tetraethyl ((pyridine-2-ylamino)methylene)bisphosphonate | 70010-73-0

• 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: tetraethyl ((pyridine-2-ylamino)methylene)bisphosphonate
• 英文别名: tetraethyl (pyridin-2-ylamino)methylenebisphosphonate；[(2-pyridinylamino)methylidene]bisphosphonic acid tetraethylester；N-[bis(diethoxyphosphoryl)methyl]pyridin-2-amine
• CAS: 70010-73-0
• 化学式: C₁₄H₂₆N₂O₆P₂
• 分子量: 380.318
• InChiKey: ATDDKJIMVUNDTI-UHFFFAOYSA-N

物化性质

• 熔点：
  67-69 °C
• 沸点：
  518.9±50.0 °C(Predicted)
• 密度：
  1.233±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  96
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tetraethyl ((pyridine-2-ylamino)methylene)bisphosphonate 在 盐酸 作用下， 生成 ((pyridin-2-ylamino)methylene)bis(phosphonic acid)
  参考文献：
  名称：

  3-D QSAR研究双膦酸盐对利什曼原虫主要法呢基焦磷酸合酶的抑制作用。

  摘要：

  我们报告了作为利什曼原虫主要甲羟戊酸/异戊二烯生物合成途径酶，法呢基焦磷酸合酶的抑制剂的62二膦酸盐的活性。所研究的化合物具有约100 nM至约80 microM（相当于K（i）值低至10 nM）的活性（IC（50）值）。发现活性最高的化合物是唑来膦酸盐（据报道其单晶X射线结构），吡啶基-乙烷-1-羟基-1,1-双膦酸酯或吡啶甲基氨基亚甲基双膦酸酯。但是，N-脂环族氨基亚甲基双膦酸酯（如茚满膦酸酯）（N-环庚基氨基亚甲基双膦酸酯）以及含有短（n = 4、5）烷基链的脂族氨基亚甲基双膦酸酯也具有活性，IC（50）值在200-1700 nM范围内（对应于大约20-170 nM的K（i）值）。含有更长或多个（N，N-）烷基取代基的双膦酸酯是无活性的，环上缺少邻或间氮原子或具有多个卤素取代基或对氨基的芳香族化合物也是如此。为了将这些观察结果放在更定量的结构基础上，我们使用了三维定量结构-活性关系技

  DOI：

  10.1021/jm0302344
• 作为产物：
  描述：

  2-氨基吡啶 、 亚磷酸二乙酯 在 ytterbium perfluorooctanoate 、 原甲酸三乙酯 作用下， 反应 0.42h， 以75%的产率得到tetraethyl ((pyridine-2-ylamino)methylene)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

• Synthesis of new functionalized aryl and pyridyl aminomethylenebisphosphonic acids and their derivatives via silicon-assisted methodology
  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.2020.121177

  日期：2020.4

  The new convenient synthesis of functionalized aryl and pyridyl aminomethylenebisphosphonic acids and their derivatives has been developed via silicon-assisted methodology. New functionalized aminomethylenebisphosphonic acids containing pyridines moieties were obtained using unique reaction of tris(trimethylsilyl) phosphite with N-formyl aminopyridines and trimethylsilyl triflate as a catalyst under

  通过硅辅助方法已经开发了新的方便的合成官能化的芳基和吡啶基氨基亚甲基双膦酸及其衍生物的方法。利用亚磷酸三（三甲基甲硅烷基）酯与N的独特反应，获得了含有吡啶部分的新功能化氨基亚甲基双膦酸-甲酰基氨基吡啶和三氟甲磺酸三甲基甲硅烷基酯在温和条件下作为催化剂。中间体–形成的四（三甲基甲硅烷基）氨基亚甲基双膦酸酯通过用过量甲醇进一步处理而转化为目标酸。相反，在氯化锌催化剂的存在下，在加热（130℃）下，将四种组分的混合物（亚磷酸二乙基三甲基甲硅烷基酯，原甲酸三乙基酯，芳基或吡啶基胺和亚磷酸二乙基酯）合成相应的四乙基氨基亚甲基双膦酸酯。提出并详细讨论了目标物质形成的催化方案。
• Sulfonic acid functionalized hyper-cross-linked polymer: An efficient heterogeneous acid catalyst for the synthesis of N-containing bisphosphonates
  作者：Sirigireddy Sudharsan Reddy、Reddi Mohan Naidu Kalla、Anuraj Varyambath、Il Kim

  DOI：10.1016/j.catcom.2019.04.009

  日期：2019.6

  then functionalized by chlorosulfonic acid to obtain sulfonated HCBP (HCBP-SO3H) having surface area of 452 m2/g. The synthesized HCBP and HCBP-SO3H were characterized systematically by spectroscopic techniques. Further, the catalytic potential was evaluated towards the one-pot synthesis of N-containing bisphosphonates (N-BPs). To the delight, catalyst showed excellent activity in the synthesis of various

  一种新的微多孔超交联2,2'-联苯酚聚合物（氯代联苯）与770微米的良好的比表面积2 / g的合成，然后通过氯磺酸官能化以获得磺化氯代联苯（氯代联苯-SO 3 1H）具有表面积为452m 2 / g。用光谱技术对合成的HCBP和HCBP-SO 3 H进行了系统表征。此外，催化电位朝向一锅合成的评价Ñ含双膦酸盐（Ñ -bps）。令人高兴的是，催化剂在合成各种具有生物活性的芳族和杂芳族N时表现出出色的活性。-血压。值得注意的是，它可以循环使用七个周期，而其酸官能度没有任何重大损失。
• Pyridinylbisphosphonates for use as a therapeutical agent
  申请人：Leiras Oy

  公开号：US05866556A1

  公开（公告）日：1999-02-02

  The present invention relates to certain optionally ring substituted pyridinylaminomethylidene bisphosphonic acid tetralkyl esters (I) and their use for the treatment of bone diseases, such as osteolytic bone diseases due to malignancy, Paget's disease and primary and secondary osteoporosis.

  本发明涉及某些可选择环取代的吡啶基氨甲基亚膦酸四烷基酯（I）及其用于治疗骨疾病，例如由恶性肿瘤引起的溶骨性骨疾病、帕吉特病和原发性和继发性骨质疏松症的用途。
• Aminodiphosphonate apolipoprotein e modulators
  申请人：Phan Trung Hieu

  公开号：US20050075317A1

  公开（公告）日：2005-04-07

  The present invention relates to methods of use of aminodiphosphonate to modulate apolipoprotein E levels and the use of such compounds in therapy, including cardiovascular and neurological disease states.

  本发明涉及使用氨基二膦酸盐来调节载脂蛋白E水平的方法，并将这些化合物用于治疗心血管和神经系统疾病状态。
• Effects of Bisphosphonates on the Growth of <i>Entamoeba histolytica</i> and <i>Plasmodium </i>Species in Vitro and in Vivo
  作者：Subhash Ghosh、Julian M. W. Chan、Christopher R. Lea、Gary A. Meints、Jared C. Lewis、Zev S. Tovian、Ryan M. Flessner、Timothy C. Loftus、Iris Bruchhaus、Howard Kendrick、Simon L. Croft、Robert G. Kemp、Seiki Kobayashi、Tomoyoshi Nozaki、Eric Oldfield

  DOI：10.1021/jm030084x

  日期：2004.1.1

  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.