octadecyl-1-hydroxy-1,1-bisphosphonate | 2809-25-8

• 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
• 英文名称: octadecyl-1-hydroxy-1,1-bisphosphonate
• 英文别名: (1-Hydroxy-1-phosphono-octadecyl)-phosphonic acid；(1-hydroxy-1-phosphonooctadecyl)phosphonic acid
• CAS: 2809-25-8
• 化学式: C₁₈H₄₀O₇P₂
• 分子量: 430.459
• InChiKey: PRYRPDIVSJIODL-UHFFFAOYSA-N

物化性质

• 沸点：
  614.0±65.0 °C(Predicted)
• 密度：
  1.190±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  27
• 可旋转键数：
  18
• 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：

  硬脂酸 在 亚磷酸 、 三氯化磷 、 水 作用下， 生成 octadecyl-1-hydroxy-1,1-bisphosphonate
  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

文献信息

• [EN] METHOD FOR THE SYNTHESIS OF ALKANE-1-HYDROXY-1,1-DIPHOSPHONIC ACID<br/>[FR] PROCÉDÉ DE SYNTHÈSE DE L'ACIDE ALCANE-1-HYDROXY-1,1-DIPHOSPHONIQUE
  申请人：STRAITMARK HOLDING AG

  公开号：WO2015059287A1

  公开（公告）日：2015-04-30

  The present invention is related to a new method for the synthesis of alkane-1-hydroxy-,1-diphosphonic acid or its salts which includes the steps of -reacting tetraphosphorus hexaoxide and a carboxylic acid under controlled reaction conditions; -hydrolyzing the formed alkane-1-hydroxy-1,1-diphosphonic acid condensates to form alkane-1-hydroxy-1,1-diphosphonic acid; -precipitating the alkane-1-hydroxy-1,1-diphosphonic acid through the use of a suitable solvent; -filtering the alkane-1-hydroxy-1,1-diphosphonic acid and recovering the mother liquor and the suitable solvent.1 The process according to the method of the present invention is highly controllable and is further characterized by a high selectivity.

  本发明涉及一种合成烷基-1-羟基-1,1-二膦酸或其盐的新方法，包括以下步骤：-在控制的反应条件下，将四磷六氧化物和羧酸反应；-水解形成的烷基-1-羟基-1,1-二膦酸缩聚物以形成烷基-1-羟基-1,1-二膦酸；-通过使用适当的溶剂沉淀烷基-1-羟基-1,1-二膦酸；-过滤烷基-1-羟基-1,1-二膦酸并回收母液和适当的溶剂。根据本发明的方法，该过程具有高度可控性，并且具有高选择性。
• Electrically conductive coating composition
  申请人：LION CORPORATION

  公开号：EP0292190A2

  公开（公告）日：1988-11-23

  An electrically conductive coating composition containing a metallic powder, a thermoplastic and/or thermosetting resin, and a diphosphonic acid derivative having the formula (I): wherein R represents an alkyl having 3 to 21 carbon atoms or an aryl having 6 to 14 carbon atoms and M¹ to M⁴ independently represent hydrogen or a cation.

  一种导电涂料组合物，含有金属粉末、热塑性和/或热固性树脂以及具有式 (I) 的二膦酸衍生物： 其中 R 代表具有 3 至 21 个碳原子的烷基或具有 6 至 14 个碳原子的芳基，M¹ 至 M⁴ 独立地代表氢或阳离子。
• 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.
• US4020091A
  申请人：——

  公开号：US4020091A

  公开（公告）日：1977-04-26