利塞膦酸钠杂质C

• 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: 利塞膦酸钠杂质C
• 中文别名: 利塞膦酸杂质 C
• 英文名称: 1-hydroxy-2-(4-pyridyl)ethylidene-1,1-bisphosphonic acid
• 英文别名: 4-[2-(Hydrogen phosphonato)-2-hydroxy-2-phosphonoethyl]pyridinium；hydroxy-[(1R)-1-hydroxy-1-phosphono-2-pyridin-1-ium-4-ylethyl]phosphinate
• 化学式: C₇H₁₁NO₇P₂
• 分子量: 283.114
• InChiKey: ZWHKKFUMEGWCKH-UHFFFAOYSA-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

• 作为反应物：
  描述：

  利塞膦酸钠杂质C 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 生成 1-hydroxy-2-(4-pyridinyl)-ethylidene bisphosphonic acid monosodium
  参考文献：
  名称：

  Microwave-assisted efficient synthesis of bisphosphonate libraries: a useful procedure for the preparation of bisphosphonates containing nitrogen and sulfur

  摘要：

  Microwave-assisted rapid and efficient procedure for the synthesis of bisphosphonate and their libraries is described in solvent-free medium. Bisphosphonates having nitrogen and sulfur are synthesized following this new procedure. This procedure is simple and can be useful for the generation of compound libraries of a class of bone-resorptive inhibitors such as N- and N-, S- containing bisphosphonates.

  DOI：

  10.1007/s00044-012-0153-4
• 作为产物：
  描述：

  4-吡啶乙酸盐酸盐 在 磷酸 、 三氯化磷 、 水 作用下， 以 环丁砜 为溶剂， 反应 0.43h， 生成 利塞膦酸钠杂质C
  参考文献：
  名称：

  [EN] SKELETAL REMOVAL OF BISPHOSPHONATES
  [FR] ÉLIMINATION DE BISPHOSPHONATES DANS LE SQUELETTE

  摘要：

  本文揭示了用于去除或替代骨组织中双膦酸盐的方法和组合物。

  公开号：

  WO2017210272A1

文献信息

• IMAGING PROBES, FORMULATIONS, AND USES THEREOF
  申请人：McKenna Charles E.

  公开号：US20160310621A1

  公开（公告）日：2016-10-27

  Described herein are single and dual modality bisphosphonate conjugated imaging probes. Also described herein are methods of synthesizing and using the single and dual modality bisphosphonate conjugated imaging probes.

  本文描述了单模和双模双膦酸酯共轭成像探针。本文还描述了合成和使用单模和双模双膦酸酯共轭成像探针的方法。
• SYNTHESIS OF DRUG CONJUGATES VIA REACTION WITH EPOXIDE-CONTAINING LINKERS
  申请人：McKenna Charles E.

  公开号：US20080312440A1

  公开（公告）日：2008-12-18

  The present invention relates to drug derivatives and linkers. The invention specifically relates to compounds and methods of phosphonates and linkers, that are useful as carriers for imaging agents and useful in the treatment of various bone diseases.

  本发明涉及药物衍生物和连接剂。具体涉及磷酸酯和连接剂的化合物和方法，这些化合物和方法可用作成像剂的载体，并在治疗各种骨疾病中有用。
• Novel Procedure for the Synthesis of 1‐Hydroxy‐1,1‐bisphosphonic Acids using Phenols as Medium
  作者：Divvela V. N. Srinivasa Rao、Ramesh Dandala、Garimella K. A. S. S. Narayanan、Racha Lenin、M. Sivakumaran、Andra Naidu

  DOI：10.1080/00397910701578545

  日期：2007.11

  Abstract A facile synthetic route for the synthesis of bisphosphonates in phenols is described. Preparations of some of bisphosphonates, which are presently in clinical use such as risedronic acid and alendronate sodium, are synthesized following this new, simple method. This procedure can be useful for the synthesis of this class of bone‐resorptive inhibitors in bulk quantities.

  摘要 描述了在苯酚中合成双膦酸盐的简便合成路线。一些目前用于临床的双膦酸盐制剂，如利塞膦酸和阿仑膦酸钠，是按照这种新的、简单的方法合成的。该程序可用于大量合成此类骨吸收抑制剂。
• [EN] PHOSPHONATE-DRUG CONJUGATES<br/>[FR] CONJUGUÉS PHOSPHONATE-MÉDICAMENTS
  申请人：MCKENNA CHARLES E

  公开号：WO2017132263A1

  公开（公告）日：2017-08-03

  This invention relates to drug conjugates useful for localized treatment of diseases or disorders of the middle ear and/or inner ear. Methods of treating diseases or disorders of the middle ear and/or inner ear, pharmaceutical compositions comprising the conjugates, and methods of inhibiting a Tropomyosin receptor kinase are also provided.

  本发明涉及用于局部治疗中耳和/或内耳疾病或紊乱的药物共轭物。还提供了治疗中耳和/或内耳疾病或紊乱的方法，包括该共轭物的药物组合物，以及抑制肌球蛋白受体激酶的方法。
• Eight novel metal diphosphonates based on 2-(4-pyridinyl)-1-hydroxyl-1,1-ethylidenediphosphonate: syntheses, structures, and magnetic properties
  作者：Yun-Sheng Ma、Wen-Yu Yin、Wang-Shui Cai、Ping-Zhou Zhu、Xiao-Yan Tang、Rong-Xin Yuan、Soumyajit Roy

  DOI：10.1039/c3ra43137a

  日期：——

  A systematic exploration of a series of hydrothermal reactions of 2-(4-pyridinyl)-1-hydroxyl-1,1-ethylidenediphosphonic acid (4-pyHhedpH3) with manganese, cobalt and copper salts resulted in eight new compounds, namely, Mn(4-pyHhedpH)·H2O (1), Co(4-pyHhedpH)·H2O (2), Co(4-pyHhedpH2)(C2O4)0.5(H2O)·H2O (3), Co3(4-pyHhedpH)2(C2O4)(H2O)2 (4), Cu(4-pyHhedpH2)2 (5), Cu(4-pyHhedpH) (6), CuICuII3(4-pyhedpH0.5)2 (7) and Cu3(4-pyHhedpH)2(C2O4) (8). Compounds 1 and 2 are isostructural and have ladder-like structures in which the M2(μ-O)2} (M = Mn, Co) dimer units are connected by O–P–O bridges, whereas, compound 3 has a one-dimensional chain structure, where the Co atoms are alternatively linked by C2O42− and O–P–O bridges. Compound 4 contains one chain similar to that of compound 3, while, the chains are further connected by O–P–O bridges to generate a brick-like layer. Compound 5 has a mononuclear structure in which the central Cu ion is chelated by four O atoms from two 4-pyHhedpH ligands, giving a quadrilateral planar coordination shape. Compound 6 has chain-like structures, where Cu2(μ-O)2} dimers are connected by edge-shared CuO5} square pyramids to form infinite chains. In compound 7, the Cu3(O)4} trimers are bridged by O–P–O groups to form infinite chains which are further connected by the pyridinyl groups and O–CuI–O} units to afford layers. Compound 8 has a two-dimensional structure similar to that of compound 4. The temperature-dependent magnetic susceptibility measurements show dominant antiferromagnetic interactions in compounds 1–4 and 6–8 mediated through O–P–O and/or μ-O bridges between the metal centers. The magnetization measurements reveal that compound 2 shows field-induced magnetic transition at low temperature.

  对 2-(4-吡啶基)-1-羟基-1,1-亚乙基二膦酸(4-pyHhedpH3)与锰、钴和铜盐的一系列水热反应进行了系统的探索，得到了 8 种新化合物，即 Mn(4-pyHhedpH)-H2O (1)、Co(4-pyHhedpH)-H2O (2)、Co(4-pyHhedpH2)(C2O4)0.5(H2O)-H2O (3)、Co3(4-pyHhedpH)2(C2O4)(H2O)2 (4)、Cu(4-pyHhedpH2)2 (5)、Cu(4-pyHhedpH) (6)、CuICuII3(4-pyHhedpH0.5)2 (7) 和 Cu3(4-pyHhedpH)2(C2O4) (8)。化合物 1 和 2 结构相同，具有阶梯状结构，其中M2(μ-O)2}（M = Mn、Co）二聚体单元通过 O-P-O 桥连接，而化合物 3 具有一维链状结构，其中 Co 原子通过 C2O42 桥和 O-P-O 桥交替连接。化合物 4 包含一条与化合物 3 类似的链，而这些链通过 O-P-O 桥进一步连接，形成砖状层。化合物 5 具有单核结构，其中中心的铜离子被两个 4-pyHhedpH 配体的四个 O 原子螯合，形成四边形平面配位结构。化合物 6 具有链状结构，其中Cu2(μ-O)2}二聚体由边缘共享的CuO5}方形金字塔连接，形成无限链。在化合物 7 中，Cu3(O)4}三聚体通过 O-P-O 基团桥接形成无限链，这些无限链又通过吡啶基团和O-CuI-O}单元连接成层。化合物 8 具有与化合物 4 相似的二维结构。随温度变化的磁感应强度测量结果表明，化合物 1-4 和 6-8 通过金属中心之间的 O-P-O 和/或 μ-O 桥介导了主要的反铁磁相互作用。磁化测量结果表明，化合物 2 在低温下会出现场致磁转变。