<2-(1-methyl-3-imidazolio)-1-phosphoryl>ethylphosphonate

• 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: <2-(1-methyl-3-imidazolio)-1-phosphoryl>ethylphosphonate
• 英文别名: 2-(3-methylimidazolio)ethylidene-1,1-biphosphanic acid betaine；2-(N-methyl-imidazolium-1-yl)ethylidene-1,1-bisphosphonic acid；2-(N-methylimidazolium-1-yl)ethylidene-1,1-bisphosphonic acid；hydrogen (2-(1-methyl-1H-imidazol-3-ium-3-yl)-1-phosphonoethyl)phosphonate；[2-(1-methyl-3-imidazolio)-1-phosphoryl]ethylphosphonate；Hydroxy-[2-(3-methylimidazol-3-ium-1-yl)-1-phosphonoethyl]phosphinate
• 化学式: C₆H₁₂N₂O₆P₂
• 分子量: 270.119
• InChiKey: NXRHFOZZMMRPLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-甲基咪唑 、 vinylidene-1,1-diphosphonic acid 在 溶剂黄146 作用下， 以 水 为溶剂， 反应 3.0h， 以90%的产率得到<2-(1-methyl-3-imidazolio)-1-phosphoryl>ethylphosphonate
  参考文献：
  名称：

  亚乙烯基二膦酸与亲核试剂的反应

  摘要：

  已经表明杂环胺可以加到亚乙烯基二膦酸的活化双键上以形成具有甜菜碱结构的加合物。在脂肪胺中，只有三甲胺与亚乙烯基二膦酸反应。

  DOI：

  10.1007/bf00714446

文献信息

• [EN] LIPOPHILIC BISPHOSPHONATES AND METHODS OF USE<br/>[FR] BISPHOSPHONATES LIPOPHILES ET PROCÉDÉS D'UTILISATION
  申请人：SALK INST FOR BIOLOGICAL STUDI

  公开号：WO2016081281A1

  公开（公告）日：2016-05-26

  Disclosed herein are lipophilic bisphosphonate compounds and embodiments of a method for making the same. The compounds may inhibit FPPS and/or GGPPS enzymes. The compounds are useful for treating a disease, such as cancer, such as those with a KRAS mutation. In some embodiments, the compounds are used to prevent or treat a cancer, such as a lung cancer that has a KRAS mutation.

  本文披露了疏水性双膦酸盐化合物及其制备方法的实施例。这些化合物可以抑制FPPS和/或GGPPS酶。这些化合物可用于治疗疾病，如癌症，尤其是具有KRAS突变的癌症。在某些实施例中，这些化合物被用于预防或治疗癌症，如具有KRAS突变的肺癌。
• Reactions of vinylidenediphosphonic acid with nucleophiles
  作者：I. S. Alfer'ev、N. V. Mikhalin

  DOI：10.1007/bf00714446

  日期：1995.8

  It has been shown that heterocyclic amines can be added to the activated double bond of vinylidenediphosphonic acid to form adducts with betaine structures. Of aliphatic amines only trimethylamine reacts with vinylidenediphosphonic acid.

  已经表明杂环胺可以加到亚乙烯基二膦酸的活化双键上以形成具有甜菜碱结构的加合物。在脂肪胺中，只有三甲胺与亚乙烯基二膦酸反应。
• ——
  作者：Hagit Cohen、Vered Solomon、Ivan S. Alferiev、Eli Breuer、Asher Ornoy、Natan Patlas、Naomi Eidelman、Gerhard Hägele、Gershon Golomb

  DOI：10.1023/a:1011990129437

  日期：——

  Purpose. This work was aimed at synthesizing novel bisphosphonates (BPs) and examining them in comparison to clinically used BPs such as pamidronate and alendronate, and to tetracycline, in order to evaluate their potential as anticalcification and antiresorption agents. The correlation between the various models was examined in order to establish facile experimental models for pre-screening of potential compounds.Methods. Nitrogen-containing heterocyclic, novel BPs such as 2-(3-methylimidazolio) ethylidene-1,1-bisphosphonic acid betaine (VS-5b), 2-(2-dimethylamino-4-pyrazinio)ethylidene-1,1-bisphosphonic acid betaine (VS-6b), and 2-(2-alpha-pyridylethylthio) ethylidene-1,1-bisphosphonic acid (ISA-225), were synthesized and evaluated in comparison to clinically used BPs, in various experimental models of resorption and calcification.Results. The physicochemical properties of the novel compounds are slightly different than the BPs in clinical use: the pKa values are lower, the affinity for hydroxyapatite is lower and the solubilities of the calcium salts are higher. The anticalcification potencies of the novel compounds were high and ranked as follows: alendronate = pamidronate > VS-6b = VS-5b = ISA-225 > tetracycline. The in vivo antiresorption activity of VS-5b and VS-6b in comparison to that of the clinically employed, pamidronate, was shown to be similar and higher, respectively.Conclusions. The anticalcification activity of the novel compounds as well as that of tetracycline was lower than that of alendronate. The antiresorption activity of VS-6b was similar to that of pamidronate. A good correlation between the different models was found, enabling the facile screening of novel compounds. The activities of tetracycline and EDTA highlight the distinct behavior of BPs as "crystal poison." In addition, tetracycline was found to be a potent anticalcification agent in the ectopic calcification model.
• Chemo-Immunotherapeutic Antimalarials Targeting Isoprenoid Biosynthesis
  作者：Yonghui Zhang、Wei Zhu、Yi-Liang Liu、Hong Wang、Ke Wang、Kai Li、Joo Hwan No、Lawrence Ayong、Anmol Gulati、Ran Pang、Lucio Freitas-Junior、Craig T. Morita、Eric Oldfield

  DOI：10.1021/ml4000436

  日期：2013.4.11

  We synthesized 30 lipophilic bisphosphonates and tested them in malaria parasite killing (targeting parasite geranylgeranyl diphosphate synthase, GGPPS) and human gamma delta T cell activation (targeting human farnesyl diphosphate synthase, FPPS). Similar patterns of activity were seen in inhibiting human FPPS and Plasmodium GGPPS, with short to medium chain-length species having most activity. In cells, shorter chain-length species had low activity, due to poor membrane permeability, and longer chain length species were poor enzyme inhibitors. Optimal activity was thus seen with similar to C-10 side-chains, which have the best combination of enzyme inhibition and cell penetration. We also solved the crystal structure of one potent inhibitor, bound to FPPS. The results are of interest since they suggest the possibility of a combined chemo/immuno-therapeutic approach to antimalarial development in which both direct parasite killing and gamma delta T cell activation can be achieved with a single compound.