4-methylbenzyl-o-benzylphosphinic acid | 200698-32-4

• 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: 4-methylbenzyl-o-benzylphosphinic acid
• 英文别名: benzyl 4-methylbenzylphosphinate
• CAS: 200698-32-4
• 化学式: C₁₅H₁₇O₂P
• 分子量: 260.273
• InChiKey: OBQZPFKZSOYUNM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.19
• 重原子数：
  18.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  26.3
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  4-methylbenzyl-o-benzylphosphinic acid 在 5percent Pd/C 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 22.0h， 生成 2-[[(4-methylbenzyl)hydroxyphosphinyl]methyl]-pentanedioic 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：

  4-甲基苄溴 、 alkaline earth salt of/the/ methylsulfuric acid 在 ammonium phosphite 、 N,N'-二环己基碳二亚胺 、 六甲基二硅氮烷 作用下， 以 二氯甲烷 为溶剂， 反应 33.0h， 生成 4-methylbenzyl-o-benzylphosphinic 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

文献信息

• Chiral Guanidinium Salt Catalyzed Enantioselective Phospha-Mannich Reactions
  作者：Xiao Fu、Wei-Tian Loh、Yan Zhang、Tao Chen、Ting Ma、Hongjun Liu、Jianmin Wang、Choon-Hong Tan

  DOI：10.1002/anie.200903971

  日期：2009.9.21

  Zero, one, or two? Guanidinium catalyst 1⋅HBArF4 (ArF=3,5‐(CF3)2C6H3, Bn=benzyl, Ts=4‐toluenesulfonyl) was obtained in a single step from a commercially available diamine. By using this catalyst an asymmetric phospha‐Mannich reaction has been developed, involving secondary phosphine oxides and H‐phosphinates as the P nucleophile. A series of enantiomerically enriched α‐amino phosphine oxides (2), α‐amino

  零，一或两个？胍催化剂1⋅ HBAR ˚F 4（AR ˚F = 3,5-（CF 3）2 C ^ 6 ħ 3在从可商购的二胺单个步骤获得，BN =苄基，TS = 4甲苯磺酰基）。通过使用这种催化剂，已经开发了不对称的膦-曼尼希反应，涉及仲膦氧化物和H-次膦酸酯作为P亲核试剂。制备了一系列对映异构体富集的α-氨基膦氧化物（2），α-氨基次膦酸酯和H-次膦酸酯，它们含有一个P-手性中心。
• Certain dioic acid derivatives useful as NAALADase inhibitors
  申请人：Guilford Pharmaceuticals Inc.

  公开号：US06025344A1

  公开（公告）日：2000-02-15

  The present disclosure relates to dipeptidase inhibitors, and more particularly, to novel phosphonate derivatives, hydroxyphosphinyl derivatives, and phosphoramidate derivatives that inhibit N-Acetylated .alpha.-Linked Acidic Dipeptidase (NAALADase) enzyme activity, pharmaceutical compositions comprising such derivatives, and methods of using such derivatives to inhibit NAALADase activity, and to treat prostate diseases, especially using the compounds of the present invention for the inhibition of the growth of prostate cancer cells.

  本公开涉及二肽酶抑制剂，更具体地说，涉及抑制N-乙酰化α-连接酸性二肽酶（NAALADase）酶活性的新磷酸酯衍生物、羟基磷酰衍生物和磷酰胺衍生物，包括这些衍生物的药物组合物，以及使用这些衍生物抑制NAALADase活性并治疗前列腺疾病的方法，尤其是使用本发明的化合物来抑制前列腺癌细胞的生长。
• Inhibitors of NAALADase enzyme activity
  申请人：Guilford Pharmaceuticals Inc.

  公开号：US06025345A1

  公开（公告）日：2000-02-15

  The present disclosure relates to dipeptidase inhibitors, and more particularly, to novel methods of using phosphonate derivatives, hydroxyphosphinyl derivatives, and phosphoramidate derivatives to inhibit N-Acetylated .alpha.-Linked Acidic Dipeptidase (NAALADase) enzyme activity, and to treat prostate diseases, especially using the compounds of the present invention for the inhibition of the growth of prostate cancer cells.

  本公开涉及二肽酶抑制剂，更特别地，涉及使用磷酸酯衍生物、羟基磷酰衍生物和磷酰胺衍生物的新方法来抑制N-乙酰化.α.-连接的酸性二肽酶（NAALADase）酶活性，并治疗前列腺疾病，特别是使用本发明的化合物抑制前列腺癌细胞生长。
• NAALADase inhibitors
  申请人：Guilford Pharmaceuticals Inc.

  公开号：US06046180A1

  公开（公告）日：2000-04-04

  The present disclosure relates to dipeptidase inhibitors, and more particularly, to novel phosphonate derivatives, hydroxyphosphinyl derivatives, and phosphoramidate derivatives that inhibit N-Acetylated .alpha.-Linked Acidic Dipeptidase (NAALADase) enzyme activity, pharmaceutical compositions comprising such derivatives, and methods of using such derivatives to inhibit NAALADase activity, and to treat prostate diseases, especially using the compounds of the present invention for the inhibition of the growth of prostate cancer cells.

  本公开涉及二肽酶抑制剂，更特别地，涉及抑制N-乙酰化α-连接酸性二肽酶（NAALADase）酶活性的新磷酸酯衍生物、羟基磷酰衍生物和磷酰胺衍生物，包括这些衍生物的药物组合物，以及使用这些衍生物抑制NAALADase活性和治疗前列腺疾病的方法，尤其是利用本发明化合物抑制前列腺癌细胞生长。
• 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。