N‐[(4‐methoxyphenyl)methyl]‐N‐methylcarbamoyl chloride | 55245-86-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N‐[(4‐methoxyphenyl)methyl]‐N‐methylcarbamoyl chloride
• 英文别名: N-(p-methoxybenzyl)-N-methylcarbamoyl chloride；Carbamic chloride, N-[(4-methoxyphenyl)methyl]-N-methyl-；N-[(4-methoxyphenyl)methyl]-N-methylcarbamoyl chloride
• CAS: 55245-86-8
• 化学式: C₁₀H₁₂ClNO₂
• 分子量: 213.664
• InChiKey: JNZGYVRWVDGXKR-UHFFFAOYSA-N

物化性质

• 沸点：
  345.3±25.0 °C(Predicted)
• 密度：
  1.196±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N‐[(4‐methoxyphenyl)methyl]‐N‐methylcarbamoyl chloride 在 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 mineral oil 为溶剂， 反应 16.17h， 生成 tert‐butyl N‐({[8‐({8‐[({[(tert‐butoxy)carbonyl]imino}({[(4‐methoxyphenyl)methyl](methyl)carbamoyl}amino)methyl)amino]octyl}amino)octyl]amino}({[(4‐methoxyphenyl)methyl](methyl)carbamoyl}amino)methylidene)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：

  N-(4-甲氧基亚苄基)甲胺 在 sodium tetrahydroborate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 N‐[(4‐methoxyphenyl)methyl]‐N‐methylcarbamoyl chloride
  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

• Antibacterial alkylguanidino ureas: Molecular simplification approach, searching for membrane-based MoA
  作者：Ilaria D'Agostino、Claudia Ardino、Giulio Poli、Filomena Sannio、Massimiliano Lucidi、Federica Poggialini、Daniela Visaggio、Enrico Rango、Silvia Filippi、Elena Petricci、Paolo Visca、Lorenzo Botta、Jean-Denis Docquier、Elena Dreassi

  DOI：10.1016/j.ejmech.2022.114158

  日期：2022.3

  Health challenge. New chemical entities with innovative Modes of Action (MoAs) are thus desirable. We recently reported the development of a novel class of broad-spectrum bactericidal agents, the AlkylGuanidino Ureas (AGU). Due to their polycationic structure, they likely target bacterial membranes. In order to better understand their MoA, we synthesized a library of AGU derivatives by structural simplification

  抗菌素耐药性 (AMR) 的快速上升代表了全球公共卫生的一项重大挑战。因此，需要具有创新作用模式 (MoA) 的新化学实体。我们最近报道了一类新型广谱杀菌剂——烷基胍脲（AGU）的开发。由于它们的聚阳离子结构，它们可能以细菌膜为目标。为了更好地了解它们的 MoA，我们通过对选定的命中化合物进行结构简化，合成了一个 AGU 衍生物库，并通过分析和计算技术开发了基于膜模型的特定测定。基于细胞的测定提供了实验证据，表明 AGU 破坏细菌膜而不显示溶血行为。因此，
• Carbamoyl Triazoles, Known Serine Protease Inhibitors, Are a Potent New Class of Antimalarials
  作者：Matthew McConville、Jorge Fernández、Íñigo Angulo-Barturen、Noemi Bahamontes-Rosa、Lluis Ballell-Pages、Pablo Castañeda、Cristina de Cózar、Benigno Crespo、Laura Guijarro、María Belén Jiménez-Díaz、Maria S. Martínez-Martínez、Jaime de Mercado、Ángel Santos-Villarejo、Laura M. Sanz、Micol Frigerio、Gina Washbourn、Stephen A. Ward、Gemma L. Nixon、Giancarlo A. Biagini、Neil G. Berry、Michael J. Blackman、Félix Calderón、Paul M. O’Neill

  DOI：10.1021/acs.jmedchem.5b00434

  日期：2015.8.27

  filtered the TCAMS through a variety of criteria and reported 47 series containing a total of 522 compounds. From this enhanced set, we identified the carbamoyl triazole TCMDC-134379 (1), a known serine protease inhibitor, as an excellent starting point for SAR profiling. Lead optimization of 1 led to several molecules with improved antimalarial potency, metabolic stabilities in mouse and human liver microsomes

  对 GSK 公司收集的约 190 万种化合物针对恶性疟原虫( Pf ) 进行筛选后，发现了近 14000 种有效命中，现在称为 Tres Cantos Antimalarial Set (TCAMS)。Calderon 等人的后续工作。通过各种标准对 TCAMS 进行聚类和计算过滤，并报告了 47 个系列，共包含 522 种化合物。从这个增强的集合中，我们确定了氨基甲酰三唑 TCMDC-134379 ( 1 )，一种已知的丝氨酸蛋白酶抑制剂，作为 SAR 分析的一个很好的起点。1的先导优化导致几种分子具有改善的抗疟效力、小鼠和人肝微粒体中的代谢稳定性以及可接受的细胞毒性特征。类似物图44在Pf感染的SCID小鼠模型中显示出有效的体外活性(IC 50 = 10nM)和口服活性， ED 50分别为100和ED 90在100和150mg kg -1之间。呈现的结果鼓励进一步研究以确定这些高活性化合物的目标。
• FR2234293
  申请人：——

  公开号：——

  公开（公告）日：——
• β-Lactam Derivatives as Inhibitors of Human Cytomegalovirus Protease
  作者：Christiane Yoakim、William W. Ogilvie、Dale R. Cameron、Catherine Chabot、Ingrid Guse、Bruno Haché、Julie Naud、Jeff A. O'Meara、Raymond Plante、Robert Déziel

  DOI：10.1021/jm980131z

  日期：1998.7.1

  The development of novel monobactam inhibitors of HCMV protease incorporating a carbon side chain at C-4 and a urea function at N-1 is described. Substitution with small groups at the C-3 position of the beta-lactam ring gave an increase in enzymatic activity and in stability; however, a lack of selectivity against other serine proteases was noted. The use of both tri- and tetrasubstituted urea functionalities gave effective inhibitors of HCMV protease. Benzyl substitution of the urea moiety was beneficial, especially when strong electron-withdrawing groups where attached at the para position. Modest antiviral activity was found in a plaque reduction assay.
• Argifin; efficient solid phase total synthesis and evalution of analogues of acyclic peptide
  作者：Toshiaki Sunazuka、Akihiro Sugawara、Kanami Iguchi、Tomoyasu Hirose、Kenichiro Nagai、Yoshihiko Noguchi、Yoshifumi Saito、Tsuyoshi Yamamoto、Hideaki Ui、Hiroaki Gouda、Kazuro Shiomi、Takeshi Watanabe、Satoshi Ōmura

  DOI：10.1016/j.bmc.2009.02.047

  日期：2009.4

  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.