奥帕膦酸钠 | 63132-39-8

• 物质功能分类: 有机原料 - 有机膦化合物
• 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: 奥帕膦酸钠
• 中文别名: 奥帕膦酸
• 英文名称: olpadronate
• 英文别名: olpadronic acid；[3-(dimethylamino)-1-hydroxy-1-phosphonopropyl]phosphonic acid
• CAS: 63132-39-8
• 化学式: C₅H₁₅NO₇P₂
• 分子量: 263.124
• InChiKey: UGEPSJNLORCRBO-UHFFFAOYSA-N

物化性质

• 沸点：
  590.1±60.0 °C(Predicted)
• 密度：
  1.706±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -5.9
• 重原子数：
  15
• 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：
  139
• 氢给体数：
  5
• 氢受体数：
  8

安全信息

• 海关编码：
  2931900090

制备方法与用途

olpadronic酸是一种生物化学物质。

反应信息

• 作为反应物：
  描述：

  hexaammonium heptamolybdate tetrahydrate 、 奥帕膦酸钠 在 ammonium acetate 作用下， 以 水 为溶剂， 生成
  参考文献：
  名称：

  Shkol'nikova, L. M.; Tolkacheva, E. O.; Porai-Koshits, M. A., Koordinatsionnaya Khimiya, 1991, vol. 17, p. 249 - 254

  摘要：

  DOI：
• 作为产物：
  描述：

  N,N-二甲基-Β-丙氨酸 在 亚磷酸 、 三氯氧磷 作用下， 反应 6.5h， 生成 奥帕膦酸钠
  参考文献：
  名称：

  一类磺酸-膦酸配体的制备及其用途

  摘要：

  本发明涉及一类磺酸‑膦酸配体的制备及其用途。该类磺酸‑膦酸配体结构中包括有磺酸、季铵和膦酸基团，具体包括磺酸甜菜碱‑膦酸配体、磺酸‑唑来膦酸配体和磺酸‑利塞膦酸配体；磺酸甜菜碱‑膦酸配体分子式为：C8H21NO10P2S，分子量为384.2；磺酸‑唑来膦酸配体分子式为：C8H16O10N2P2S，分子量为394.23；磺酸‑利塞膦酸配体分子式为：C10H17O10NP2S，分子量为405.25。本发明磺酸‑膦酸配体具有极佳的亲水性，并能与多种金属元素配位。此类分子在以下两方面有重要应用：一，用于改性疏水性纳米材料，从而显著提高材料的亲水性，使其可在水相中分散；二，对肿瘤具有一定的抑制效果。

  公开号：

  CN110734460B

文献信息

• Bone mass anabolic composition comprising olpadronate
  申请人：Gador, S.A.

  公开号：US05885973A1

  公开（公告）日：1999-03-23

  The present invention provides methods for bone mass anabolic preservation or augmentation in human or other animal subjects affected by osteoporosis or other metabolic bone disorder characterized by systemic or regional bone loss, using bisphosphonates formulations, wherein the bone mass anabolic composition contains effective non-toxic doses of \x9b3-(N,N-dimethylamine)-1-hydroxypropylidene!-bisphosphonic acid or olpadronate or the monosodium or other pharmaceutically acceptable salt thereof.

  本发明提供了一种用于骨量阳性保留或增加的方法，适用于受骨质疏松症或其他代谢性骨疾病影响的人类或其他动物主体，其特征为系统性或局部骨量减少，使用双膦酸盐制剂，其中骨量阳性组合物包含有效的非毒性剂量的\x9b3-(N,N-二甲胺基)-1-羟基丙烯基!-双膦酸或奥帕龙酸或其单钠盐或其他药用可接受的盐。
• 1-Hydroxy-3-amino-alkane-1,1-diphosphonic acids and salts
  申请人：Henkel & Cie GmbH

  公开号：US04054598A1

  公开（公告）日：1977-10-18

  1-Hydroxy-3-amino-alkane-1,1-diphosphonic acids having the formula ##STR1## wherein X is a member selected from the group consisting of ##STR2## and ##STR3## wherein R.sub.1 is a member selected from the group consisting of hydrogen and alkyl having 1 to 3 carbon atoms and R.sub.2 is alkyl having 1 to 3 carbon atoms; as well as their water-soluble salts. The 1-hydroxy-3-amino-alkane-1,1-diphosphonic acids are excellent sequestering agents especially for alkaline earth metal ions. The compounds are useful in pharmaceutical preparations for treatment of disturbances of calcium or phosphate metabolism or cosmetic preparations such as toothpastes or mouthwashes for the prevention of tartar and plaque depositions.

  具有以下式子的1-羟基-3-氨基-烷基-1,1-二膦酸：##STR1## 其中X是从以下组成的成员中选择的：##STR2##和##STR3##其中R.sub.1是从氢和1至3个碳原子的烷基组成的群中选择的成员，而R.sub.2是1至3个碳原子的烷基；以及它们的水溶性盐。这些1-羟基-3-氨基-烷基-1,1-二膦酸是优秀的络合剂，特别适用于碱土金属离子。这些化合物在制药制剂中用于治疗钙或磷代谢紊乱，或在化妆品制剂中，例如牙膏或漱口水中用于预防牙垢和菌斑沉积。
• 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.
• 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.
• Synthesis and acid-base and complexing properties of amino-substituted?-hydroxyalkylidenediphosphonic acids
  作者：M. I. Kabachnik、T. Ya. Medved'、N. M. Dyaglova、Yu. M. Polikarpov、B. K. Shcherbakov、F. I. Bel'skii

  DOI：10.1007/bf00923879

  日期：1978.2