[N-(tert-butoxycarbonyl)-N'-{N-(p-methoxybenzyl)-N-methylcarbamoyl}]-1H-pyrazole-1-carboxamidine | 1158443-10-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: [N-(tert-butoxycarbonyl)-N'-{N-(p-methoxybenzyl)-N-methylcarbamoyl}]-1H-pyrazole-1-carboxamidine
• CAS: 1158443-10-7
• 化学式: C₁₉H₂₅N₅O₄
• 分子量: 387.439
• InChiKey: IUCOAFAEWCNHCA-UHFFFAOYSA-N

物化性质

• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.87
• 重原子数：
  28.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  98.05
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2,2,2-三氟乙基胺 、 [N-(tert-butoxycarbonyl)-N'-{N-(p-methoxybenzyl)-N-methylcarbamoyl}]-1H-pyrazole-1-carboxamidine 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 25.0h， 以83%的产率得到N-tert-butoxycarbonyl-N'-(2,2,2-trifluoroethyl)-N''-(N-methyl-N-p-methoxybenzylcarbamoyl)guanidine
  参考文献：
  名称：

  Argifin; efficient solid phase total synthesis and evalution of analogues of acyclic peptide

  摘要：

  An effective solid phase synthesis of Argifin, providing subsequent access to effective synthesis of analogues, was developed in 13% overall yield, as well as elucidating structure-activity relationships. The novel acyclic peptide 18b, prepared from a synthetic intermediate of Argifin, was found to be 70 times more potent as an inhibitor of Serratia marcescens chitinases B than Argifin itself (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.02.047
• 作为产物：
  描述：

  N‐[(4‐methoxyphenyl)methyl]‐N‐methylcarbamoyl chloride 、 N-BOC-1H-吡唑-1-甲脒 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以39%的产率得到[N-(tert-butoxycarbonyl)-N'-{N-(p-methoxybenzyl)-N-methylcarbamoyl}]-1H-pyrazole-1-carboxamidine
  参考文献：
  名称：

  Argifin; efficient solid phase total synthesis and evalution of analogues of acyclic peptide

  摘要：

  An effective solid phase synthesis of Argifin, providing subsequent access to effective synthesis of analogues, was developed in 13% overall yield, as well as elucidating structure-activity relationships. The novel acyclic peptide 18b, prepared from a synthetic intermediate of Argifin, was found to be 70 times more potent as an inhibitor of Serratia marcescens chitinases B than Argifin itself (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.02.047

文献信息

• Solution-phase total synthesis of the hydrophilic natural product argifin using 3,4,5-tris(octadecyloxy)benzyl tag
  作者：Tomoyasu Hirose、Takako Kasai、Takafumi Akimoto、Ayako Endo、Akihiro Sugawara、Kazuo Nagasawa、Kazuro Shiomi、Satoshi Ōmura、Toshiaki Sunazuka

  DOI：10.1016/j.tet.2011.05.073

  日期：2011.9

  solution-phase total synthesis of argifin using 3,4,5-tris(octadecyloxy)benzyl tag as a hydrophobic protective group of carboxylic acid was developed to produce 44% overall yield for 16 linear steps. Argifin, a novel class of natural product chitinase inhibitor, is a highly water-soluble cyclic pentapeptide, so hitherto, only solid-phase synthesis techniques have been used to conveniently prepare the compound

  开发了使用3,4,5-三（十八烷基氧基）苄基标签作为羧酸的疏水性保护基的argifin溶液相全合成方法，在16个线性步骤中总收率为44％。Argifin是一类新型的天然产物几丁质酶抑制剂，是一种高度水溶性的环状五肽，因此，迄今为止，仅使用固相合成技术即可方便地制备该化合物及其衍生物。3,4,5-三（十八烷氧基）苄醇（HO-TAGa）及其酯是高度结晶的物质，具有很高的溶解度，可溶于二氯甲烷，苯，THF等极性较小的溶剂中，但不溶于极性溶剂例如甲醇和DMSO。HO-TAGa和基于Fmoc的肽合成相结合，并通过在MeOH溶液中重结晶进行简单纯化，
• 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.