2-(2-(benzyloxy)benzoylamino)-3-hydroxybenzoic acid methyl ester | 186501-21-3

• 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: 2-(2-(benzyloxy)benzoylamino)-3-hydroxybenzoic acid methyl ester
• 英文别名: methyl 2-{[2-(benzyloxy)benzoyl]amino}-3-hydroxybenzoate；N-(2-hydroxy-6-carbmethoxyphenyl)-2-benzyloxybenzamide；methyl 3-hydroxy-2-[(2-phenylmethoxybenzoyl)amino]benzoate
• CAS: 186501-21-3
• 化学式: C₂₂H₁₉NO₅
• 分子量: 377.397
• InChiKey: PQVBHJYVDMWNCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(2-(benzyloxy)benzoylamino)-3-hydroxybenzoic acid methyl ester 在 对甲苯磺酸 作用下， 以 水 、 甲苯 为溶剂， 反应 1.5h， 以58%的产率得到2-(2-hydroxyphenyl)-4-benzoxazolecarboxylic acid methyl ester
  参考文献：
  名称：

  UK-1 analogues: methods of preparation and use

  摘要：

  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。

  公开号：

  US20050004188A1
• 作为产物：
  描述：

  水杨酸甲酯 在 吡啶 、 sodium hydroxide 、 草酰氯 、 potassium carbonate 、 N,N-二甲基甲酰胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 44.0h， 生成 2-(2-(benzyloxy)benzoylamino)-3-hydroxybenzoic acid methyl ester
  参考文献：
  名称：

  Synthesis and anticancer evaluation of bis(benzimidazoles), bis(benzoxazoles), and benzothiazoles

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2006.05.007

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。
• 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.
• Critical structural motif for the catalytic inhibition of human topoisomerase II by UK-1 and analogs
  作者：Ben B. Wang、Nima Maghami、Vanessa L. Goodlin、Paul J. Smith

  DOI：10.1016/j.bmcl.2004.03.095

  日期：2004.6

  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.
• Synthesis Method of Anti-Cancer Drug UK-1 and Derivatives Thereof
  申请人：Huang Yung-Tzung

  公开号：US20160207909A1

  公开（公告）日：2016-07-21

  A synthesis method of anti-cancer drug UK-1 includes: mixing methyl 2-amino-3-hydroxybenzoate, aldehyde and molecular sieves to form a mixture and firstly refluxing the mixture to form a first reactant; hydrolyzing the first reactant in a basic solution to form a hydrolyzed solution and secondly refluxing the hydrolyzed solution to form a second reactant; and dehydrating the second reactant and the methyl 2-amino-3-hydroxybenzoate in an acidic solution to form a dehydrated solution and thirdly refluxing the dehydrated solution to form an anti-cancer drug UK-1 or at least one derivative thereof.