2'-(2-羟基苯基)-[2,4'-联苯并恶唑]-4-羧酸甲酯 | 151271-53-3

• 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-羟基苯基)-[2,4'-联苯并恶唑]-4-羧酸甲酯
• 英文名称: 2'-(2-hydroxyphenyl)-2,4'-bibenzoxazole-4-carboxylic acid methyl ester
• 英文别名: UK-1；Methyl 2-[2-(2-hydroxyphenyl)-1,3-benzoxazol-4-yl]-1,3-benzoxazole-4-carboxylate
• CAS: 151271-53-3
• 化学式: C₂₂H₁₄N₂O₅
• 分子量: 386.364
• InChiKey: NGKIDJMAXLRJRL-UHFFFAOYSA-N

物化性质

• 熔点：
  209-210℃
• 沸点：
  541.4±30.0 °C(Predicted)
• 密度：
  1.396±0.06 g/cm3(Predicted)
• 溶解度：
  溶于DMSO；溶于二甲基甲酰胺

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  98.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2'-(2-羟基苯基)-[2,4'-联苯并恶唑]-4-羧酸甲酯 在 sodium hydroxide 作用下， 以 吡啶 为溶剂， 反应 6.0h， 生成 demethyl UK-1
  参考文献：
  名称：

  UK-1, a Novel Cytotoxic Metabolite from Strcptomyces sp. 517-02. III. Antibacterial Action of Demethyl UK-1.

  摘要：

  DOI：

  10.7164/antibiotics.50.788
• 作为产物：
  描述：

  2-(2-(benzyloxy)benzoylamino)-3-hydroxybenzoic acid methyl ester 在 吡啶 、 sodium hydroxide 、 草酰氯 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 xylene 为溶剂， 反应 6.0h， 生成 2'-(2-羟基苯基)-[2,4'-联苯并恶唑]-4-羧酸甲酯
  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

• 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。
• 抗癌药物UK-1的合成方法
  申请人：黄荣宗

  公开号：CN107652248A

  公开（公告）日：2018-02-02

  一种抗癌药物UK‑1的合成方法包含：将methyl 2‑amino‑3‑hydroxybenzoate化合物、醛及分子筛进行混合，以产生一混合物，将该混合物进行第一次加热回流，以获得一第一产物；将该第一产物的酯官能基在一碱性溶液中进行水解，并进行第二次加热回流，以形成一第二产物的羧酸官能基；将该第二产物及另一当量的methyl 2‑amino‑3‑hydroxybenzoate化合物在一酸性溶液中进行脱水，并进行第三次加热回流，以合成一抗癌药物UK‑1或一抗癌药物UK‑1衍生物。
• Heterocyclic Benzoxazole Compositions as Inhibitors of Hepatitis C Virus
  申请人：Smith Paul

  公开号：US20120208856A1

  公开（公告）日：2012-08-16

  This invention relates to benzoxazole compounds, compositions and devices for delivering them, processes for manufacturing them, and methods of using them in the treatment of Hepatitis C Virus.

  本发明涉及苯并噁唑化合物、递送它们的组合物和装置、制造它们的过程，以及在治疗丙型肝炎病毒中使用它们的方法。
• Synthesis and anticancer evaluation of bis(benzimidazoles), bis(benzoxazoles), and benzothiazoles
  作者：Shu-Ting Huang、I-Jen Hsei、Chinpiao Chen

  DOI：10.1016/j.bmc.2006.05.007

  日期：2006.9

  Four classes of UK-1 analogues were synthesized and their cytotoxicity testing against human A-549, BFTC-905, RD, MES-SA, and HeLa carcinoma cell lines was determined. The results revealed that UK-1 and four of these analogues (15-18) are potent against the cancer cell lines. In particular, compound 16 is more potent than UK-1 against A-549 and HeLa cell lines, and compounds 15, 17, and 18 selectively exhibit potent cytotoxic activity against the BFTV-905 cells (IC50 9.6 PM), A-549 cells (IC50 6.6 mu M), and MES-SA cells (IC50 9.2 mu M),respectively. (c) 2006 Elsevier Ltd. All rights reserved.
• 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.