tert-butyl N-benzyl-N-({[8-({8-[({[(tert-butoxy)carbonyl]amino}({[(tert-butoxy)carbonyl]imino})methyl)amino]octyl}amino)octyl]amino}({[(tert-butoxy)carbonyl]imino})methyl)carbamate | 1176818-05-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl N-benzyl-N-({[8-({8-[({[(tert-butoxy)carbonyl]amino}({[(tert-butoxy)carbonyl]imino})methyl)amino]octyl}amino)octyl]amino}({[(tert-butoxy)carbonyl]imino})methyl)carbamate
• 英文别名: 1-(N1,N2-bis(tert-butoxycarbonyl)guanidine)-17-(N1,N2-bis(tert-butoxycarbonyl)-N1-(benzyl)guanidine)-9-azaheptadecane；tert-butyl N-benzyl-N-[N'-[8-[8-[bis[(2-methylpropan-2-yl)oxycarbonylamino]methylideneamino]octylamino]octyl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate
• CAS: 1176818-05-5
• 化学式: C₄₅H₇₉N₇O₈
• 分子量: 846.164
• InChiKey: OFSMDBOAOMYXIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.3
• 重原子数：
  60
• 可旋转键数：
  32
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  181
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  三光气 、 tert-butyl N-benzyl-N-({[8-({8-[({[(tert-butoxy)carbonyl]amino}({[(tert-butoxy)carbonyl]imino})methyl)amino]octyl}amino)octyl]amino}({[(tert-butoxy)carbonyl]imino})methyl)carbamate 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以57%的产率得到tert‐butyl N‐benzyl‐N‐({[8‐({8‐[({[(tert‐butoxy)carbonyl]amino}({[(tert‐butoxy)carbonyl]imino})methyl)amino]octyl}(chlorocarbonyl)amino)octyl]amino}({[(tert‐butoxy)carbonyl]imino})methyl)carbamate
  参考文献：
  名称：

  Alkyl-guanidine Compounds as Potent Broad-Spectrum Antibacterial Agents: Chemical Library Extension and Biological Characterization

  摘要：

  Nowadays, the increasing of multidrug-resistant pathogenic bacteria represents a serious threat to public health, and the lack of new antibiotics is becoming a global emergency. Therefore, research in antibacterial fields is urgently needed to expand the currently available arsenal of drugs. We have recently reported an alkyl-guanidine derivative (2), characterized by a symmetrical dimeric structure, as a good candidate for further developments, with a high antibacterial activity against both Gram-positive and Gram-negative strains. In this study, starting from its chemical scaffold, we synthesized a small library of analogues. Moreover, biological and in vitro pharmacokinetic characterizations were conducted on some selected derivatives, revealing notable properties: broad-spectrum profile, activity against resistant clinical isolates, and appreciable aqueous solubility. Interestingly, 2 seems neither to select for resistant strains nor to macroscopically alter the membranes, but further studies are required to determine the mode of action.

  DOI：

  10.1021/acs.jmedchem.8b00619
• 作为产物：
  描述：

  1-azido-8-bromooctane 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三苯基膦 、 potassium iodide 作用下， 以 四氢呋喃 、 甲醇 、 溶剂黄146 、 异丙醇 、 正丁醇 为溶剂， 反应 113.0h， 生成 tert-butyl N-benzyl-N-({[8-({8-[({[(tert-butoxy)carbonyl]amino}({[(tert-butoxy)carbonyl]imino})methyl)amino]octyl}amino)octyl]amino}({[(tert-butoxy)carbonyl]imino})methyl)carbamate
  参考文献：
  名称：

  Alkyl-guanidine Compounds as Potent Broad-Spectrum Antibacterial Agents: Chemical Library Extension and Biological Characterization

  摘要：

  Nowadays, the increasing of multidrug-resistant pathogenic bacteria represents a serious threat to public health, and the lack of new antibiotics is becoming a global emergency. Therefore, research in antibacterial fields is urgently needed to expand the currently available arsenal of drugs. We have recently reported an alkyl-guanidine derivative (2), characterized by a symmetrical dimeric structure, as a good candidate for further developments, with a high antibacterial activity against both Gram-positive and Gram-negative strains. In this study, starting from its chemical scaffold, we synthesized a small library of analogues. Moreover, biological and in vitro pharmacokinetic characterizations were conducted on some selected derivatives, revealing notable properties: broad-spectrum profile, activity against resistant clinical isolates, and appreciable aqueous solubility. Interestingly, 2 seems neither to select for resistant strains nor to macroscopically alter the membranes, but further studies are required to determine the mode of action.

  DOI：

  10.1021/acs.jmedchem.8b00619

文献信息

• Synthesis of linear and cyclic guazatine derivatives endowed with antibacterial activity
  作者：Giorgio Maccari、Stefania Sanfilippo、Filomena De Luca、Davide Deodato、Alexandru Casian、Maria Chiara Dasso Lang、Claudio Zamperini、Elena Dreassi、Gian Maria Rossolini、Jean-Denis Docquier、Maurizio Botta

  DOI：10.1016/j.bmcl.2014.09.081

  日期：2014.12

  Antibiotic resistance has reached alarming levels in many clinically-relevant human pathogens, and there is an increasing clinical need for new antibiotics active on drug-resistant Gram-negative pathogens who rapidly evolve towards pandrug resistance phenotypes. Here, we report on two related classes of guanidinic compounds endowed with antibacterial activity. The two best compounds (9a and 13d) exhibited the most potent antibacterial activity with MIC values ranging 0.12-8 mu g/ml with most tested pathogens, including both Gram-positive and Gram-negative bacteria. Interestingly, MIC values were not affected (1-8 mu g/ml) when measured using recent clinical isolates with various antibiotic resistance determinants. The results reported herein identify guazatine derivatives as an interesting starting point for the optimization of a potentially novel class of antibacterial agents. (C) 2014 Elsevier Ltd. All rights reserved.
• Synthesis and Biological Evaluation of Guanidino Compounds Endowed with Subnanomolar Affinity as Competitive Inhibitors of Maize Polyamine Oxidase
  作者：Fabrizio Manetti、Alessandra Cona、Lucilla Angeli、Claudia Mugnaini、Francesco Raffi、Caterina Capone、Elena Dreassi、Alessandra Tania Zizzari、Alessandra Tisi、Rodolfo Federico、Maurizio Botta

  DOI：10.1021/jm900371z

  日期：2009.8.13

  Previous studies on agmatine and its derivatives suggested that the presence of hydrophobic groups on the guanidine moiety was a crucial key for inhibitory activity of maize polyamine oxidase. Accordingly, new lipophilic agmatine and iminoctadine derivatives were synthesized and tested for their ability to inhibit this enzyme. Several compounds showed an affinity in the nanomolar range, while a cyclopropylmethyl derivative of iminoctadine was found to be the most potent inhibitor of maize polyamine oxidase reported so far (K-i = 0.08 nM).
• Alkyl-guanidine Compounds as Potent Broad-Spectrum Antibacterial Agents: Chemical Library Extension and Biological Characterization
  作者：Carolina Pasero、Ilaria D’Agostino、Filomena De Luca、Claudio Zamperini、Davide Deodato、Giuseppina I. Truglio、Filomena Sannio、Rosita Del Prete、Teresa Ferraro、Daniela Visaggio、Arianna Mancini、Mario B. Guglielmi、Paolo Visca、Jean-Denis Docquier、Maurizio Botta

  DOI：10.1021/acs.jmedchem.8b00619

  日期：2018.10.25

  Nowadays, the increasing of multidrug-resistant pathogenic bacteria represents a serious threat to public health, and the lack of new antibiotics is becoming a global emergency. Therefore, research in antibacterial fields is urgently needed to expand the currently available arsenal of drugs. We have recently reported an alkyl-guanidine derivative (2), characterized by a symmetrical dimeric structure, as a good candidate for further developments, with a high antibacterial activity against both Gram-positive and Gram-negative strains. In this study, starting from its chemical scaffold, we synthesized a small library of analogues. Moreover, biological and in vitro pharmacokinetic characterizations were conducted on some selected derivatives, revealing notable properties: broad-spectrum profile, activity against resistant clinical isolates, and appreciable aqueous solubility. Interestingly, 2 seems neither to select for resistant strains nor to macroscopically alter the membranes, but further studies are required to determine the mode of action.