(1-羟基-1-膦酰戊基)膦酸 | 57638-03-6

• 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-膦酰戊基)膦酸
• 英文名称: 1-hydroxy-pentane-1,1-bisphosphonate
• 英文别名: (1-hydroxypentylidene)bisphosphonic acid；1-Hydroxypentane-1,1-bisphosphonate；(1-hydroxy-1-phosphonopentyl)phosphonic acid
• CAS: 57638-03-6
• 化学式: C₅H₁₄O₇P₂
• 分子量: 248.109
• InChiKey: QGLGFSYSGKZIMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  14
• 可旋转键数：
  5
• 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

• 作为反应物：
  描述：

  (1-羟基-1-膦酰戊基)膦酸 生成 (1-hydroxypentylidene)bisphosphonic acid tetramethyl ester
  参考文献：
  名称：

  Methylenebisphosphonic acid derivatives

  摘要：

  具有以下结构式（I）的新型药理活性亚甲基双膦酸盐，其中R.sup.1、R.sup.2、R.sup.3和R.sup.4独立地为直链或支链、可选择不饱和的C.sub.1 -C.sub.10烷基、可选择不饱和的C.sub.3 -C.sub.10环烷基、芳基、芳基烷基、硅基SiR.sub.3或氢，其中在结构式（I）中至少有一个基团R.sup.1、R.sup.2、R.sup.3或R.sup.4为氢，至少有一个基团不同于氢，Q.sup.1为氢、羟基、卤素、氨基NH.sub.2或OR'，其中R'为C.sub.1 -C.sub.4较低烷基或酰基，Q.sup.2为直链或支链、可选择不饱和的C.sub.1 -C.sub.10烷基、-羟基烷基或-氨基烷基，其中氧原子可以作为取代基含有一个基团，或氮原子作为取代基可含有一个或两个基团，这些基团为C.sub.1 -C.sub.4较低烷基或酰基，或氮的两个取代基与氮原子一起形成饱和、部分饱和或芳香杂环环，或Q.sup.2可选择取代和可选择不饱和的C.sub.3 - C.sub.10环烷基，该环烷基可选择通过含有1-4个C原子的直链或支链烷基与分子结合，包括立体异构体，如几何异构体和光学活性异构体，以及这些化合物的药理学可接受盐。

  公开号：

  US05438048A1
• 作为产物：
  描述：

  正戊酸 在 亚磷酸 、 甲烷磺酸 、 三氯化磷 、 水 作用下， 生成 (1-羟基-1-膦酰戊基)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

• Schuelke, Ulrich, Phosphorus, Sulfur and Silicon and the Related Elements, 1990, vol. 51/52, p. 623 - 626
  作者：Schuelke, Ulrich

  DOI：——

  日期：——
• 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.
• p-SUBSTITUTED BENZYL HYDROXYBISPHOSPHONATES: SYNTHESIS AND HYDROLYSIS
  作者：Isabelle Mallard、Jean-Marc Benech、Marc Lecouvey、Yves Leroux

  DOI：10.1080/10426500008045216

  日期：2000.7

  Several hydroxybisphosphonate benzyl esters have been synthesized for study. The effect of the benzyl substituent on the acidic hydrolysis of the phosphonic esters has also been studied.
• A Practical Synthesis of Alendronate Sodium through Counterattack Reaction
  作者：Masahiko Seki

  DOI：10.1055/s-0031-1290947

  日期：2012.5

  An efficient synthesis of alendronate sodium, an osteoporosis drug, has been developed through 'counterattack reaction' involving treatment of the respective acyl phosphonate with (MeO)(3)P and TMSBr followed by deblocking with aqueous HCl.