1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-4-phenyl-1H-1,2,3-triazole | 1144040-32-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-4-phenyl-1H-1,2,3-triazole
• 英文别名: 1-[2-(2-methyl-5-nitro-imidazol-1-yl)ethyl]-4-phenyl-1H-[1,2,3]triazole；1-[2-(2-Methyl-5-nitroimidazol-1-yl)ethyl]-4-phenyltriazole
• CAS: 1144040-32-3
• 化学式: C₁₄H₁₄N₆O₂
• 分子量: 298.304
• InChiKey: GRRXULDRKJWQLK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  94.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-4-phenyl-1H-1,2,3-triazole 、 4-氯苯甲醛 在 sodium methylate 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 12.0h， 以38%的产率得到(E)-1-(2-(2-(4-chlorostyryl)-5-nitro-1H-imidazol-1-yl)ethyl)-4-phenyl-1H-1,2,3-triazole
  参考文献：
  名称：

  Synthesis, antiamoebic activity and docking studies of metronidazole-triazole-styryl hybrids

  摘要：

  A series of 22 novel metronidazole-triazole-styryl hybrids were synthesized and evaluated for their in vitro antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Some of the hybrids were found to be more active (IC50 = 0.12-035 mu M) than the reference drug metronidazole (IC50=1.79 mu M). The most active compounds were found to be non-toxic (up to 50 mu M) against the Vero cells showing a good safety profile of these hybrids. The docking and ADMET studies were also conducted to investigate the probable mode of action. Docking studies showed significant binding affinity in the active site of E. histolytica thioredoxin reductase (EhTrR) protein. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.03.033
• 作为产物：
  描述：

  甲硝唑 在 4-二甲氨基吡啶 、 copper(l) iodide 、 sodium azide 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 11.0h， 生成 1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-4-phenyl-1H-1,2,3-triazole
  参考文献：
  名称：

  新型甲硝唑连接的 1H-1,2,3-三唑和羧酸盐部分对 α-葡萄糖苷酶的生化和计算抑制：动力学和动态研究

  摘要：

  在当前的研究中，通过体外计算方法评估了含有 1H-1,2,3-三唑和羧酸盐部分的甲硝唑衍生物的抗糖尿病潜力。

  DOI：

  10.1080/07391102.2024.2322622

文献信息

• Expanded therapeutic potential in activity space of next-generation 5-nitroimidazole antimicrobials with broad structural diversity
  作者：Yukiko Miyamoto、Jarosław Kalisiak、Keith Korthals、Tineke Lauwaet、Dae Young Cheung、Ricardo Lozano、Eduardo R. Cobo、Peter Upcroft、Jacqueline A. Upcroft、Douglas E. Berg、Frances D. Gillin、Valery V. Fokin、K. Barry Sharpless、Lars Eckmann

  DOI：10.1073/pnas.1302664110

  日期：2013.10.22

  Drugs against disease-causing microbes are among the major achievements of modern medicine, but many microbes show a tenacious ability to develop resistance, so they are no longer killed by available drugs. We show here for an important class of these drugs, represented by the common drug metronidazole, that broad modifications of the basic drug structure can improve drug activities against several clinically important microbes and unexpectedly overcome different forms of resistance. Several of these new drugs cure infections in animal models and are safe in initial toxicity evaluations. These findings provide reasons to develop this class of drugs as human medicines in the ongoing fight against disease-causing microbes.

  《意义》 药物对抗致病微生物是现代医学的重大成就之一，但许多微生物表现出顽强的耐药能力，因此它们不再被现有药物杀死。我们在这里展示了针对这些药物的一类重要药物（如常见药物甲硝唑）的广泛结构修改可以改善药物对多种临床重要微生物的活性，并意外地克服了不同形式的耐药性。其中几种新药物治愈了动物模型中的感染，并在初步毒性评估中表现安全。这些发现为在持续对抗致病微生物的斗争中将这类药物开发为人类药物提供了理由。
• Anti-methicillin resistant Staphylococcus aureus activity, synergism with oxacillin and molecular docking studies of metronidazole-triazole hybrids
  作者：Beena Negi、Deepak Kumar、Widuranga Kumbukgolla、Sampath Jayaweera、Prija Ponnan、Ramandeep Singh、Sakshi Agarwal、Diwan S. Rawat

  DOI：10.1016/j.ejmech.2016.03.041

  日期：2016.6

  MRSA causes 60-70% of Staphylococcus aureus infection in hospitals and it has developed resistance against the currently available drugs. Interestingly, a series of 35 metronidazole-triazole hybrids on screening against MRSA were found to be active. Compound 22 was found to be effective at 4 mu g/mL concentration against nine strains of MRSA. The inhibitory activity was further enhanced upto 1 mu g/mL when this compound was used in combination with oxacillin in 1:1 ratio. All the compounds were found to be non-toxic in THP-1 cell line upto a concentration of 50 mu M. The time-kill kinetics studies suggested bacteriostatic nature of the compounds. In silico studies show that these compounds interact with Thr600, Ser598, Asn464, His583 and Tyr446 in the active site of PBP2a crystal structure from MRSA. (C) 2016 Elsevier Masson SAS. All rights reserved.
• Synthesis and antibacterial activity evaluation of metronidazole–triazole conjugates
  作者：Beena、Nitin Kumar、Rajesh K. Rohilla、N. Roy、Diwan S. Rawat

  DOI：10.1016/j.bmcl.2009.01.037

  日期：2009.3

  Synthesis and antibacterial activity of metronidazole-triazole conjugates are reported. Total 21 hybrid compounds have been synthesized with different substitution pattern on the triazole ring in order to study their influence on the antibacterial activity. These compounds demonstrated potent to weak antibacterial activity against Gram-positive, and Gram-negative bacteria. Six compounds have shown equal or better antibacterial activity against Gram-negative strains than the reference compound. (C) 2009 Elsevier Ltd. All rights reserved.
• Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites
  作者：Angie M. Jarrad、Tomislav Karoli、Anjan Debnath、Chin Yen Tay、Johnny X. Huang、Geraldine Kaeslin、Alysha G. Elliott、Yukiko Miyamoto、Soumya Ramu、Angela M. Kavanagh、Johannes Zuegg、Lars Eckmann、Mark A.T. Blaskovich、Matthew A. Cooper

  DOI：10.1016/j.ejmech.2015.06.019

  日期：2015.8

  Metronidazole has been used clinically for over 50 years as an antiparasitic and broad-spectrum antibacterial agent effective against anaerobic bacteria. However resistance to metronidazole in parasites and bacteria has been reported, and improved second-generation metronidazole analogues are needed. The copper catalysed Huigsen azide-alkyne 1,3-dipolar cycloaddition offers a way to efficiently assemble new libraries of metronidazole analogues. Several new metronidazole-triazole conjugates (Mtz-triazoles) have been identified with excellent broad spectrum antimicrobial and antiparasitic activity targeting Clostridium difficile, Entamoeba histolytica and Giardia lambda. Cross resistance to metronidazole was observed against stable metronidazole resistant C. difficile and G.. lamblia strains. However for the most potent Mtz-triazoles, the activity remained in a therapeutically relevant window. (C) 2015 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
• Synthesis, antiamoebic activity and docking studies of metronidazole-triazole-styryl hybrids
  作者：Beena Negi、Prija Poonan、Mohammad Fawad Ansari、Deepak Kumar、Sakshi Aggarwal、Ramandeep Singh、Amir Azam、Diwan S. Rawat

  DOI：10.1016/j.ejmech.2018.03.033

  日期：2018.4

  A series of 22 novel metronidazole-triazole-styryl hybrids were synthesized and evaluated for their in vitro antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Some of the hybrids were found to be more active (IC50 = 0.12-035 mu M) than the reference drug metronidazole (IC50=1.79 mu M). The most active compounds were found to be non-toxic (up to 50 mu M) against the Vero cells showing a good safety profile of these hybrids. The docking and ADMET studies were also conducted to investigate the probable mode of action. Docking studies showed significant binding affinity in the active site of E. histolytica thioredoxin reductase (EhTrR) protein. (C) 2018 Elsevier Masson SAS. All rights reserved.