1-hydroxy-2-(1-benzylimidazol-2-yl)ethylidene-1,1-bisphosphonic acid | 131654-58-5

• 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-2-(1-benzylimidazol-2-yl)ethylidene-1,1-bisphosphonic acid
• 英文别名: 2-(1-Benzylimidazol-2-yl)-1-hydroxyethane-1,1-diphosphonic acid；2-(1-benzylimidazol-2-yl)-1-hydroxyethane-1,1-diamine；P,Pa(2)-[1-Hydroxy-2-[1-(phenylmethyl)-1H-imidazol-2-yl]ethylidene]bis[phosphonic acid]；[2-(1-benzylimidazol-2-yl)-1-hydroxy-1-phosphonoethyl]phosphonic acid
• CAS: 131654-58-5
• 化学式: C₁₂H₁₆N₂O₇P₂
• 分子量: 362.216
• InChiKey: VVTWQGRTVMQHIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  153
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-hydroxy-2-(1-benzylimidazol-2-yl)ethylidene-1,1-bisphosphonic acid 在 盐酸 、 ammonium chloride 、 sodium 作用下， 以 氨 、 水 为溶剂， 生成 2-(imidazol-2-yl)-1-hydroxyethanediphosphonic acid
  参考文献：
  名称：

  Substituted alkanediphosphonic acids and pharmaceutical use

  摘要：

  烷二膦酸，特别是具有以下公式的杂芳基烷二膦酸##STR1##其中R.sub.1是一个5-成员杂芳基基团，可能与苯或环己烯核融合，并包含作为杂原子的2到4个N原子或1个或2个N原子以及1个O或S原子，且未经取代或由较低的烷基，苯基或被较低烷基，较低烷氧基和/或卤素取代的苯基取代，或由较低烷氧基，羟基，二较低烷基氨基，较低烷硫基和/或卤素取代，并/或在能够被较低烷基，较低烷氧基和/或卤素取代的N原子处于N取代状态，R.sub.2是氢，羟基，氨基，较低烷硫基或卤素，以及它们的盐，在钙代谢上具有调节作用，并可用作治疗与钙代谢障碍相关疾病的药物。例如，通过将具有以下公式的化合物转化而得到##STR2##其中X.sub.1是功能修饰磷酸基团，X.sub.2是自由或功能修饰磷酸基团，将X.sub.1和如适当的X.sub.2转化为自由磷酸基团。

  公开号：

  US04939130A1
• 作为产物：
  描述：

  (1-苄基-1H-咪唑-2-基-)-乙酸 在 磷酸 、 三氯化磷 作用下， 以 氯苯 为溶剂， 反应 3.0h， 以52%的产率得到1-hydroxy-2-(1-benzylimidazol-2-yl)ethylidene-1,1-bisphosphonic acid
  参考文献：
  名称：

  Highly Potent Geminal Bisphosphonates. From Pamidronate Disodium (Aredia) to Zoledronic Acid (Zometa)

  摘要：

  Bisphosphonates (BP) are pyrophosphate analogues in which the oxygen in P-O-P has been replaced by a carbon, resulting in a metabolically stable P-C-P structure.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.

  DOI：

  10.1021/jm020819i

文献信息

• Method of administering bisphosphonates
  申请人：——

  公开号：US20030181421A1

  公开（公告）日：2003-09-25

  Bisphosphonates, in particular more potent N-bisphosphonates such as zoledronic acid and derivatives, can be used with satisfactory results for prolonged inhibition of bone resorption in conditions of abnormally increased bone turnover, e.g. osteoporosis, by intermittent administration, wherein the periods between bisphosphonate administrations are longer than was previously considered appropriate, e.g. a dosing interval of at least about 6 months or less frequently.

  双膦酸盐，特别是更强效的N-双膦酸盐，如左氧磷酸和衍生物，可以通过间歇性给药获得令人满意的结果，长期抑制骨质疏松等异常增加骨转换的情况中的骨吸收，例如骨质疏松症，其中双膦酸盐给药之间的间隔时间比以前认为适当的更长，例如至少大约6个月或更少频繁的给药间隔。
• Use of bisphosphonates for pain treatment
  申请人：——

  公开号：US20040063670A1

  公开（公告）日：2004-04-01

  A method for the treatment of pain, in particular antinociceptive or anti-allodynic treatment of pain, in a patient in need of such treatment, e.g. a patient with osteoporosis or osteopenia, a tumour patient or a patient suffering from an inflammatory disease, which comprises administering an effective amount of a bisphosphonate, e.g. zoledronic acid or salts or hydrates thereof, to the patient.

  一种用于治疗疼痛的方法，特别是用于需要这种治疗的患者，例如骨质疏松症或骨质疏松症患者、肿瘤患者或患有炎症性疾病的患者的镇痛或抗痛觉过敏治疗，包括向患者施用有效量的双膦酸盐，例如唑来膦酸或其盐或水合物。
• Pharmaceutical products comprising bisphosphonated
  申请人：Glausch Alexandra

  公开号：US20050119230A1

  公开（公告）日：2005-06-02

  A pharmaceutical product comprises a container containing a bisphosphonate solution, in which at least the internal surface of the container comprises a plastic material and in which the container is heat sterilisable, and which is in the form of an infusion solution preconcentrate for administration of the bisphosphonate to a patient in need of bisphosphonate treatment.

  一种药品产品包括一个容器，其中装有双磷酸盐溶液，至少该容器的内表面包括塑料材料，并且该容器可以进行热灭菌处理，该药品产品以输注溶液预浓缩物的形式存在，用于给需要双磷酸盐治疗的患者进行双磷酸盐治疗。
• PHARMACEUTICAL PRODUCTS COMPRISING BISPHOSPHONATES
  申请人：Glausch Alexandra

  公开号：US20080254089A1

  公开（公告）日：2008-10-16

  A pharmaceutical product comprises a container containing a bisphosphonate solution, in which at least the internal surface of the container comprises a plastic material and in which the container is heat sterilisable, and which is in the form of an infusion solution preconcentrate for administration of the bisphosphonate to a patient in need of bisphosphonate treatment.

  一种制药产品包括一个容器，其中包含一种双磷酸盐溶液，其中至少容器的内表面由塑料材料制成，并且容器可以进行热灭菌处理，该产品以输注溶液预浓缩物的形式提供，用于给需要双磷酸盐治疗的患者进行双磷酸盐治疗。
• BISPHOSPHONATE PRODUCT IN A CYCLOOLEFINIC POLYMER CONTAINER
  申请人：Glausch Alexandra

  公开号：US20120027818A1

  公开（公告）日：2012-02-02

  A pharmaceutical product comprises a container containing a bisphosphonate solution, in which at least the internal surface of the container comprises a plastic material and in which the container is heat sterilisable, and which is in the form of an infusion solution preconcentrate for administration of the bisphosphonate to a patient in need of bisphosphonate treatment.

  一种药物制品包括一个容器，其中装有双磷酸盐溶液，至少容器的内表面包括塑料材料，并且容器可以进行热灭菌处理，且该制品是一种输注溶液的预浓缩物，用于给需要双磷酸盐治疗的患者进行治疗。