利塞膦酸杂质 | 1035438-80-2

• 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: 利塞膦酸杂质
• 英文名称: risedronic acid-d4
• 英文别名: 1-hydroxy-2-([2,4,5,6-2H4]-pyridin-3-yl)ethylidene-1,1-bisphosphonic acid；Risedronic Acid-d4 (Major)；[1-hydroxy-1-phosphono-2-(2,4,5,6-tetradeuteriopyridin-3-yl)ethyl]phosphonic acid
• CAS: 1035438-80-2
• 化学式: C₇H₁₁NO₇P₂
• 分子量: 287.083
• InChiKey: IIDJRNMFWXDHID-RZIJKAHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  148
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-吡啶-d4-乙酸 在 亚磷酸 、 三氯氧磷 、 盐酸 作用下， 以 甲苯 为溶剂， 反应 11.0h， 以65%的产率得到利塞膦酸杂质
  参考文献：
  名称：

  NMR Investigations of the Static and Dynamic Structures of Bisphosphonates on Human Bone:  a Molecular Model

  摘要：

  We report the results of an investigation of the binding of a series of bisphosphonate drugs to human bone using H-2, C-13, N-15, and P-31 nuclear magnetic resonance spectroscopy. The P-31 NMR results show that the bisphosphonate groups bind irrotationally to bone, displacing orthophosphate from the bone mineral matrix. Binding of pamidronate is well described by a Langmuir-like isotherm, from which we deduce an similar to 30-38 angstrom(2) surface area per pamidronate molecule and a Delta G = -4.3 kcal mol(-1). TEDOR of [C-13(3), N-15] pamidronate on bone shows that the bisphosphonate binds in a gauche [N-C(1)] conformation. The results of P-31 as well as N-15 shift and cross-polarization measurements indicate that risedronate binds weakly, since it has a primarily neutral pyridine side chain, whereas zoledronate (with an imidazole ring) binds more strongly, since the ring is partially protonated. The results of H-2 NMR measurements of side-chain 2 H-labeled pamidronate, alendronate, zoledronate, and risedronate on bone show that all side chains undergo fast but restricted motions. In pamidronate, the motion is well simulated by a gauche(+)/gauche(-) hopping motion of the terminal -CH2-NH3+ group, due to jumps from one anionic surface group to another. The results of double-cross polarization experiments indicate that the NH3+-terminus of pamidronate is close to the bone mineral surface, and a detailed model is proposed in which the gauche side-chain hops between two bone PO43- sites.

  DOI：

  10.1021/ja0759949