1-hydroxy-3-(methylamino)propylidene-1,1-bis(phosphonic acid)

• 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: 1-hydroxy-3-(methylamino)propylidene-1,1-bis(phosphonic acid)
• 英文别名: (1-Hydroxy-3-(methylamino)propane-1,1-diyl)diphosphonic acid；[1-hydroxy-3-(methylamino)-1-phosphonopropyl]phosphonic acid
• 化学式: C₄H₁₃NO₇P₂
• 分子量: 249.097
• InChiKey: APAXCKPITWPINA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.4
• 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：
  147
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-溴戊烷 、 1-hydroxy-3-(methylamino)propylidene-1,1-bis(phosphonic acid) 在 1-溴戊烷 作用下， 以52.4的产率得到ibandronate sodium monohydrate
  参考文献：
  名称：

  一种合成伊班膦酸钠的方法

  摘要：

  本发明公开了一种合成伊班膦酸钠的方法，由中间体化合物(III)与卤代正戊烷反应后再水解及酸化制备得到伊班膦酸钠；式III中R 1 为C 1～4 的烷基。本法具有反应步骤少、所用试剂毒性小、安全性好等特点。

  公开号：

  CN102093416A
• 作为产物：
  描述：

  3-甲氨基丙酸 在 儿萘酚硼烷 、 三(三甲代甲硅烷基)亚磷酸盐 、 甲醇 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以73%的产率得到1-hydroxy-3-(methylamino)propylidene-1,1-bis(phosphonic acid)
  参考文献：
  名称：

  从相应的羧酸开始一锅法合成 1-Hydroxy-1,1-bis(phosphonic acid)s

  摘要：

  通过从各种羧酸开始，报道了合成相应 1-羟基-1,1-双(膦酸) 的一锅法。这种简单方法的效率通过合成众所周知的可销售氨基羟基双（膦酸盐），例如阿仑膦酸盐或 N-甲基帕米膦酸盐而无需额外的胺功能保护/脱保护步骤来说明。

  DOI：

  10.1002/ejoc.201101094

文献信息

• 一种合成伊班膦酸钠的方法
  申请人：南京恒生制药厂

  公开号：CN102093416A

  公开（公告）日：2011-06-15

  本发明公开了一种合成伊班膦酸钠的方法，由中间体化合物(III)与卤代正戊烷反应后再水解及酸化制备得到伊班膦酸钠；式III中R 1 为C 1～4 的烷基。本法具有反应步骤少、所用试剂毒性小、安全性好等特点。
• Highly Potent Geminal Bisphosphonates. From Pamidronate Disodium (Aredia) to Zoledronic Acid (Zometa)
  作者：Leo Widler、Knut A. Jaeggi、Markus Glatt、Klaus Müller、Rolf Bachmann、Michael Bisping、Anne-Ruth Born、Reto Cortesi、Gabriela Guiglia、Heidi Jeker、Rémy Klein、Ueli Ramseier、Johann Schmid、Gerard Schreiber、Yves Seltenmeyer、Jonathan R. Green

  DOI：10.1021/jm020819i

  日期：2002.8.1

  Bisphosphonates (BP) are pyrophosphate analogues in which the oxygen in P-O-P has been replaced by a carbon, resulting in a metabolically stable P-C-P structure. Pamidronate (1b, Novartis), a second-generation BP, was the starting point for extensive SAR studies. Small changes of the structure of pamidronate lead to marked improvements of the inhibition of osteoclastic resorption potency. Alendronate (1c, MSD), with an extra methylene group in the N-alkyl chain, and olpadronate (1h, Gador), the N,N-dimethyl analogue, are about 10 times more potent than pamidronate. Extending one of the N-methyl groups of olpadronate to a pentyl substituent leads to ibandronate (1k, Roche, Boehringer-Mannheim), which is the most potent close analogue of pamidronate. Even slightly better antiresorptive potency is achieved with derivatives having a phenyl group linked via a short aliphatic tether of three to four atoms to nitrogen, the second substituent being preferentially a methyl group (e.g., 4g, 4j, 5d, or 5r). The most potent BPs are found in the series containing a heteroaromatic moiety (with at least one nitrogen atom), which is linked via a single methylene group to the geminal bisphosphonate unit. Zoledronic acid (6i), the most potent derivative, has an ED50 of 0.07 mg/kg in the TPTX in vivo assay after sc administration. It not only shows by far the highest therapeutic ratio when comparing resorption inhibition with undesired inhibition of bone mineralization but also exhibits superior renal tolerability. Zoledronic acid (6i) has thus been selected for clinical development under the registered trade name Zometa. The results of the clinical trials indicate that low doses are both efficacious and safe for the treatment of tumor-induced hypercalcemia, Paget's disease of bone, osteolytic metastases, and postmenopausal osteoporosis.
• A One-Pot Synthesis of 1-Hydroxy-1,1-bis(phosphonic acid)s Starting from the Corresponding Carboxylic Acids
  作者：Maxim Egorov、Sameh Aoun、Marc Padrines、Françoise Redini、Dominique Heymann、Jacques Lebreton、Monique Mathé-Allainmat

  DOI：10.1002/ejoc.201101094

  日期：2011.12

  various carboxylic acids, a one-pot procedure for the synthesis of the corresponding 1-hydroxy-1,1-bis(phosphonic acid)s is reported. The efficiency of this simple methodology is illustrated by synthesizing well-known marketable amino hydroxy bis(phosphonate)s such as alendronate or N-methyl pamidronate without additional steps for the protection/deprotection of the amine function.

  通过从各种羧酸开始，报道了合成相应 1-羟基-1,1-双(膦酸) 的一锅法。这种简单方法的效率通过合成众所周知的可销售氨基羟基双（膦酸盐），例如阿仑膦酸盐或 N-甲基帕米膦酸盐而无需额外的胺功能保护/脱保护步骤来说明。