奈立膦酸钠盐 | 80729-79-9

• 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: 奈立膦酸钠盐
• 英文名称: sodium neridronate
• 英文别名: neridronate sodium；sodium;(6-amino-1-hydroxy-1-phosphonohexyl)-hydroxyphosphinate
• CAS: 80729-79-9
• 化学式: C₆H₁₆NO₇P₂*Na
• 分子量: 299.133
• InChiKey: MHYULJPRWPTMTD-UHFFFAOYSA-M

物化性质

• 熔点：
  263-266° (hemihydrate)
• 溶解度：
  可微溶于水

计算性质

• 辛醇/水分配系数(LogP)：
  -4.12
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  164
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  奈立膦酸钠盐 在 palladium on activated charcoal sodium hydroxide 、 氢气 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 54.0h， 生成 6-N-(3,4-dihydroxybenzoyl)aminohexane-1-hydroxy-1,1-bisphosphonic acid disodium
  参考文献：
  名称：

  新的潜在螯合剂的合成：用于金属中毒治疗的儿茶酚-双膦酸盐缀合物

  摘要：

  为了寻求更好的螯合治疗药物来治疗铁、铝或锕系元素中毒，合成了三个新系列的与儿茶酚结合的双膦酸盐。© 2004 Wiley Periodicals, Inc. 杂原子化学 15:251–257, 2004; 在线发表于 Wiley InterScience (www.interscience.wiley.com)。DOI 10.1002/hc.20013

  DOI：

  10.1002/hc.20013
• 作为产物：
  描述：

  sodium hydroxide 在 亚磷酸 、 三氯化磷 、 水 作用下， 以 乙腈 为溶剂， 反应 15.0h， 以44.4%的产率得到奈立膦酸钠盐
  参考文献：
  名称：

  WO2008/4000

  摘要：

  公开号：

文献信息

• Microwave-assisted synthesis of nitrogen-containing 1-hydroxymethylenebisphosphonate drugs
  作者：Dana A. Mustafa、Boris A. Kashemirov、Charles E. McKenna

  DOI：10.1016/j.tetlet.2011.02.058

  日期：2011.5

  A simple, rapid one-pot synthesis of heterocyclic (risedronate, zoledronate) and aminoalkyl (pamidronate, alendronate, neridronate) bisphosphonate drugs using microwave irradiation is presented. Good yields of product are achieved within 20 min, in contrast to conventional synthesis, which typically requires a day or longer.

  提出了一种简单，快速的一锅法，用微波辐射合成杂环（雷司膦酸酯，唑来膦酸酯）和氨基烷基（帕米膦酸酯，阿仑膦酸酯，神经磷酸酯）双膦酸酯药物。与通常需要一天或更长时间的常规合成相比，在20分钟内可实现良好的产品收率。
• NOVEL PROCESS
  申请人：Gore Vinayak G.

  公开号：US20090198062A1

  公开（公告）日：2009-08-06

  The present invention relates to a process for the preparation of bisphosphonic acids and salts thereof, in particular monosodium salts thereof. The invention also relates to the conversion of the bisphosphonic acids to their sodium salts using an aqueous-organic solvent system. The present invention further relates to the conversion of variable hydrate forms of risedronic acid monosodium salt into a pharmaceutically acceptable hemipentahydrate form by crystallization using an aqueous-organic solvent system.

  本发明涉及一种制备双膦酸及其盐，尤其是单偏磷酸钠盐的方法。本发明还涉及使用水-有机溶剂体系将双膦酸转化为其钠盐的方法。本发明还涉及使用水-有机溶剂体系通过结晶将不同水合形式的瑞舒地尼酸单偏磷酸钠盐转化为药学上可接受的半五水合物形式的方法。
• POLYMORPH OF SODIUM NERIDRONATE AND PREPARATION PROCESS THEREOF
  申请人：ABIOGEN PHARMA S.P.A.

  公开号：US20190308999A1

  公开（公告）日：2019-10-10

  The present invention relates to a novel crystalline hemihydrate polymorph of neridronic acid sodium salt, and a novel process for the preparation thereof comprising the steps of: 1) dissolving solid sodium neridronate in any crystalline form in water, at a temperature in the range from 70 to 90° C., to obtain an aqueous solution of sodium neridronate; 2) adding a solvent selected from the group consisting in ethanol, 1-propanol, and 2-propanol to the aqueous solution obtained from step (1), so that the final water:solvent volume ratio is in the range from 1:0.5 to 1:1, thus obtaining a suspension; 3) placing the suspension obtained from step (2) under mechanical stirring, at a temperature in the range from 60 to 95° C.; 4) recovering the crystalline hemihydrate form F of sodium neridronate formed in the previous step (3). The crystalline hemihydrate form F of sodium neridronate, particularly stable, may be employed in the preparation of solid oral pharmaceutical forms for use in the treatment of musculoskeletal and calcium metabolism disorders.

  本发明涉及一种新的结晶半水合物多形式的奈力昔酸钠盐，以及一种新的制备方法，包括以下步骤：1）将任何晶体形式的固态奈力昔酸钠溶解在水中，在70至90℃的温度范围内，以获得奈力昔酸钠的水溶液；2）向步骤（1）中获得的水溶液中加入从乙醇、1-丙醇和2-丙醇中选择的溶剂，使最终的水：溶剂体积比在1：0.5至1：1的范围内，从而获得悬浮液；3）将从步骤（2）中获得的悬浮液置于机械搅拌下，在60至95℃的温度范围内；4）回收在前一步骤（3）中形成的奈力昔酸钠结晶半水合物F形式。特别稳定的奈力昔酸钠结晶半水合物F形式可用于制备固体口服制剂，用于治疗肌肉骨骼和钙代谢紊乱。
• [EN] PROCESS FOR THE PREPARATION OF THE POLYMORPH F OF SODIUM NERIDRONATE<br/>[FR] PROCÉDÉ DE PRÉPARATION DU POLYMORPHE F DE NERIDRONATE DE SODIUM
  申请人：ABIOGEN PHARMA SPA

  公开号：WO2020245780A1

  公开（公告）日：2020-12-10

  The present invention relates to a new process for the preparation of the crystalline polymorph of sodium neridronate in form hemihydrate F, comprising the following steps: a) reacting the 6-aminohexanoic acid with a mixture of phosphorous acid and methanesulfonic acid at a temperature in the range from 60 to 80°C, under stirring, until a clear solution is obtained; b) adding phosphorus trichloride to said solution of step (a) under stirring at a temperature in the range of 60 to 80°C; c) diluting with water the reaction mixture obtained from the previous step (b) and heating said water diluted mixture at a temperature in the range from 80 to 120°C; d) cooling the heated mixture obtained in step (c) up to room temperature, diluting it with water, then slowly adding an aqueous sodium hydroxide solution up to a pH in the range from 4.2 to 4.6, to obtain a neutralized solution; e) bringing the neutralized solution of step (d) up to a temperature of about 70°C, then subjecting it to a temperature increase in the range from 70 to 140°C, until evaporation of at least 70% of the initial volume of the neutralized solution of step (d), thus obtaining a suspension to be kept under stirring for at least 1 hour; f) cooling the suspension of step (e) up to a temperature in the range from around 5 to 25°C; and g) recovering the crystalline sodium neridronate in hemihydrate form F by filtering the suspension of the previous step (f). The process is particularly simple, scalable and environmentally sustainable.

  本发明涉及一种制备半水合物F形态的晶态聚合物钠奈立德酸的新工艺，其包括以下步骤：a）将6-氨基己酸与磷酸和甲烷磺酸混合物在60至80℃的温度下搅拌反应，直到得到清澈的溶液；b）在60至80℃的温度下将三氯化磷加入步骤（a）中的溶液中，并在搅拌下反应；c）用水稀释前一步骤（b）中得到的反应混合物，并将该稀释的混合物加热至80至120℃的温度；d）将在步骤（c）中加热的混合物冷却至室温，用水稀释后，缓慢加入水溶性氢氧化钠溶液，直到pH值在4.2至4.6范围内，以获得中和溶液；e）将步骤（d）中的中和溶液升温至约70℃，然后将其在70至140℃范围内升温，直到蒸发至少70％的步骤（d）中初始体积的混合物，从而获得悬浮液，该悬浮液需在搅拌下保持至少1小时；f）将步骤（e）中的悬浮液冷却至约5至25℃的温度；g）通过过滤步骤（f）中的悬浮液，回收晶态钠奈立德酸的半水合物F形态。该工艺特别简单、可扩展且环保。
• Compositions including polymerizable bisphosphonic acids and methods
  申请人：——

  公开号：US20040206932A1

  公开（公告）日：2004-10-21

  The present invention is directed to compositions containing one or more polymerizable bisphosphonic acids and optionally one or more additional polymerizable components.

  本发明涉及含有一种或多种可聚合双磷酸盐以及可选的一种或多种附加可聚合组分的组合物。