dibenzyl 2-[[bis(benzyloxy)phosphoryl]methyl]-pentanedioate | 173039-06-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: dibenzyl 2-[[bis(benzyloxy)phosphoryl]methyl]-pentanedioate
• 英文别名: dibenzyl 2-[[bis(benzyloxy)-phosphoryl]methyl]pentanedioate；dibenzyl 2-[[Bis(benzyloxy)phosphoryl]methyl]pentanedioate；Dibenzyl 2-((bis(benzyloxy)phosphoryl)methyl)pentanedioate；dibenzyl 2-[bis(phenylmethoxy)phosphorylmethyl]pentanedioate
• CAS: 173039-06-0
• 化学式: C₃₄H₃₅O₇P
• 分子量: 586.621
• InChiKey: NNMBWQCWUOTAMA-UHFFFAOYSA-N

物化性质

• 沸点：
  705.2±60.0 °C(Predicted)
• 密度：
  1.220±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  42
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  dibenzyl 2-[[bis(benzyloxy)phosphoryl]methyl]-pentanedioate 在 钯 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以to give 3(1.0 g, 90%) as a clear slightly golden viscous oil的产率得到2-(膦酰甲基)戊烷二酸
  参考文献：
  名称：

  Treatment of global and focal ischemia using naaladase inhibitors

  摘要：

  本发明涉及通过抑制NAALADase酶来治疗动物中的谷氨酸异常和相关神经组织损伤的组合物和治疗方法。所述组合物包括谷氨酸衍生的羟基膦酰衍生物化合物、酸性肽类类似物、膦酸衍生物和混合物，它们抑制NAALADase酶活性，并用于治疗由全局和局部缺血引起的谷氨酸异常。

  公开号：

  US06004946A1
• 作为产物：
  描述：

  丙烯酸苄酯 在 六甲基磷酰三胺 、 三甲基铝 作用下， 反应 32.33h， 生成 dibenzyl 2-[[bis(benzyloxy)phosphoryl]methyl]-pentanedioate
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of a Potent Inhibitor of the Neuropeptidase N-Acetylated α-Linked Acidic Dipeptidase

  摘要：

  A series of substituted phosphonate derivatives were designed and synthesized in order to study the ability of these compounds to inhibit the neuropeptidase N-acetylated alpha-linked acidic dipeptidase (NAALADase). The molecules were shown to act as inhibitors of the enzyme, with the most potent (compound 3) having a K-i of 0.275 nM. The potency of this compound is more than 1000 times greater than that of previously reported inhibitors of the enzyme. NAALADase is responsible for the catabolism of the abundant neuropeptide N-acetyl-L-aspartylglutamate (NAAG) into N-acetylaspartate and glutamate. NAAG has been proposed to be a neurotransmitter at a subpopulation of glutamate receptors; alternatively, NAAG has been suggested to act as a storage form of synaptic glutamate. As a result, inhibition of NAALADase may show utility as a therapeutic intervention in diseases in which altered levels of glutamate are thought to be involved.

  DOI：

  10.1021/jm950801q

文献信息

• NAALADase inhibitors useful as pharmaceutical compounds and compositions
  申请人：Guilford Pharmaceutical Inc.

  公开号：US06458775B1

  公开（公告）日：2002-10-01

  The present invention relates to N-Acetylated &agr;-Linked Acidic Dipeptidase (NAALADase) inhibitors enzyme activity, pharmaceutical compositions comprising such inhibitors, and methods of their use to inhibit NAALADase enzyme activity, thereby effecting neuronal activities, inhibiting angiogenesis, and treating glutamate abnormalities, compulsive disorders, prostate diseases, pain and diabetic neuropathy.

  本发明涉及N-乙酰化的α-链接酸性二肽酶（NAALADase）抑制剂酶活性，包括这种抑制剂的制药组合物，以及使用它们来抑制NAALADase酶活性，从而影响神经活动，抑制血管生成，治疗谷氨酸异常、强迫症、前列腺疾病、疼痛和糖尿病神经病变的方法。
• Methods for treating anxiety, anxiety disorders and memory impairment using naaladase inhibitors
  申请人：Guilford Pharmaceuticals Inc.

  公开号：US06228888B1

  公开（公告）日：2001-05-08

  The present invention relates to methods of using NAALADase inhibitors for treating glutamate-mediated diseases, disorders and conditions selected from the group consisting of anxiety, anxiety disorders and memory impairment.

  本发明涉及使用NAALADase抑制剂治疗由谷氨酸介导的疾病、紊乱和条件的方法，所述疾病、紊乱和条件选自焦虑、焦虑症和记忆障碍等组。
• Certain phosphonomethyl-pentanedioic acid derivatives thereof
  申请人：Guilford Pharmaceuticals Inc.

  公开号：US05672592A1

  公开（公告）日：1997-09-30

  The present disclosure relates to dipeptidase inhibitors, and more particularly, to N-Acetylated .alpha.-Linked Acidic Dipeptidase (NAALADase) enzyme inhibitors which are proposed as novel agents for the treatment of prostate cancer. NAALADase is enzyme which is a membrane-bound metalloprotease which hydrolyzes the dipeptide, N-acetyl-L-aspartate-L-glutamate (NAAG) to yield glutamate and N-acetylaspartate. The compounds of the present invention include phosphinic acid derivatives that inhibit NAALADase enzyme activity and which have been found useful for inhibiting the growth of prostate cancer cells.

  本公开涉及二肽酶抑制剂，更具体地涉及N-乙酰化α-连接的酸性二肽酶（NAALADase）酶抑制剂，其被提议为治疗前列腺癌的新型药物。NAALADase是一种膜结合的金属蛋白酶，可水解二肽酸盐N-乙酰-L-天冬酰-L-谷氨酸（NAAG）以产生谷氨酸和N-乙酰天冬酰酸。本发明的化合物包括磷酸酯衍生物，可抑制NAALADase酶活性，并已发现对抑制前列腺癌细胞的生长有用。
• Prodrugs of NAALAdase inhibitors
  申请人：Guilford Pharmaceuticals Inc.

  公开号：US06384022B1

  公开（公告）日：2002-05-07

  The present invention relates to prodrugs of NAALADase inhibitors, pharmaceutical compositions comprising the same, and methods of using the same to treat glutamate abnormalities and prostate diseases.

  本发明涉及NAALADase抑制剂的前药、包含其的药物组合物以及使用它们治疗谷氨酸异常和前列腺疾病的方法。
• Pharmaceutical compositions and methods of treating a glutamate
  申请人：Guilford Pharmaceuticals Inc.

  公开号：US06017903A1

  公开（公告）日：2000-01-25

  The present invention relates to a method of treating a glutamate abnormality and a method of effecting a neuronal activity in an animal using a NAALADase inhibitor, and a pharmaceutical composition comprising an effective amount of a NAALADase inhibitor for treating a glutamate abnormality and effecting a neuronal activity in an animal.

  本发明涉及使用NAALADase抑制剂治疗谷氨酸异常和影响动物神经活动的方法，以及包含有效量NAALADase抑制剂的药物组合物，用于治疗动物的谷氨酸异常和影响神经活动。