(吗啉-4-基-膦酰甲基)膦酸 | 32545-75-8

• 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
• 中文名称: (吗啉-4-基-膦酰甲基)膦酸
• 英文名称: morpholin-4-ylmethylenediphosphonic acid
• 英文别名: (morpholin-4-yl)methane-1,1-diphosphonic acid；(morpholin-1-yl)methylenebisphosphonic acid；(N-morpholinomethylene)diphosphonic acid；morpholinomethylenediphosphonic acid；P,P'-morpholin-4-ylmethanediyl-bis-phosphonic acid；(morpholin-4-ylmethylene)bisphosphonic acid；Hydrogen morpholin-4-ium-4-yl(phosphono)methylphosphonate；hydroxy-[morpholin-4-ium-4-yl(phosphono)methyl]phosphinate
• CAS: 32545-75-8
• 化学式: C₅H₁₃NO₇P₂
• 分子量: 261.108
• InChiKey: KVUUQMDVROTSNI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.8
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  8

安全信息

• 海关编码：
  2934999090

反应信息

• 作为产物：
  描述：

  tetraethyl (morpholinomethylene)bisphosphonate 在 盐酸 作用下， 生成 (吗啉-4-基-膦酰甲基)膦酸
  参考文献：
  名称：

  Effects of Bisphosphonates on the Growth of Entamoeba histolytica and Plasmodium Species in Vitro and in Vivo

  摘要：

  The effects of a series of 102 bisphosphonates on the inhibition of growth of Entamoeba histolytica and Plasmodium falciparum in vitro have been determined, and selected compounds were further investigated for their in vivo activity. Forty-seven compounds tested were active (IC50 < 200 muM) versus E. histolytica growth in vitro. The most active compounds (IC50 similar to 4-9 muM) were nitrogen-containing bisphosphonates with relatively large aromatic side chains. Simple n-alkyl-1-hydroxy-1,1-bisphosphonates, known inhibitors of the enzyme farnesylpyrophosphate (FPP) synthase, were also active, with optimal activity being found with C9-C10 side chains. However, numerous other nitrogen-containing bisphosphonates known to be potent FPP synthase inhibitors, such as risedronate or pamidronate, had little or no activity. Several pyridine-derived bisphosphonates were quite active (IC50 similar to 10-20 muM), and this activity was shown to correlate with the basicity of the aromatic group, with activity decreasing with increasing pK(a) values. The activities of all compounds were tested versus a human nasopharyngeal carcinoma (KB) cell line to enable an estimate of the therapeutic index (TI). Five bisphosphonates were selected and then screened for their ability to delay the development of amebic liver abscess formation in an E. histolytica infected hamster model. Two compounds were found to decrease liver abscess formation at 10 mg/kg ip with little or no effect on normal liver mass. With P. falciparum, 35 compounds had IC50 values <200 muM in an in vitro assay. The most active compounds were also simple n-alkyl-1-hydroxy-1,1-bisphosphonates, having IC50 values around 1 muM. Five compounds were again selected for in vivo investigation in a Plasmodium berghei ANKA BALB/c mouse suppressive test. The most active compound, a C9 n-alkyl side chain containing bisphosphonate, caused an 80% reduction in parasitemia with no overt toxicity. Taken together, these results show that bisphosphonates appear to be useful lead compounds for the development of novel antiamebic and antimalarial drugs.

  DOI：

  10.1021/jm030084x

文献信息

• Synthesis and Reactivity of the New Trimethylsilyl Esters of Aminomethylenebisorganophosphorus Acids
  作者：Andrey A. Prishchenko、Mikhail V. Livantsov、Olga P. Novikova、Ludmila I. Livantsova、Ivan S. Ershov、Valery S. Petrosyan

  DOI：10.1002/hc.21100

  日期：2013.9

  trivalent organophosphorus acids containing PH and POSiMe3 fragments in the presence of trimethylsilyl trifluoromethanesulfonate as catalyst is proposed as a convenient method for the synthesis of new trimethylsilyl esters of aminomethylenebisorganophosphorus acids with three and four coordinated phosphorus. Also the new functionalized derivatives of the aminomethylenebisphosphinic acids with substituted hydroxymethyl

  提出了在三氟甲磺酸三甲基甲硅烷基酯作为催化剂存在下，含 PH 和 POSiMe3 片段的三价有机磷酸的三甲基甲硅烷基酯的相互作用，作为合成具有三和四配位磷的新型氨基亚甲基双有机磷酸三甲基甲硅烷基酯的简便方法。还合成了具有取代羟甲基部分的氨基亚甲基双次膦酸的新型官能化衍生物，并介绍了所得化合物的一些性质。
• Tris(trimethylsilyl) phosphite as key synthon for convenient synthesis of new organosilicon(phosphorus)-containing N-heterocycles
  作者：Andrey A. Prishchenko、Roman S. Alekseyev、Mikhail V. Livantsov、Olga P. Novikova、Ludmila I. Livantsova、Valery S. Petrosyan

  DOI：10.1016/j.jorganchem.2017.10.031

  日期：2018.7

  The new functionalized hydroxymethylphosphonic and methylenediphosphonic acids are synthesized via unique reaction of tris(trimethylsilyl) phosphite and N-formyl N-heterocycles, N-substituted 4-piperidones, 3-quinuclidone, and 2-adamantanone at the presence of effective catalyst – trimethylsilyl triflate under mild conditions.

  在有效催化剂–三甲基甲硅烷基三氟甲磺酸酯存在下，通过亚磷酸三（三甲基甲硅烷基）酯与N-甲酰基N-杂环，N-取代的4-哌啶酮，3-奎宁环酮和2-金刚烷酮的独特反应合成了新的官能化羟甲基膦酸和亚甲基二膦酸。在温和的条件下。
• Interactions of N-heteroalkylaminomethylenebisphosphonic acids with Cd(II) ions: Electrochemical and spectroscopic investigations
  作者：Agnieszka Dobosz、Jan Spychała、Tomasz Ptak、Gabriela Maciejewska、Ewa Chmielewska、Paweł Kafarski、Piotr Młynarz

  DOI：10.1016/j.ica.2015.05.034

  日期：2015.8

  excellent chelators for many metal ions. In this work, the coordination properties of three different aminomethylenebisphosphonates with N-substituted heteroalkyl moieties (L1, L2 and L3) and their N-pyridyl derivative (L4) toward cadmium(II) ions are described. Due to their coordination abilities over a broad range of pH, the compounds of this group are good candidates for heavy metal detoxification. To determine

  已知氨基亚甲基双膦酸酯是许多金属离子的极佳螯合剂。在这项工作中，描述了三种不同的氨基亚甲基双膦酸酯与N-取代的杂烷基部分（L1，L2和L3）及其N-吡啶基衍生物（L4）对镉（II）离子的配位性能。由于它们在很宽的pH值范围内的配位能力，因此这类化合物是重金属排毒的良好候选者。为了确定形成的氨基亚甲基双膦酸酯-镉（II）配合物的稳定性常数和配位模式，采用了四种分析方法：电位法，脉冲极谱法（DPP），核磁共振波谱法（NMR）和电喷雾电离质谱法（ESI-MS） 。进行的研究表明，配体L1 L2和L3具有相似的配位性能，Cd（II）离子在pH 2以下结合形成等摩尔配合物，在pH 6以上则形成双配合物。配体L4的行为不同，形成了六种化学计量不同的复合物：CdH4L3，CdH3L3，CdHL2，CdL2，CdH2L和Cd3H4L3。普通配合物d-青霉胺和所研究的配体之间的假设竞争曲线表明，在2-6的p
• Synthesis of N,N-disubstituted aminomethylenediphosphonates and their derivatives
  作者：A. A. Prishchenko、M. V. Livantsov、O. P. Novikova、L. I. Livantsova、I. S. Ershov、V. S. Petrosyan

  DOI：10.1134/s1070363212090265

  日期：2012.9

  as promising ligands and biologically active substances with diverse properties [1]. Previously some of the compounds of this type have been synthesized using various formamide derivatives like dialkylformamide dialkylacetals and ethoxymethylene imines [2]. Aiming to synthesize the new types of N,N-disubstituted aminomethylenediphosphonates we studied the reaction of tris(trimethylsilyl)phosphite directly

  取代的含氨基亚甲基的有机磷化合物是氨基酸和天然焦磷酸盐的类似物，作为具有多种特性的有前途的配体和生物活性物质而备受关注[1]。以前，这种类型的一些化合物是使用各种甲酰胺衍生物合成的，如二烷基甲酰胺二烷基缩醛和乙氧基亚甲基亚胺 [2]。为了合成新型 N,N-二取代氨基亚甲基二膦酸盐，我们研究了三（三甲基甲硅烷基）亚磷酸酯与最常见的 N,N-二取代甲酰胺 A 的直接反应 [3]。甲酰脯氨酸 N 三甲基甲硅烷基醚 I 我们具体通过脯氨酸甲酰化，然后用双（三甲基甲硅烷基）胺和三甲基氯硅烷作为甲硅烷基化试剂在加热到 130°C 处理得到。内政部：10。
• 1-Aminoalkane-1,1-diphosphonic acids and their salts
  申请人：Henkel & Cie G.m.b.H.

  公开号：US03979385A1

  公开（公告）日：1976-09-07

  A process for the production of 1-aminoalkane-1,1-diphosphonates of the formula ##SPC1## Wherein R.sub.1 is a member selected from the group consisting of hydrogen, lower alkyl and phenyl, R.sub.2 and R.sub. 3 are members selected from the group consisting of hydrogen, alkyl having 1 to 22 carbon atoms, cycloalkyl having 5 to 6 carbon atoms, phenyl, alkylphenyl having 7 to 18 carbon atoms, phenylalkyl having 7 to 18 carbon atoms and together with the nitrogen atom, piperidino, pyrrolidino and morpholino, and X is a member selected from the group consisting of hydrogen, alkali metal, ammonium, pyridinium, guanidinium and mono-, di-, and tri-lower-alkanol-ammonium with the proviso that at least one of R.sub.1, R.sub.2 and R.sub.3 is other than hydrogen, which consists essentially in reacting a phosphorus trihalide selected from the group consisting of phosphosus trichloride and phosphorus tribromide with a monocarboxylic acid amide of the formula ##SPC2## wherein the molecular weight of said carboxylic acid amide is over 46 and R.sub.1, R.sub.2 and R.sub. 3 have the above assigned meanings, at a temperature of from 0.degree. to 75.degree.C, subjecting the resultant reaction product to hydrolysis, and recovering said 1-aminoalkane-1,1-diphosphonates. The 1-aminoalkane-1,1-diphosphonates, some of which are novel, are capable of forming complexes with heavy metals.

  一种用于制备式为##SPC1##的1-氨基烷基-1,1-二膦酸盐的工艺，其中R.sub.1是从氢，低碳基和苯基中选择的成员，R.sub.2和R.sub.3是从氢，具有1至22个碳原子的烷基，具有5至6个碳原子的环烷基，苯基，具有7至18个碳原子的烷基苯基，具有7至18个碳原子的苯基烷基和与氮原子一起的哌啶基，吡咯烷基和吗啉基中选择的成员，X是从氢，碱金属，铵盐，吡啶盐，胍盐和单，二，三低碳醇铵盐中选择的成员，但至少有一个R.sub.1，R.sub.2和R.sub.3不是氢，其基本上包括将从磷三卤化物中选择的磷三卤化物，包括磷三氯化物和磷三溴化物与式为##SPC2##的羧酸酰胺反应，其中所述羧酸酰胺的分子量大于46且R.sub.1，R.sub.2和R.sub.3具有上述指定的含义，在0℃至75℃的温度下，将所得的反应产物进行水解，并回收所述的1-氨基烷基-1,1-二膦酸盐。这些1-氨基烷基-1,1-二膦酸盐中的一些是新颖的，能够与重金属形成配合物。