2-[2-(benzyloxy)phenyl]-1H-benzimidazole-4-carboxylic acid | 530112-67-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-[2-(benzyloxy)phenyl]-1H-benzimidazole-4-carboxylic acid
• 英文别名: 2-(2-phenylmethoxyphenyl)-1H-benzimidazole-4-carboxylic acid
• CAS: 530112-67-5
• 化学式: C₂₁H₁₆N₂O₃
• 分子量: 344.37
• InChiKey: UOPGAEMEVKZCPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 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：
  75.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[2-(benzyloxy)phenyl]-1H-benzimidazole-4-carboxylic acid 在 氯化亚砜 作用下， 反应 1.0h， 生成
  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
• 作为产物：
  描述：

  methyl 2-[2-(benzyloxy)phenyl]-1H-benzimidazole-4-carboxylate 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以97%的产率得到2-[2-(benzyloxy)phenyl]-1H-benzimidazole-4-carboxylic acid
  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。
• 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.
• US7294643B2
  申请人：——

  公开号：US7294643B2

  公开（公告）日：2007-11-13
• 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.