(E)-1-[2-(3,4-dihydroxy-5-oxo-5H-furan-2-ylidene)ethyl]-1H-1,2,4-triazole-3-carboxylic acid methyl ester | 1380084-27-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢呋喃
• 英文名称: (E)-1-[2-(3,4-dihydroxy-5-oxo-5H-furan-2-ylidene)ethyl]-1H-1,2,4-triazole-3-carboxylic acid methyl ester
• 英文别名: methyl 1-[(2E)-2-(3,4-dihydroxy-5-oxo-2-furylidene)ethyl]-1,2,4-triazole-3-carboxylate；methyl 1-[(2E)-2-(3,4-dihydroxy-5-oxofuran-2-ylidene)ethyl]-1,2,4-triazole-3-carboxylate
• CAS: 1380084-27-4
• 化学式: C₁₀H₉N₃O₆
• 分子量: 267.198
• InChiKey: UVWYRROKKOMQEE-GORDUTHDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-[2-(3,4-bis-benzyloxy-5-oxo-5H-furan-2-ylidene)ethyl]-1H-1,2,4-triazole-3-carboxylic acid methyl ester 在 三氯化硼 、 甲醇 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (E)-1-[2-(3,4-dihydroxy-5-oxo-5H-furan-2-ylidene)ethyl]-1H-1,2,4-triazole-3-carboxylic acid methyl ester 、 (Z)-1-[2-(3,4-dihydroxy-5-oxo-5H-furan-2-ylidene)ethyl]-1H-1,2,4-triazole-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Novel 1,2,4-triazole and imidazole derivatives of l-ascorbic and imino-ascorbic acid: Synthesis, anti-HCV and antitumor activity evaluations

  摘要：

  Several novel 1,2,4-triazole and imidazole L-ascorbic acid (1, 2, 3, 5, 6 and 9) and imino-ascorbic acid (4, 7 and 8) derivatives were prepared and evaluated for their inhibitory activity against hepatitis C virus (HCV) replication and human tumour cell proliferation. Compounds 6 and 9 exerted the most pronounced cytostatic effects in all tumour cell lines tested, and were highly selective for human T-cell acute lymphoblastic leukaemia cells (CEM/0) with IC(50)s of 10 +/- 4 and 7.3 +/- 0.1 mu M, respectively. Unlike compound 9, compound 6 showed no toxicity in human diploid fibroblasts. One of the possible mechanisms of action of compound 6 accounting for observed cytostatic activity towards haematological malignancies might be inhibition of inosine monophosphate dehydrogenase (IMPDH) activity, a key enzyme of de novo purine nucleotide biosynthesis providing the cells with precursors for DNA and RNA synthesis indispensable for cell growth and division, which has emerged as an important target for antileukemic therapy. In addition, this compound proved to be the most potent inhibitor of the hepatitis C virus replication as well. However, observed antiviral effect was most likely associated with the effect that the compound exerted on the host cell rather than with selective effect on the replication of the virus itself. In conclusion, results of this study put forward compound 6 as a potential novel antitumor agent (IMPDH inhibitor) for treating leukaemia. Its significant biological activity and low toxicity in human diploid fibroblasts encourage further development of this compound as a lead. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.01.054

文献信息

• Novel 1,2,4-triazole and imidazole derivatives of l-ascorbic and imino-ascorbic acid: Synthesis, anti-HCV and antitumor activity evaluations
  作者：Karlo Wittine、Maja Stipković Babić、Damjan Makuc、Janez Plavec、Sandra Kraljević Pavelić、Mirela Sedić、Krešimir Pavelić、Pieter Leyssen、Johan Neyts、Jan Balzarini、Mladen Mintas

  DOI：10.1016/j.bmc.2012.01.054

  日期：2012.6

  Several novel 1,2,4-triazole and imidazole L-ascorbic acid (1, 2, 3, 5, 6 and 9) and imino-ascorbic acid (4, 7 and 8) derivatives were prepared and evaluated for their inhibitory activity against hepatitis C virus (HCV) replication and human tumour cell proliferation. Compounds 6 and 9 exerted the most pronounced cytostatic effects in all tumour cell lines tested, and were highly selective for human T-cell acute lymphoblastic leukaemia cells (CEM/0) with IC(50)s of 10 +/- 4 and 7.3 +/- 0.1 mu M, respectively. Unlike compound 9, compound 6 showed no toxicity in human diploid fibroblasts. One of the possible mechanisms of action of compound 6 accounting for observed cytostatic activity towards haematological malignancies might be inhibition of inosine monophosphate dehydrogenase (IMPDH) activity, a key enzyme of de novo purine nucleotide biosynthesis providing the cells with precursors for DNA and RNA synthesis indispensable for cell growth and division, which has emerged as an important target for antileukemic therapy. In addition, this compound proved to be the most potent inhibitor of the hepatitis C virus replication as well. However, observed antiviral effect was most likely associated with the effect that the compound exerted on the host cell rather than with selective effect on the replication of the virus itself. In conclusion, results of this study put forward compound 6 as a potential novel antitumor agent (IMPDH inhibitor) for treating leukaemia. Its significant biological activity and low toxicity in human diploid fibroblasts encourage further development of this compound as a lead. (C) 2012 Elsevier Ltd. All rights reserved.