1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid | 63132-38-7

• 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-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid
• 英文别名: 3-dimethylamino-1-amino-propane-1,1-diphosphonic acid；Lidadronic Acid；[1-amino-3-(dimethylamino)-1-phosphonopropyl]phosphonic acid
• CAS: 63132-38-7
• 化学式: C₅H₁₆N₂O₆P₂
• 分子量: 262.139
• InChiKey: FQBCODHKOPSNSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 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：
  115
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid 生成 奥帕膦酸钠
  参考文献：
  名称：

  1-Hydroxy-3-amino-alkane-1,1-diphosphonic acids and salts

  摘要：

  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。

  公开号：

  US04054598A1
• 作为产物：
  描述：

  二甲氨基丙腈 在 phosphorus tribromide 作用下， 以 1,4-二氧六环 、 水 、 丙酮 为溶剂， 以31%的产率得到1-amino-3-(N,N-dimethylamino)-propylidene-1,1-bisphosphonic acid
  参考文献：
  名称：

  1,3-Di-amino-alkane-1,1-diphosphonic acids and salts

  摘要：

  具有以下公式的1,3-二氨基-烷基-1,1-二膦酸：其中R.sub.1和R.sub.2是从氢和具有1至3个碳原子的烷基中选择的成员，R.sub.3是从氢和甲基中选择的成员；以及它们的水溶性盐。1,3-二氨基-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非常有用，用于治疗钙或磷代谢紊乱，或者用于化妆品制剂，如牙膏或漱口水，以预防牙垢和菌斑沉积。

  公开号：

  US04064164A1

文献信息

• 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  Bisphosphonates (BP) are pyrophosphate analogues in which the oxygen in P-O-P has been replaced by a carbon, resulting in a metabolically stable P-C-P structure.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.
• 1,3-Di-amino-alkane-1,1-diphosphonic acids and salts
  申请人：Henkel Kommanditgesellschaft auf Aktien

  公开号：US04064164A1

  公开（公告）日：1977-12-20

  1,3-Di-amino-alkane-1,1-diphosphonic acids having the formula ##STR1## wherein R.sub.1 and R.sub.2 are members selected from the group consisting of hydrogen and alkyl having 1 to 3 carbon atoms, and R.sub.3 is a member selected from the group consisting of hydrogen and methyl; as well as their water-soluble salts. The 1,3-diamino-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 mouth washes for the prevention of tartar and plaque depositions.

  具有以下公式的1,3-二氨基-烷基-1,1-二膦酸：其中R.sub.1和R.sub.2是从氢和具有1至3个碳原子的烷基中选择的成员，R.sub.3是从氢和甲基中选择的成员；以及它们的水溶性盐。1,3-二氨基-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非常有用，用于治疗钙或磷代谢紊乱，或者用于化妆品制剂，如牙膏或漱口水，以预防牙垢和菌斑沉积。
• 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。