[5-(benzyloxy)-2-(benzyloxycarbonyl)-5-oxopentyl]phosphonic acid | 1001850-67-4

• 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: [5-(benzyloxy)-2-(benzyloxycarbonyl)-5-oxopentyl]phosphonic acid
• 英文别名: dibenzyl 2-phosphonomethyl-pentanedioate；(5-Oxo-5-phenylmethoxy-2-phenylmethoxycarbonylpentyl)phosphonic acid
• CAS: 1001850-67-4
• 化学式: C₂₀H₂₃O₇P
• 分子量: 406.372
• InChiKey: CJCNEEXULUGDEF-UHFFFAOYSA-N

物化性质

• 沸点：
  593.3±60.0 °C(Predicted)
• 密度：
  1.317±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  28
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [5-(benzyloxy)-2-(benzyloxycarbonyl)-5-oxopentyl]phosphonic acid 在 palladium 10% on activated carbon 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 20.0h， 生成 2-(膦酰甲基)戊烷二酸
  参考文献：
  名称：

  WO2008/8483

  摘要：

  公开号：
• 作为产物：
  描述：

  (5-(benzyloxy)-2-((benzyloxy)carbonyl)-5-oxopentyl)phosphinic acid 在 sodium periodate 作用下， 以 水 、 乙腈 为溶剂， 反应 3.0h， 生成 [5-(benzyloxy)-2-(benzyloxycarbonyl)-5-oxopentyl]phosphonic acid
  参考文献：
  名称：

  WO2008/8483

  摘要：

  公开号：

文献信息

• [EN] PRODRUGS OF PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA) INHIBITOR<br/>[FR] PROMÉDICAMENTS D'INHIBITEUR DE L'ANTIGÈNE MEMBRANAIRE SPÉCIFIQUE DE LA PROSTATE (PSMA)
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2016022827A1

  公开（公告）日：2016-02-11

  Methods and compounds are disclosed for treating a disease or condition by inhibiting PSMA (Prostate Specific Membrane Antigen) using prodrugs of 2-PMPA.

  揭示了一种通过使用2-PMPA的前药来抑制PSMA（前列腺特异性膜抗原）来治疗疾病或症状的方法和化合物。
• Prodrugs of prostate specific membrane antigen (PSMA) inhibitor
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US10544176B2

  公开（公告）日：2020-01-28

  Methods and compounds are disclosed for treating a disease or condition by inhibiting PSMA (Prostate Specific Membrane Antigen) using prodrugs of 2-PMPA.

  本研究公开了通过使用 2-PMPA 的原药抑制 PSMA（前列腺特异性膜抗原）来治疗疾病或病症的方法和化合物。
• Discovery of Orally Available Prodrugs of the Glutamate Carboxypeptidase II (GCPII) Inhibitor 2-Phosphonomethylpentanedioic Acid (2-PMPA)
  作者：Pavel Majer、Andrej Jančařík、Marcela Krečmerová、Tomáš Tichý、Lukáš Tenora、Krystyna Wozniak、Ying Wu、Elie Pommier、Dana Ferraris、Rana Rais、Barbara S. Slusher

  DOI：10.1021/acs.jmedchem.6b00062

  日期：2016.3.24

  2-Phosphonomethylpentanedioic acid (1, 2-PMPA) is a potent inhibitor of glutamate carboxypeptidase II which has demonstrated robust neuroprotective efficacy in many neurological disease models. However, 1 is highly polar containing a phosphonate and two carboxylates, severely limiting its oral bioavailability. We strategized to mask the polar groups via a prodrug approach, increasing the likelihood of passive oral absorption. Our initial strategy was to cover the phosphonate with hydrophobic moieties such as pivaloyloxymethyl (POM) and isopropyloxycarbonyloxymethyl (POC) while keeping the alpha- and gamma-carboxylates unsubstituted. This attempt was unsuccessful due to the chemical instability of the bis-POC/POM derivatives. Addition of alpha,gamma-diesters and alpha-monoesters enhanced chemical stability and provided excellent oral exposure in mice, but these mixed esters were too stable in vivo, resulting in minimal release of 1. By introducing POC groups on both the phosphonate and a-carboxylate, we synthesized Tris-POC-2-PMPA (21b), which afforded excellent release of 1 following oral administration in both mice and dog.
• PRODRUGS OF PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA) INHIBITOR
  申请人：The Johns Hopkins University

  公开号：EP3177632A1

  公开（公告）日：2017-06-14
• US9988407B2
  申请人：——

  公开号：US9988407B2

  公开（公告）日：2018-06-05