tetraethyl [(4-nitrophenylamino)methyl]-1,1-bisphosphonate | 1021698-65-6

• 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: tetraethyl [(4-nitrophenylamino)methyl]-1,1-bisphosphonate
• 英文别名: tetraethyl ((4-nitrophenylamino)methylene)bisphosphonate；tetraethyl (4-nitrophenylamino)methylenebisphosphonate；tetraethyl (p-nitrophenylamino)methylenebisphosphonate；N-[bis(diethoxyphosphoryl)methyl]-4-nitroaniline
• CAS: 1021698-65-6
• 化学式: C₁₅H₂₆N₂O₈P₂
• 分子量: 424.328
• InChiKey: GHFLUTQADMDBDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tetraethyl [(4-nitrophenylamino)methyl]-1,1-bisphosphonate 在 三甲基溴硅烷 、 甲醇 作用下， 以 乙腈 为溶剂， 反应 24.5h， 以37%的产率得到[(4-nitrophenylamino)methyl]-1,1-bisphosphonic acid
  参考文献：
  名称：

  Arylamino methylene bisphosphonate derivatives as bone seeking matrix metalloproteinase inhibitors

  摘要：

  The complexity of matrix metalloproteinase inhibitors (MMPIs) design derives from the difficulty in carefully addressing their inhibitory activity towards the MMP isoforms involved in many pathological conditions. In particular, specific metalloproteinases, such as MMP-2 and MMP-9, are key regulators of the 'vicious cycle' occurring between tumor metastases growth and bone remodeling. In an attempt to devise new approaches to selective inhibitor derivatives, we describe novel bisphosphonate bone seeking MMP inhibitors (BP-MMPIs), capable to be selectively targeted and to overcome undesired side effects of broad spectrum MMPIs.In vitro activity (IC50 values) for each inhibitor was determined against MMP-2, -8, -9 and -14, because of their relevant role in skeletal development and renewal. The results show that BP-MMPIs reached IC50 values of enzymatic inhibition in the low micromolar range. Computational studies, used to rationalize some trends in the observed inhibitory profiles, suggest a possible differential binding mode in MMP-2 that explains the selective inhibition of this isoform.In addition, survival assay was conducted on J774 cell line, a well known model system used to evaluate the structure-activity relationship of BPs for inhibiting bone resorption. The resulting data, confirming the specific activity of BP-MMPIs, and their additional proved propensity to bind hydroxyapatite powder in vitro, suggest a potential use of BP-MMPIs in skeletal malignancies. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.054
• 作为产物：
  描述：

  4-硝基苯胺 、 亚磷酸二乙酯 在 ytterbium perfluorooctanoate 、 原甲酸三乙酯 作用下， 反应 0.3h， 以92%的产率得到tetraethyl [(4-nitrophenylamino)methyl]-1,1-bisphosphonate
  参考文献：
  名称：

  A facile synthesis of aminomethylene bisphosphonates catalyzed by ytterbium perfluorooctanoate under ionic liquid condition

  摘要：

  Three-component reactions of amines, triethylorthoformate and diethyl phosphite are efficiently catalyzed by ytterbium perfiuorooctanoate [Yb(PFO)(3)] in 1-butyl-3-methylimidazolium chloride ([bmim][Cl]) ionic liquid, giving the corresponding aminomethylene bisphosphonates in good yields. The catalyst can be recovered and reused for several times without any significant loss of activity. (C) 2011 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jfluchem.2011.10.005

文献信息

• Insight into the mechanism of three component condensation leading to aminomethylenebisphosphonates
  作者：Ewa Dąbrowska、Agnieszka Burzyńska、Artur Mucha、Ewa Matczak-Jon、Wanda Sawka-Dobrowolska、Łukasz Berlicki、Paweł Kafarski

  DOI：10.1016/j.jorganchem.2009.07.025

  日期：2009.11

  mechanism of the reaction remains unknown. p-Nitroaniline has been found an interesting tool to shed light on this matter. Its use allowed to separate and identify four intermediates, both non-phosphorus and phosphorus containing, and subsequently suggest the mechanism of the whole process. The acquired knowledge was helpful in explanation the route and the final product structure obtained for more

  伯胺，亚磷酸二乙酯和原甲酸三乙酯的三组分反应，然后加合物的酸水解，以良好的收率提供了N-取代的氨基亚甲基双膦酸。它用途广泛，通常用于制备具有潜在抗骨质疏松，抗菌，抗癌，抗寄生虫或除草活性的化合物。但是，反应机理仍然未知。p-硝基苯胺已被发现是阐明这一问题的有趣工具。它的使用可以分离和鉴定出四种不含磷和含磷的中间体，随后提示了整个过程的机理。获得的知识有助于解释使用4-氨基吡啶进行更复杂反应的路线和最终产物结构。毫无疑问地证明了吡啶氮原子的另外的烷基化，导致意外的N-（1-烷基吡啶-4-氨基）亚甲基双膦酸。
• A facile synthesis of aminomethylene bisphosphonates through rhodium carbenoid mediated N–H insertion reaction. Application to the preparation of powerful uranyl ligands
  作者：Delphine Lecerclé、Sandra Gabillet、Jean-Marie Gomis、Frédéric Taran

  DOI：10.1016/j.tetlet.2008.01.127

  日期：2008.3

  onto aromatic amines is described. The procedure yields aminoaryl 1,1-bisphosphonates known to display multiple biological activities. The described methodology has also been applied to the synthesis of ligands whose uranyl-binding properties have been studied.

  描述了确保双膦酸酯部分锚定在芳族胺上的直接方法。该方法产生已知显示多种生物活性的氨基芳基1，1-双膦酸酯。所描述的方法也已被用于合成其铀酰结合性质已被研究的配体。
• Facile Synthesis, Antioxidant and Antimicrobial Activity of Amino Methylene Bisphosphonates
  作者：Uma Maheswara Rao Kunda、Satheesh Krishna Balam、Bakthavatchala Reddy Nemallapudi、Syama Sundar Chereddy、Sandip Kumar Nayak、Suresh Reddy Cirandur

  DOI：10.1248/cpb.60.104

  日期：——

  A green and efficient preparation method for the amino bisphosphonates is accomplished by simple mixing and stirring of diethylphosphite, triethylorthoformate and various amines in the presence of amberlyst-15 as catalyst at room temperature under solvent free conditions. The title compounds are characterized by IR, 1H-, 13C-, 31P-NMR and mass spectra, also studied their antimicrobial and antioxidant activity.

  在室温无溶剂条件下，以琥珀酸酯-15 为催化剂，通过简单混合和搅拌亚磷酸二乙酯、正甲酸三乙酯和各种胺，实现了一种绿色高效的氨基双膦酸盐制备方法。通过红外光谱、1H-、13C-、31P-NMR 和质谱对标题化合物进行了表征，并对其抗菌和抗氧化活性进行了研究。
• Di-n-butyl ammonium chlorosulfonate as a highly efficient and recyclable ionic liquid for the synthesis of N-containing bisphosphonates
  作者：MudumalaVeeranarayana Reddy、Reddi Mohan Naidu Kalla、Lee Sang Dong、Yeon Tae Jeong

  DOI：10.1016/j.catcom.2014.12.021

  日期：2015.2

  The preparation and description of a novel secondary amine ionic liquid, di-n-butyl ammonium chlorosulfonate, is described. The di-n-butyl ammonium ionic liquid (DBA IL) was characterized by FT-IR, elemental analysis, NMR spectroscopies, and wide-angle X-ray scattering techniques, as well as thermogravimetric analysis. The DBA IL functions as an efficient, environmentally benign, and recyclable catalyst with short reaction times and high catalytic activity for the synthesis of a variety of N-containing bisphosphonates in high yields. Another merit of this ionic liquid shown that the purification of products by non-chromatographic method with good to excellent yields of the desired products. (C) 2014 Elsevier B.V. All rights reserved.
• Arylamino methylene bisphosphonate derivatives as bone seeking matrix metalloproteinase inhibitors
  作者：Marilena Tauro、Antonio Laghezza、Fulvio Loiodice、Mariangela Agamennone、Cristina Campestre、Paolo Tortorella

  DOI：10.1016/j.bmc.2013.08.054

  日期：2013.11

  The complexity of matrix metalloproteinase inhibitors (MMPIs) design derives from the difficulty in carefully addressing their inhibitory activity towards the MMP isoforms involved in many pathological conditions. In particular, specific metalloproteinases, such as MMP-2 and MMP-9, are key regulators of the 'vicious cycle' occurring between tumor metastases growth and bone remodeling. In an attempt to devise new approaches to selective inhibitor derivatives, we describe novel bisphosphonate bone seeking MMP inhibitors (BP-MMPIs), capable to be selectively targeted and to overcome undesired side effects of broad spectrum MMPIs.In vitro activity (IC50 values) for each inhibitor was determined against MMP-2, -8, -9 and -14, because of their relevant role in skeletal development and renewal. The results show that BP-MMPIs reached IC50 values of enzymatic inhibition in the low micromolar range. Computational studies, used to rationalize some trends in the observed inhibitory profiles, suggest a possible differential binding mode in MMP-2 that explains the selective inhibition of this isoform.In addition, survival assay was conducted on J774 cell line, a well known model system used to evaluate the structure-activity relationship of BPs for inhibiting bone resorption. The resulting data, confirming the specific activity of BP-MMPIs, and their additional proved propensity to bind hydroxyapatite powder in vitro, suggest a potential use of BP-MMPIs in skeletal malignancies. (C) 2013 Elsevier Ltd. All rights reserved.