1-methyl-4-nitro-N-[2-(1-pyrrolidinyl)ethyl]-1H-pyrrole-2-carboxamide | 1108614-47-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-methyl-4-nitro-N-[2-(1-pyrrolidinyl)ethyl]-1H-pyrrole-2-carboxamide
• 英文别名: 1-methyl-4-nitro-N-(2-(pyrrolidin-1-yl)ethyl)-1H-pyrrole-2-carboxamide；1-methyl-4-nitro-N-(2-pyrrolidin-1-ylethyl)pyrrole-2-carboxamide
• CAS: 1108614-47-6
• 化学式: C₁₂H₁₈N₄O₃
• 分子量: 266.3
• InChiKey: QMSQNRMYFPJFPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-methyl-4-nitro-N-[2-(1-pyrrolidinyl)ethyl]-1H-pyrrole-2-carboxamide 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 1.5h， 生成 4-amino-1-methyl-N-(2-pyrrolidin-1-ylethyl)pyrrole-2-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of Benzophenone-Based Tetraamides as Novel Antibacterial Agents

  摘要：

  The increase in the incidence of both hospital- and community-acquired antibiotic-resistant infections is a major concern to the healthcare community. There have been only two new classes of antibiotics approved by the FDA over the past 40 years, and clearly there is a growing need For additional antimicrobial agents. In this paper, we present Our work on the discovery of a class of benzophenone containing compounds that possess good activity against MRSA, VISA, VRSA, and VRE and moderate activity against E. coli. These compounds display MIC values in the 0.5-2.0 mg/L range and are not cytotoxic against mammalian cells. Extensive structure-activity relationship studies revealed that the benzophenone was absolutely essential for antibacterial activity as was the presence of a cationic group. Although these agents display DNA binding activity, we observed that these compounds do not inhibit any macromolecular synthesis reliant upon DNA nor do they inhibit lipid or cell wall biosynthesis. Instead, we found that these agents cause membrane depolarization, indicating that the bacterial membrane was the primary site of action for these agents. Our studies Suggest that caution should be taken ill assigning the mechanism of action for DNA binding antibiotics.

  DOI：

  10.1021/jm900519b
• 作为产物：
  描述：

  1-(2-氨乙基)吡咯烷 、 1-甲基-4-硝基-2-(三氟乙酰)-1H-吡咯 以 N,N-二甲基甲酰胺 为溶剂， 以95%的产率得到1-methyl-4-nitro-N-[2-(1-pyrrolidinyl)ethyl]-1H-pyrrole-2-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of Benzophenone-Based Tetraamides as Novel Antibacterial Agents

  摘要：

  The increase in the incidence of both hospital- and community-acquired antibiotic-resistant infections is a major concern to the healthcare community. There have been only two new classes of antibiotics approved by the FDA over the past 40 years, and clearly there is a growing need For additional antimicrobial agents. In this paper, we present Our work on the discovery of a class of benzophenone containing compounds that possess good activity against MRSA, VISA, VRSA, and VRE and moderate activity against E. coli. These compounds display MIC values in the 0.5-2.0 mg/L range and are not cytotoxic against mammalian cells. Extensive structure-activity relationship studies revealed that the benzophenone was absolutely essential for antibacterial activity as was the presence of a cationic group. Although these agents display DNA binding activity, we observed that these compounds do not inhibit any macromolecular synthesis reliant upon DNA nor do they inhibit lipid or cell wall biosynthesis. Instead, we found that these agents cause membrane depolarization, indicating that the bacterial membrane was the primary site of action for these agents. Our studies Suggest that caution should be taken ill assigning the mechanism of action for DNA binding antibiotics.

  DOI：

  10.1021/jm900519b

文献信息

• A divergent synthesis of minor groove binders with tail group variation
  作者：David Breen、Alan R. Kennedy、Colin J. Suckling

  DOI：10.1039/b814452d

  日期：——

  A new synthesis of polyamide minor groove binders in which diversity is introduced by the nucleophilic substitution of a 2-sulfido-1,3,2-diazaphospholidinyloxy substituent by volatile secondary amine nucleophiles is described. Such a method has potential value for economically investigating structure–activity relationships in this important class of compounds through library synthesis. As an example using this method are prepared two new minor groove binders with pyrrolidinyl or piperidinyl tail groups that are close relatives of highly active antibacterial minor groove binders with morpholinyl tail groups. The antibacterial activity found against Staphylococcus aureus and Mycobacterium spp. indicates that the pKa of this set of compounds is not the dominant factor in determining the antibacterial activity.

  描述了一种新的聚酰胺小沟结合剂的合成方法，该方法通过挥发性的二级胺亲核试剂对2-硫代-1,3,2-二氮杂膦啉氧取代基进行亲核取代，从而引入了多样性。这种方法在经济上研究这一重要化合物类的结构-活性关系方面具有潜在价值，通过文库合成进行探讨。作为这种方法的一个例子，合成了两种新的小沟结合剂，分别具有吡咯烷基或哌啶基尾部，它们与带有吗啉基尾部的高活性抗菌小沟结合剂密切相关。针对金黄色葡萄球菌和分枝杆菌群体的抗菌活性表明，这类化合物的pKa并不是决定抗菌活性的主导因素。
• Design, Synthesis, and Structure−Activity Relationships of Benzophenone-Based Tetraamides as Novel Antibacterial Agents
  作者：Sunil K. Vooturi、Chrissy M. Cheung、Michael J. Rybak、Steven M. Firestine

  DOI：10.1021/jm900519b

  日期：2009.8.27

  The increase in the incidence of both hospital- and community-acquired antibiotic-resistant infections is a major concern to the healthcare community. There have been only two new classes of antibiotics approved by the FDA over the past 40 years, and clearly there is a growing need For additional antimicrobial agents. In this paper, we present Our work on the discovery of a class of benzophenone containing compounds that possess good activity against MRSA, VISA, VRSA, and VRE and moderate activity against E. coli. These compounds display MIC values in the 0.5-2.0 mg/L range and are not cytotoxic against mammalian cells. Extensive structure-activity relationship studies revealed that the benzophenone was absolutely essential for antibacterial activity as was the presence of a cationic group. Although these agents display DNA binding activity, we observed that these compounds do not inhibit any macromolecular synthesis reliant upon DNA nor do they inhibit lipid or cell wall biosynthesis. Instead, we found that these agents cause membrane depolarization, indicating that the bacterial membrane was the primary site of action for these agents. Our studies Suggest that caution should be taken ill assigning the mechanism of action for DNA binding antibiotics.