(Z)-methyl2-((4-nitrophenyl)(2,4,6-trioxohexahydropyrimidin-5-yl)methylene)hydrazinecarboxylate | 1551641-61-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (Z)-methyl2-((4-nitrophenyl)(2,4,6-trioxohexahydropyrimidin-5-yl)methylene)hydrazinecarboxylate
• 英文别名: methyl N-[(Z)-[(4-nitrophenyl)-(2,4,6-trioxo-1,3-diazinan-5-yl)methylidene]amino]carbamate
• CAS: 1551641-61-2
• 化学式: C₁₃H₁₁N₅O₇
• 分子量: 349.26
• InChiKey: UGRFKXPULXXIFM-CXUHLZMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  172
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  肼基甲酸甲酯 、 5-(4-nitrobenzoyl)pyrimidine-2,4,6-trione 以 甲醇 为溶剂， 反应 3.0h， 以92%的产率得到(Z)-methyl2-((4-nitrophenyl)(2,4,6-trioxohexahydropyrimidin-5-yl)methylene)hydrazinecarboxylate
  参考文献：
  名称：

  Synthesis and antifungal activity of substituted 2,4,6-pyrimidinetrione carbaldehyde hydrazones

  摘要：

  Opportunistic fungal infections caused by the Candida spp. are the most common human fungal infections, often resulting in severe systemic infections-a significant cause of morbidity and mortality in at-risk populations. Azole antifungals remain the mainstay of antifungal treatment for candidiasis, however development of clinical resistance to azoles by Candida spp. limits the drugs' efficacy and highlights the need for discovery of novel therapeutics. Recently, it has been reported that simple hydrazone derivatives have the capability to potentiate antifungal activities in vitro. Similarly, pyrimidinetrione analogs have long been explored by medicinal chemists as potential therapeutics, with more recent focus being on the potential for pyrimidinetrione antimicrobial activity. In this work, we present the synthesis of a class of novel hydrazone-pyrimidinetrione analogs using novel synthetic procedures. In addition, structure-activity relationship studies focusing on fungal growth inhibition were also performed against two clinically significant fungal pathogens. A number of derivatives, including phenylhydrazones of 5-acylpyrimidinetrione exhibited potent growth inhibition at or below 10 mu M with minimal mammalian cell toxicity. In addition, in vitro studies aimed at defining the mechanism of action of the most active analogs provide preliminary evidence that these compound decrease energy production and fungal cell respiration, making this class of analogs promising novel therapies, as they target pathways not targeted by currently available antifungals. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.010

文献信息

• Synthesis and antifungal activity of substituted 2,4,6-pyrimidinetrione carbaldehyde hydrazones
  作者：Donna M. Neumann、Amy Cammarata、Gregory Backes、Glen E. Palmer、Branko S. Jursic

  DOI：10.1016/j.bmc.2013.12.010

  日期：2014.1

  Opportunistic fungal infections caused by the Candida spp. are the most common human fungal infections, often resulting in severe systemic infections-a significant cause of morbidity and mortality in at-risk populations. Azole antifungals remain the mainstay of antifungal treatment for candidiasis, however development of clinical resistance to azoles by Candida spp. limits the drugs' efficacy and highlights the need for discovery of novel therapeutics. Recently, it has been reported that simple hydrazone derivatives have the capability to potentiate antifungal activities in vitro. Similarly, pyrimidinetrione analogs have long been explored by medicinal chemists as potential therapeutics, with more recent focus being on the potential for pyrimidinetrione antimicrobial activity. In this work, we present the synthesis of a class of novel hydrazone-pyrimidinetrione analogs using novel synthetic procedures. In addition, structure-activity relationship studies focusing on fungal growth inhibition were also performed against two clinically significant fungal pathogens. A number of derivatives, including phenylhydrazones of 5-acylpyrimidinetrione exhibited potent growth inhibition at or below 10 mu M with minimal mammalian cell toxicity. In addition, in vitro studies aimed at defining the mechanism of action of the most active analogs provide preliminary evidence that these compound decrease energy production and fungal cell respiration, making this class of analogs promising novel therapies, as they target pathways not targeted by currently available antifungals. (C) 2013 Elsevier Ltd. All rights reserved.