((4-Chloro-phenyl)-{[1-(4-chloro-phenyl)-meth-(E)-ylidene]-amino}-methyl)-phosphonic acid diethyl ester | 871315-39-8

• 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: ((4-Chloro-phenyl)-{[1-(4-chloro-phenyl)-meth-(E)-ylidene]-amino}-methyl)-phosphonic acid diethyl ester
• 英文别名: 1-(4-chlorophenyl)-N-[(4-chlorophenyl)-diethoxyphosphorylmethyl]methanimine
• CAS: 871315-39-8
• 化学式: C₁₈H₂₀Cl₂NO₃P
• 分子量: 400.241
• InChiKey: JDDUVSDATLAUCL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.38
• 重原子数：
  25.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  47.89
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  ((4-Chloro-phenyl)-{[1-(4-chloro-phenyl)-meth-(E)-ylidene]-amino}-methyl)-phosphonic acid diethyl ester 在 1-羟基苯并三唑 、 对甲苯磺酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 diethyl (E)-((3-(4-((2-chloro-4-fluorobenzyl)oxy)-3-methoxyphenyl)acrylamido)(4-chlorophenyl)methyl)phosphonate
  参考文献：
  名称：

  Novel α,β-unsaturated amide derivatives bearing α-amino phosphonate moiety as potential antiviral agents

  摘要：

  Based on flexible construction and broad bioactivity of ferulic acid, a series of novel alpha, beta-unsaturated amide derivatives bearing alpha-aminophosphonate moiety were designed, synthesized and systematically evaluated for their antiviral activity. Bioassay results indicated that some compounds exhibited good antiviral activities against cucumber mosaic virus (CMV) and tobacco mosaic virus (TMV) in vivo. Especially, compound g18 showed excellent curative and protective activities against CMV, with halfmaximal effective concentration (EC50) values of 284.67 mu g/mL and 216.30 mu g/mL, which were obviously superior to that of Ningnanmycin (352.08 mu g/mL and 262.53 mu g/mL). Preliminary structure-activity relationships (SARs) analysis revealed that the introduction of electron-withdrawing group at the 2-position or 4-position of the aromatic ring is favorable for antiviral activity. Present work provides a promising template for development of potential inhibitor of plant virus. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.08.048
• 作为产物：
  描述：

  4-氯苯甲醛 在 ammonium hydroxide 作用下， 生成 ((4-Chloro-phenyl)-{[1-(4-chloro-phenyl)-meth-(E)-ylidene]-amino}-methyl)-phosphonic acid diethyl ester
  参考文献：
  名称：

  Novel α,β-unsaturated amide derivatives bearing α-amino phosphonate moiety as potential antiviral agents

  摘要：

  Based on flexible construction and broad bioactivity of ferulic acid, a series of novel alpha, beta-unsaturated amide derivatives bearing alpha-aminophosphonate moiety were designed, synthesized and systematically evaluated for their antiviral activity. Bioassay results indicated that some compounds exhibited good antiviral activities against cucumber mosaic virus (CMV) and tobacco mosaic virus (TMV) in vivo. Especially, compound g18 showed excellent curative and protective activities against CMV, with halfmaximal effective concentration (EC50) values of 284.67 mu g/mL and 216.30 mu g/mL, which were obviously superior to that of Ningnanmycin (352.08 mu g/mL and 262.53 mu g/mL). Preliminary structure-activity relationships (SARs) analysis revealed that the introduction of electron-withdrawing group at the 2-position or 4-position of the aromatic ring is favorable for antiviral activity. Present work provides a promising template for development of potential inhibitor of plant virus. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.08.048

文献信息

• A simple and convenient procedure for the synthesis of 1-aminophosphonates from aromatic aldehydes
  作者：Babak Kaboudin、Khavar Moradi

  DOI：10.1016/j.tetlet.2005.03.037

  日期：2005.4

  A simple, efficient, possible industrial process has been developed for the synthesis of 1-aminophosphonic acids from simple starting materials. As described below, treatment of aromatic aldehydes with ammonia and reaction with diethyl phosphite gives diethyl N-(arylmethylene)-1-aminoaryl methylphosphonates, which can be easily hydrolyzed to diethyl 1-aminoarylmethylphosphonates. This method is easy

  已经开发了一种简单，有效，可能的工业方法，用于从简单的起始原料合成1-氨基膦酸。如下所述，用氨处理芳族醛并与亚磷酸二乙酯反应得到N-（芳基亚甲基）-1-氨基芳基甲基膦酸二乙酯，其可以容易地水解为1-氨基芳基甲基膦酸二乙酯。从简单的起始原料合成1-氨基烷基膦酸酯的方法简便，快速且产率高。
• TMSCl-Promoted Addition of Diethyl Phosphite to an Imine for the Synthesis of Bis[1-diethoxyphosphorylalkyl]amines
  作者：Babak Kaboudin、Khavar Moradi

  DOI：10.1055/s-2006-942432

  日期：——

  A convenient preparative approach for the synthesis of bis[1-diethoxyphosphorylalkyl]amines has been developed. Treatment of aromatic aldehydes with ammonia and reaction with diethyl phosphite gives diethyl aryl[(arylmethylidene)amino]methylphosphonates, which can be easily reacted with diethyl phosphite in the presence of chlorotrimethylsilane to give bis[1-diethoxyphosphor­ylalkyl]amines. This method is easy, rapid, and good-yielding for the synthesis of bis[1-diethoxyphosphorylalkyl]amines from simple starting materials.

  已开发出一种简便的制备双[1-二乙氧基膦酰基烷基]胺类化合物的方法。将芳香醛与氨反应，再与二乙基亚磷酸酯反应，得到二乙基芳基[(芳基亚甲基)氨基]甲基膦酸酯，这些化合物在氯三甲基硅烷存在下可轻松与二乙基亚磷酸酯反应，生成双[1-二乙氧基膦酰基烷基]胺。该方法简便、快速且产率高，适合从简单原料合成双[1-二乙氧基膦酰基烷基]胺。
• Synthesis and Herbicidal Activity of O,O-Diethyl N-{4-Methyl-[1,2,3]thiadiazole-5-carbonyl}- 1-amino-1-substitutedbenzyl Phosphonates
  作者：Wu Tang、Zhi-Hua Yu、De-Qing Shi

  DOI：10.1080/10426500903453326

  日期：2010.9.27

  results of a preliminary bioassay (in vitro) indicated that some of the title compounds 3 possessed moderate to good herbicidal activities against dicotyledonous plants (Brassica campestris L) at the concentration of 100 mg/L, and most of these compounds exhibited higher herbicidal activities against dicotyledonous plants (Brassica campestris L) than monocotyledonous plants (Echinochloa crus-galli). Supplemental

  在二环己基碳二亚胺 (DCC) 存在下，通过 O,O-二乙基 α-氨基取代苄基膦酸酯 1 和 4-甲基-[1,2,3] 噻二唑-5-羧酸 2 缩合合成目标化合物 3试剂。它们的结构通过光谱数据（IR、1H NMR、31P NMR、MS）和元素分析得到证实。初步生物测定（体外）结果表明，部分标题化合物3在浓度为100 mg/L时对双子叶植物（Brassica campestris L）具有中至良好的除草活性，其中大部分化合物表现出较高的除草活性对双子叶植物 (Brassica campestris L) 比单子叶植物 (Echinochloa crus-galli) 更有效。补充材料可用于本文。去出版商'
• Novel Coumarin-Containing Aminophosphonatesas Antitumor Agent: Synthesis, Cytotoxicity, DNA-Binding and Apoptosis Evaluation
  作者：Ya-Jun Li、Cai-Yi Wang、Man-Yi Ye、Gui-Yang Yao、Heng-Shan Wang

  DOI：10.3390/molecules200814791

  日期：——

  A series of novel coumarin-containing α-aminophosphonates were synthesized and evaluated for their antitumor activities against Human colorectal (HCT-116), human nasopharyngeal carcinoma (human KB) and human lung adenocarcinoma (MGC-803) cell lines in vitro. Compared with 7-hydroxy-4-methylcoumarin (4-MU), most of the derivatives showed an improved antitumor activity. Compound 8j (diethyl 1-(3-(4-methyl-2-oxo-2H-chromen-7-yloxy) propanamido)-1-phenylethyl-Phosphonate), with IC50 value of 8.68 μM against HCT-116 cell lines, was about 12 fold than that of unsubstituted parent compound. The mechanism investigation proved that 8c, 8d, 8f and 8j were achieved through the induction of cell apoptosis by G1 cell-cycle arrest. In addition, the further mechanisms of compound 8j-induced apoptosis in HCT-116 cells demonstrated that compound 8j induced the activations of caspase-9 and caspase-3 for causing cell apoptosis, and altered anti- and pro-apoptotic proteins. DNA-binding experiments suggested that some derivatives bind to DNA through intercalation. The results seem to imply the presence of an important synergistic effect between coumarin and aminophosphonate, which could contribute to the strong chelating properties of aminophosphonate moiety.

  合成了一系列含有香豆素结构的α-氨基膦酸酯类新化合物，并评估了它们对体外人结直肠癌（HCT-116）、人鼻咽癌（人KB）和人肺腺癌（MGC-803）细胞系的抗癌活性。与7-羟基-4-甲基香豆素（4-MU）相比，大多数衍生物显示出增强的抗癌活性。化合物8j（二乙基1-（3-（4-甲基-2-氧-2H-色烯-7-基氧）丙酰胺基）-1-苯乙基膦酸酯），对HCT-116细胞系的IC50值为8.68 μM，是其未取代母体化合物的约12倍。机制研究表明，8c、8d、8f和8j通过诱导G1期细胞周期阻滞来实现细胞凋亡。此外，进一步揭示了化合物8j诱导HCT-116细胞凋亡的机制，表明化合物8j通过激活caspase-9和caspase-3引起细胞凋亡，并改变抗凋亡和促凋亡蛋白。DNA结合实验表明，某些衍生物通过嵌插与DNA结合。结果似乎暗示了香豆素和氨基膦酸酯之间存在重要的协同效应，这可能有助于氨基膦酸酯部分的强螯合特性。
• Surface-Mediated Solid Phase Reactions: A Simple and New Method for the Synthesis of<i>α</i>-Aminophosphonates under Solvent-Free Conditions
  作者：Babak Kaboudin

  DOI：10.1246/cl.2001.880

  日期：2001.9

  Alumina-supported ammonium formate was found to be an efficient reagent for the synthesis of 1-aminophosphonates from aldehydes and diethyl phosphite. This method is an easy, rapid and high-yieldin...

  发现氧化铝负载的甲酸铵是从醛和亚磷酸二乙酯合成 1-氨基膦酸酯的有效试剂。这种方法是一种简单、快速和高产...