(1-羟基-1-膦酰基丁基)膦酸 | 16856-53-4

• 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: (1-羟基-1-膦酰基丁基)膦酸
• 英文名称: (1-hydroxybutane-1,1-diyl)bis(phosphonic acid)
• 英文别名: 1-Hydroxy-butan-1.1-bis-phosphonsaeure；1-hydroxybutane-1,1-bisphosphonate；(1-hydroxybutylidene) bisphosphonate；1-hydroxy-1,1-butanediphosphonic acid；Phosphonic acid, (1-hydroxybutylidene)di-；(1-hydroxy-1-phosphonobutyl)phosphonic acid
• CAS: 16856-53-4
• 化学式: C₄H₁₂O₇P₂
• 分子量: 234.083
• InChiKey: RUPZRJCPTQGQRU-UHFFFAOYSA-N

物化性质

• 熔点：
  115 °C
• 沸点：
  545.4±60.0 °C(Predicted)
• 密度：
  1.794±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  135
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  丁酸 在 亚磷酸 、 甲烷磺酸 、 三氯化磷 、 水 作用下， 以90 %的产率得到(1-羟基-1-膦酰基丁基)膦酸
  参考文献：
  名称：

  新型 N-杂环、同环和脂肪族二元酸的高效合成

  摘要：

  通过各种羧酸与三氯化磷 (PC) 的反应，通过改进的简便且通用的路线合成了新的 N-杂环、同素环和脂肪族膦酸...

  DOI：

  10.1080/10426507.2023.2225670

文献信息

• Non-hydrolysable analogues of inorganic pyrophosphate as inhibitors of hepatitis C virus RNA-dependent RNA-polymerase
  作者：D. V. Yanvarev、A. N. Korovina、N. N. Usanov、S. N. Kochetkov

  DOI：10.1134/s1068162012020124

  日期：2012.3

  Inorganic pyrophosphate (PPi) is the product of the polymerization reaction catalyzed by DNA- and RNA-polymerases. A number of novel non-hydrolsable PPi analogues was synthesized; some of them inhibited the polymerization reaction catalyzed by hepatitis C virus RNA-dependent RNA-polymerase (NS5B). A new pharmacophore based on a non-hydrolysable methylenediphosphonate backbone has been developed. The

  无机焦磷酸盐 (PPi) 是由 DNA 和 RNA 聚合酶催化的聚合反应产物。合成了许多新型的不可水解的 PPi 类似物；其中一些抑制了丙型肝炎病毒 RNA 依赖性 RNA 聚合酶 (NS5B) 催化的聚合反应。已开发出基于不可水解的亚甲基二膦酸酯骨架的新药效团。介绍了 12 种双膦酸盐的构效关系分析，并说明了对 NS5B 聚合酶活性抑制至关重要的结构特征。
• Bisphosphonates derived from fatty acids are potent growth inhibitors of Trypanosoma cruzi
  作者：Sergio H. Szajnman、Brian N. Bailey、Roberto Docampo、Juan B. Rodriguez

  DOI：10.1016/s0960-894x(01)00057-9

  日期：2001.3

  We have investigated the effect of a series of bisphosphonates derived from fatty acids against Trypanosoma cruzi proliferation in in vitro assays. Some of these drugs proved to be potent inhibitors against the intracellular form of the parasite exhibiting IC50 values at the low micromolar level. As bisphosphonates are FDA clinically approved for treatment of bone resorption, their potential innocuousness makes them good candidates to control tropical diseases. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Schuelke, Ulrich, Phosphorus, Sulfur and Silicon and the Related Elements, 1990, vol. 51/52, p. 623 - 626
  作者：Schuelke, Ulrich

  DOI：——

  日期：——
• 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.
• Bisphosphonates Inhibit the Growth of <i>Trypanosoma </i><i>b</i><i>rucei</i>, <i>Trypanosoma </i><i>c</i><i>ruzi</i>, <i>Leishmania </i><i>d</i><i>onovani</i>, <i>Toxoplasma </i><i>g</i><i>ondii</i>, and <i>Plasmodium </i><i>f</i><i>alciparum</i>:  A Potential Route to Chemotherapy
  作者：Michael B. Martin、Joshua S. Grimley、Jared C. Lewis、Huel T. Heath、Brian N. Bailey、Howard Kendrick、Vanessa Yardley、Aura Caldera、Renee Lira、Julio A. Urbina、Silvia N. J. Moreno、Roberto Docampo、Simon L. Croft、Eric Oldfield

  DOI：10.1021/jm0002578

  日期：2001.3.1

  We have investigated the effects in vitro of a series of bisphosphonates on the proliferation of Trypanosoma cruzi, Trypanosoma brucei rhodesiense, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum. The results show that nitrogen-containing bisphosphonates of the type used in bone resorption therapy have significant activity against parasites, with the aromatic species having in some cases nanomolar or low-micromolar IC50 activity values against parasite replication (e.g. o-risedronate, IC50 = 220 nM for T. brucei rhodesiense; risedronate, IC50 = 490 nM for T. gondii). In T. cruzi, the nitrogen-containing bisphosphonate risedronate is shown to inhibit sterol biosynthesis at a pre-squalene level, most likely by inhibiting farnesylpyrophosphate synthase. Bisphosphonates therefore appear to have potential in treating parasitic protozoan diseases.