2-(Bis-benzyloxy-phosphorylmethyl)-succinic acid dibenzyl ester | 173039-07-1

• 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: 2-(Bis-benzyloxy-phosphorylmethyl)-succinic acid dibenzyl ester
• 英文别名: Dibenzyl 2-[bis(phenylmethoxy)phosphorylmethyl]butanedioate
• CAS: 173039-07-1
• 化学式: C₃₃H₃₃O₇P
• 分子量: 572.595
• InChiKey: GRRDZIPVSFWBKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  41
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 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：

  2-(Bis-benzyloxy-phosphorylmethyl)-succinic acid dibenzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 水 为溶剂， 生成 1-Phosphonopropane-2,3-dicarboxylic acid
  参考文献：
  名称：

  Design and Pharmacological Activity of Phosphinic Acid Based NAALADase Inhibitors

  摘要：

  A novel series of phosphinic acid based inhibitors of the neuropeptidase NAALADase are described in this work. This series of compounds is the most potent series of inhibitors of the enzyme described to date. In addition, we have shown that these compounds are protective in animal models of neurodegeneration. Compound 34 significantly prevented neurodegeneration in a middle cerebral artery occlusion model of cerebral ischemia. In addition, in the chronic constrictive mc del of neuropathic pain, compound 34 significantly attenuated the hypersensitivity observed with saline-treated animals. These data suggest that NAALADase inhibition may provide a new approach for the treatment of both neurodegenerative disorders and peripheral neuropathies.

  DOI：

  10.1021/jm0001774
• 作为产物：
  描述：

  衣康酸 在 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-(Bis-benzyloxy-phosphorylmethyl)-succinic acid dibenzyl ester
  参考文献：
  名称：

  Design and Pharmacological Activity of Phosphinic Acid Based NAALADase Inhibitors

  摘要：

  A novel series of phosphinic acid based inhibitors of the neuropeptidase NAALADase are described in this work. This series of compounds is the most potent series of inhibitors of the enzyme described to date. In addition, we have shown that these compounds are protective in animal models of neurodegeneration. Compound 34 significantly prevented neurodegeneration in a middle cerebral artery occlusion model of cerebral ischemia. In addition, in the chronic constrictive mc del of neuropathic pain, compound 34 significantly attenuated the hypersensitivity observed with saline-treated animals. These data suggest that NAALADase inhibition may provide a new approach for the treatment of both neurodegenerative disorders and peripheral neuropathies.

  DOI：

  10.1021/jm0001774

文献信息

• Design, Synthesis, and Biological Activity of a Potent Inhibitor of the Neuropeptidase N-Acetylated α-Linked Acidic Dipeptidase
  作者：Paul F. Jackson、Derek C. Cole、Barbara S. Slusher、Susan L. Stetz、Laurie E. Ross、Bruce A. Donzanti、Diane Amy Trainor

  DOI：10.1021/jm950801q

  日期：1996.1.1

  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.
• Design and Pharmacological Activity of Phosphinic Acid Based NAALADase Inhibitors
  作者：Paul F. Jackson、Kevin L. Tays、Keith M. Maclin、Yao-Sen Ko、Weixing Li、Dil Vitharana、Takashi Tsukamoto、Doris Stoermer、Xi-Chun M. Lu、Krystyna Wozniak、Barbara S. Slusher

  DOI：10.1021/jm0001774

  日期：2001.11.1

  A novel series of phosphinic acid based inhibitors of the neuropeptidase NAALADase are described in this work. This series of compounds is the most potent series of inhibitors of the enzyme described to date. In addition, we have shown that these compounds are protective in animal models of neurodegeneration. Compound 34 significantly prevented neurodegeneration in a middle cerebral artery occlusion model of cerebral ischemia. In addition, in the chronic constrictive mc del of neuropathic pain, compound 34 significantly attenuated the hypersensitivity observed with saline-treated animals. These data suggest that NAALADase inhibition may provide a new approach for the treatment of both neurodegenerative disorders and peripheral neuropathies.