tetraethyl [(4-bromophenylamino)methyl]-1,1-bisphosphonate | 1175711-28-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: tetraethyl [(4-bromophenylamino)methyl]-1,1-bisphosphonate
• 英文别名: tetraethyl ((4-bromophenylamino)methylene)bisphosphonate；N-[bis[diethoxy(oxido)phosphaniumyl]methyl]-4-bromoaniline
• CAS: 1175711-28-0
• 化学式: C₁₅H₂₆BrNO₆P₂
• 分子量: 458.226
• InChiKey: BVDDMWLUUAOAJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 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：
  95.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tetraethyl [(4-bromophenylamino)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90%的产率得到[(4-bromophenylamino)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：

  亚磷酸二乙酯 、 4-溴苯胺 在 ytterbium perfluorooctanoate 、 原甲酸三乙酯 作用下， 反应 0.33h， 以90%的产率得到tetraethyl [(4-bromophenylamino)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

• 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.
• A microwave-assisted solvent- and catalyst-free synthesis of aminomethylene bisphosphonates
  作者：Babak Kaboudin、Soheil Alipour

  DOI：10.1016/j.tetlet.2009.05.016

  日期：2009.7

  A convenient preparative approach for the synthesis of aminomethylene bisphosphonates is developed which involves treatment of amines with triethyl orthoformate and diethyl phosphite under microwave irradiation. (C) 2009 Elsevier Ltd. 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.
• A facile synthesis of aminomethylene bisphosphonates catalyzed by ytterbium perfluorooctanoate under ionic liquid condition
  作者：Mudumala Veera Narayana Reddy、Jongsik Kim、Yeon Tae Jeong

  DOI：10.1016/j.jfluchem.2011.10.005

  日期：2012.3

  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.