Benzyl-methylaminomethylen-diphosphonsaeure | 68401-12-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: Benzyl-methylaminomethylen-diphosphonsaeure
• 英文别名: [(benzyl-methyl-amino)-methylene]-1,1-bisphosphonate；N-methylbenzylaminomethane-1,1-diphosphonic acid；{[Benzyl(methyl)amino]methylene}bis(phosphonic acid)；[[benzyl(methyl)amino]-phosphonomethyl]phosphonic acid
• CAS: 68401-12-7
• 化学式: C₉H₁₅NO₆P₂
• 分子量: 295.169
• InChiKey: FOXDWSGGTHOPOM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  118
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  tetraethyl N-benzyl-N-methyl-1-aminomethylenebisphosphonate 在 盐酸 、 水 作用下， 反应 8.0h， 以14.3 g的产率得到Benzyl-methylaminomethylen-diphosphonsaeure
  参考文献：
  名称：

  N-甲基烷基氨基甲烷-1,1-二膦酸的合成及其对铜的络合物形成能力的评价（II）

  摘要：

  摘要在反应中合成了一系列具有共同叔氮原子（CH 3 –NR）的带有直链或支链烷基，环庚基或苯基烷基R取代基的N-甲基烷基氨基甲烷-1,1-二膦酸（3a-g）用原甲酸三乙酯和仲胺合成二乙基膦酸酯，然后水解，然后用甲酸和甲醛对烷基氨基甲烷-1,1-二膦酸进行Eschweiler-Clarke甲基化反应。通过pH电位法，ESI-MS光谱法，UV-Vis和EPR方法研究了3a-g对溶液中铜（II）的络合物形成能力。对3a-g的Cu（II）配合物的稳定常数的评估表明，它们依赖于R取代基施加的空间效应和电子效应的组合。已经证明，在N原子（3a，3d，3e）上具有直链或支链烷基的化合物与Cu（II）形成最稳定的配合物，最不稳定的是3f的配合物，这可以归因于所施加的空间效应通过直接与N原子连接的环庚基环 除了主要的[Cu（HL）2]配合物外，还有众所周知的{O，O}螯合结合模式，具有[O，N}供体的[Cu（HL）L]和[CuL

  DOI：

  10.1016/j.poly.2014.09.031

文献信息

• Bisphosphonate Inhibitors of <i>Toxoplasma </i><i>g</i><i>ondi </i>Growth:  In Vitro<i>,</i> QSAR, and In Vivo Investigations
  作者：Yan Ling、Gurmukh Sahota、Sarah Odeh、Julian M. W. Chan、Fausto G. Araujo、Silvia N. J. Moreno、Eric Oldfield

  DOI：10.1021/jm040132t

  日期：2005.5.1

  We have investigated the activity of 60 bisphosphonates against the replication of Toxoplasma gondii in vitro and of three of the most active compounds, in vivo. The two most active compounds found were n-alkyl bisphosphonates containing long (n = 9 or 10) hydrocarbon chains, not the nitrogen-containing species used in bone resorption therapy. The target of all of the most active bisphosphonates appears to be the isoprene biosynthesis pathway enzyme farnesyl pyrophosphate synthase (FPPS), as indicated by the correlations between T. gondii growth inhibition and FPPS (human and Leishmania major) enzyme inhibition and by the fact that a T. gondii. strain engineered to overexpress FPPS required considerably higher levels of bisphosphonates to achieve 50% growth inhibition, while the IC50 for atovaquone (which does not inhibit FPPS) remained the same in the overexpressing strain. The phosphonate inhibitor of the non-mevalonate pathway, fosmidomycin, which inhibits the enzyme 1-deoxy-xylulose-5-phosphate reductoisomerase, had no effect on T. gondii growth. To investigate structure-activity relationships (SARs) in more detail, we used two three-dimensional quantitative SAR methods: comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), to investigate all 60 bisphosphonates. Both the CoMFA and CoMSIA models indicated a 60-70% contribution from steric interactions and a 30-40% contribution from electrostatic interactions and using four N = 55 training sets for each method, we found on average between a factor of 2 and 3 error in IC50 prediction. The three most active compounds found in vitro were tested in vivo in a Smith-Webster mouse model and the two most active bisphosphonates were found to provide up to an 80% protection from death, a considerable improvement over that found previously with nitrogen-containing bisphosphonates. This effect may originate in the much higher therapeutic indices of these alkyl bisphosphonates, as deduced from in vitro assays using LD50 values for growth inhibition of a human cell line. Overall, these results indicate that alkyl bisphosphonates are promising compounds for further development as agents against Toxoplasma gondii growth, in vivo.
• Maier, Ludwig, Phosphorus and Sulfur and the Related Elements, 1981, vol. 11, p. 311 - 322
  作者：Maier, Ludwig

  DOI：——

  日期：——
• MAIER, L., PHOSPH. AND SULFUR, 1981, 11, N 3, 311-322
  作者：MAIER, L.

  DOI：——

  日期：——
• Synthesis of N-methyl alkylaminomethane-1,1-diphosphonic acids and evaluation of their complex-formation abilities towards copper(II)
  作者：Barbara Kurzak、Waldemar Goldeman、Magdalena Szpak、Ewa Matczak-Jon、Anna Kamecka

  DOI：10.1016/j.poly.2014.09.031

  日期：2015.1

  can be attributed to the steric effect imposed by cycloheptyl ring attached directly to the N atom. In addition to the main [Cu(HL) 2 ] complexes, with well-known O, O} chelating binding mode, [Cu(HL)L] and [CuL 2 ] species with the O, N} donor set, protonated dinuclear [Cu 2 H x L 3 ] ( x = 4, 5, 6) species have been detected in all studied systems. The nitrogen coordination in the [Cu(HL)L] and

  摘要在反应中合成了一系列具有共同叔氮原子（CH 3 –NR）的带有直链或支链烷基，环庚基或苯基烷基R取代基的N-甲基烷基氨基甲烷-1,1-二膦酸（3a-g）用原甲酸三乙酯和仲胺合成二乙基膦酸酯，然后水解，然后用甲酸和甲醛对烷基氨基甲烷-1,1-二膦酸进行Eschweiler-Clarke甲基化反应。通过pH电位法，ESI-MS光谱法，UV-Vis和EPR方法研究了3a-g对溶液中铜（II）的络合物形成能力。对3a-g的Cu（II）配合物的稳定常数的评估表明，它们依赖于R取代基施加的空间效应和电子效应的组合。已经证明，在N原子（3a，3d，3e）上具有直链或支链烷基的化合物与Cu（II）形成最稳定的配合物，最不稳定的是3f的配合物，这可以归因于所施加的空间效应通过直接与N原子连接的环庚基环 除了主要的[Cu（HL）2]配合物外，还有众所周知的O，O}螯合结合模式，具有[O，N}供体的[Cu（HL）L]和[CuL