) 苯并恶唑类似物的这种“最小药效团”的 UK-1。在乳腺癌和肺癌细胞系中检查了这些类似物的抗癌活性。在甲醇中进行分光光度滴定以评估 UK-1 和这些类似物与 Mg2+ 和 Cu2+ 离子配位的能力。尽管没有一种新的类似物比 4-carbomethoxy-2-(2' -羟基苯基）苯并恶唑，一些类似物被鉴定出与这种简化的 UK-1 类似物具有相似的细胞毒性，并具有改善的水溶性。UK-1 和所有这些新类似物比 Mg2+ 离子更好地结合 Cu2+ 离子，并且 4-取代基的性质对于这些
• UK-1 analogues: methods of preparation and use
  申请人：Kerwin M. Sean

  公开号：US20050004188A1

  公开（公告）日：2005-01-06

  The present invention includes a number of structural analogues of UK-1. A comparision of the anticancer activity of the UK-1 analogues with their ability to inhibit the growth of methicillin-sensitive and methicillin-resistant Staphylococcus aureus demonstrates that a structurally simplified analogue of UK-1 retains the natural product's selective activity against cancer cells. Structurally conservative changes to UK-1 that diminish Mg 2+ -binding ability may result in a dramatic decrease in cancer cell cytotoxicity. The results may establish a minimum structural pharmacophore as well as a functional role for Mg 2+ -binding in the selective cytotoxicity of UK-1.

  本发明包括多个UK-1的结构类似物。将UK-1类似物的抗癌活性与其抑制甲氧西林敏感和甲氧西林耐药的金黄色葡萄球菌生长的能力进行比较，结果表明UK-1的一个结构简化类似物保留了该天然产物对癌细胞的选择性活性。对UK-1的结构保守性改变可能会降低其与Mg2+结合的能力，从而导致对癌细胞的细胞毒性显著降低。结果可能确定了最小的结构药效团以及Mg2+结合在UK-1的选择性细胞毒性中的功能角色。
• The total synthesis of UK-1
  作者：Mark R. DeLuca、Sean M. Kerwin

  DOI：10.1016/s0040-4039(96)02288-5

  日期：1997.1

  A concise, five-step total synthesis of UK-1, a novel bis(benzoxazole) metabolite of Streptomyces sp. 517-02, was accomplished. The methyl ether of UK-1 was also synthesized in 3 steps using the same methodology. Both syntheses are accomplished by the sequential construction of two benzoxazole rings derived from 3-hydroxyanthranilic acid.

  简明的五步全合成UK-1（一种链霉菌属的新型双（苯并恶唑）代谢产物）。517-02，完成了。UK-1的甲基醚也使用相同的方法分3个步骤合成。两种合成都是通过顺序构建两个衍生自3-羟基邻氨基苯甲酸的苯并恶唑环来完成的。
• Synthesis and evaluation of anticancer benzoxazoles and benzimidazoles related to UK-1
  作者：Devinder Kumar、Melissa R Jacob、Michael B Reynolds、Sean M Kerwin

  DOI：10.1016/s0968-0896(02)00327-9

  日期：2002.12

  UK-1 is a structurally unique bis(benzoxazole) natural product isolated from a strain of Streptomyces. UK-1 has been reported to possess anticancer activity but no activity against bacteria, yeast, or fungi. Previous work has also demonstrated the ability of UK-1 to bind a variety of di- and tri-valent metal ions, particularly Mg2+ ions, and to form complexes with double-stranded DNA in the presence of Mg2+ ions. Here we report the activity of UK-1 against a wide range of human cancer cell lines. UK- I displays a wide spectrum of potent anticancer activity against leukemia, lymphoma, and certain solid tumor-derived cell lines, with IC50 values as low as 20 nM. but is inactive against Staphylococcus aureus, a methicillin-resistant strain of S. aureus, or Pseudomonas aeruginosa. A series of analogues of the bis(benzoxazole) natural product UK-1 in which the carbomethoxy-substituted benzoxazole ring of the natural product was modified were prepared and evaluated for their anticancer and antibacterial properties. An analogue of UK-1 in which the carbomethoxy-substituted benzoxazole ring was replaced with a carbomethoxy-substituted benzimidazole ring was inactive against human cancer cell lines and the two strains of S. aureus. In contrast, a simplified analogue in which the carbomethoxy-substituted benzoxazole ring was replaced with a carbomethoxy group was almost as active as UK-1 against the four cancer call lines examined but lacked activity against S. aureus. Metal ion binding studies of these analogues demonstrate that they both bind Zn2+ and Ca2+ ions about as well as UK-1. The non-cytotoxic benzimidazole UK-1 analogue binds Mg2+ ions 50-fold weaker than UK-1, whereas the simple benzoxazole analogue binds Mg2+ ions nearly as well as UK-1. These results support a role of Mg2+ ion binding in the selective cytotoxicity of UK-1 and provide a minimal pharmacophore for the selective cytotoxic activity of the natural product. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Synthesis of Caboxamycin and Its Derivatives Using Eco-Friendly Oxidation
  作者：Yoshinobu Tagawa、Hiroki Koba、Kazuhiro Tomoike、Kunihiro Sumoto

  DOI：10.3987/com-11-12138

  日期：——

  The reaction of 3-hydroxyanthranilic acid or methyl 3-hydroxyanthranilate with O-benzylsalicylaldehyde in xylenes gave benzoxazole derivatives, which lead to a novel benzoxazole antibiotic, caboxamycin via debenzylation or demethylation in good yield, in the presence of dry activated carbon and bubbling molecular oxygen. The present reaction involves the simple procedure, easy workup and environmentally benign materials such as reusable activated carbon and molecular oxygen.