3-{2-[8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethyl}-1,5-dimethyl-3-oxido-7-oxo-7-phenyl-2,4,6-trioxa-3-phosphahept-1-yl benzoate

• 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: 3-{2-[8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethyl}-1,5-dimethyl-3-oxido-7-oxo-7-phenyl-2,4,6-trioxa-3-phosphahept-1-yl benzoate
• 英文别名: {2-[8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethyl}phosphonic acid bis[1-(benzyloxy)ethyl] ester；[2-[8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1 (7)-en-2-yl]ethyl]-phosphonic acid bis[1-(benzoyloxy)ethyl]ester；1-[1-benzoyloxyethoxy-[2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]phosphoryl]oxyethyl benzoate
• 化学式: C₂₇H₂₉N₂O₉P
• 分子量: 556.509
• InChiKey: QDTOKEYAZZSRBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  39
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  3-{2-[8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethyl}-1,5-dimethyl-3-oxido-7-oxo-7-phenyl-2,4,6-trioxa-3-phosphahept-1-yl benzoate 反应 7.0h， 生成
  参考文献：
  名称：

  Prodrugs of Perzinfotel with Improved Oral Bioavailability

  摘要：

  Previous studies with perzinfotel (1), a potent, selective, competitive NMDA receptor antagonist, showed it to be efficacious in inflammatory and neuropathic pain models. To increase the low oral bioavailability of 1 (3-5%), prodrug derivatives (3a-h) were synthesized and evaluated. The oxymethylene-spaced diphenyl analogue 3a demonstrated good stability at acidic and neutral pH, as well as in simulated gastric fluid. In rat plasma, 3a was rapidly converted to 1 via 2a. Pharmacokinetic Studies indicated that the amount of systemic exposure of 1 produced by a 10 mg/kg oral dose of 3a was 2.5-fold greater than that produced by. a 30 mg/kg oral dose of L Consistent with these results, 3a was significantly more potent and had a longer duration of activity than I following oral administration in a rodent model of inflammatory pain. Taken together, these results demonstrate that an oxymethylene-spaced prodrug approach increased the bioavailability of 1.

  DOI：

  10.1021/jm8011799
• 作为产物：
  描述：

  苯甲酸 1-氯乙基酯 、 [2-(8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]-phosphonic Acid 在 N,N-二异丙基乙胺 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 36.5h， 生成 3-{2-[8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethyl}-1,5-dimethyl-3-oxido-7-oxo-7-phenyl-2,4,6-trioxa-3-phosphahept-1-yl benzoate
  参考文献：
  名称：

  [EN] DERIVATIVES OF 2-(8,9-DIOXO-2,6-DIAZABICYCLO(5.2.0)NON-1(7)-EN-2-YL)ALKYL PHOSPHONIC ACID AND THEIR USE AS N-METHYL-D-ASPARTATE (NMDA) RECETOR ANTAGONISTS
  [FR] DERIVES D'ACIDE 2-(8,9-DIOXO-2,6-DIAZABICYCLO(5.2.0)NON-1(7)-EN-2-YL)ALKYL PHOSPHONIQUE ET LEUR UTILISATION COMME ANTAGONISTES DU RECEPTEUR N-METHYL-D-ASPARTATE (NMDA)

  摘要：

  提供了式（I）的化合物或其药用可接受的盐，其中R2或R3中至少有一个不是氢。本发明的化合物是N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，对治疗受益于抑制NMDA受体的哺乳动物中存在的各种疾病是有用的。

  公开号：

  WO2004092189A1
• 作为试剂：
  描述：

  [2-(8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]-phosphonic Acid 、 N,N-二异丙基乙胺 、 苯甲酸 1-氯乙基酯 在 乙酸乙酯 、 碳酸氢钠 、 Brine 、 magnesium sulfate 、 silica gel 、 甲醇 、 氯仿 、 3-{2-[8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethyl}-1,5-dimethyl-3-oxido-7-oxo-7-phenyl-2,4,6-trioxa-3-phosphahept-1-yl benzoate 作用下， 以 N,N-二甲基甲酰胺 、 柠檬酸 为溶剂， 反应 36.5h， 以afforded 1.66 g (15.5%) of a stereoisomer of [2-[8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethyl]-phosphonic acid bis[1-(benzoyloxy)ethyl]ester (example 8) [MS (ES+): m/e 557 (M+H)] and 0.73 g (6.8%) of a less polar diastereoisomer of [2-[8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethyl]-phosphonic acid bis[1-(benzoyloxy)ethyl]ester (example 9) [MS (ES+): m/e 557 (M+H)]的产率得到3-{2-[8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethyl}-1,5-dimethyl-3-oxido-7-oxo-7-phenyl-2,4,6-trioxa-3-phosphahept-1-yl benzoate
  参考文献：
  名称：

  Derivatives of [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)alkyl] phosphonic acid and methods of use thereof

  摘要：

  本发明提供化学式(I)的化合物或其药学上可接受的盐，其中R2或R3中至少有一个不是氢。本发明的化合物是N-甲基-D-天门冬氨酸（NMDA）受体拮抗剂，可用于治疗哺乳动物中存在的多种病症，这些病症受到抑制NMDA受体的益处。

  公开号：

  US20050004080A1

文献信息

• Derivatives of [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)alkyl] Phosphonic Acid and Methods of Use Thereof
  申请人：Baudy B. Reinhardt

  公开号：US20070225257A1

  公开（公告）日：2007-09-27

  Compounds of formula (I) or pharmaceutically acceptable salts thereof are provided where at least one of R 2 or R 3 is not hydrogen. The compounds of the present invention are N-methyl-D-aspartate (NMDA) receptor antagonists and are useful in treating a variety of conditions present in a mammal that benefit from inhibiting the NMDA receptor.

  提供式(I)的化合物或其药学上可接受的盐，其中至少有一个R2或R3不是氢。本发明的化合物是N-甲基-D-天门冬氨酸（NMDA）受体拮抗剂，可用于治疗哺乳动物中存在的多种需要抑制NMDA受体的疾病。
• DERIVATIVES OF 2-(8,9-DIOXO-2,6-DIAZABICYCLO(5.2.0)NON-1(7)-EN-2-YL)ALKYL PHOSPHONIC ACID AND THEIR USE AS N-METHYL-D-ASPARTATE (NMDA) RECETOR ANTAGONISTS
  申请人：Wyeth LLC

  公开号：EP1611144B1

  公开（公告）日：2010-09-15
• EP1622625A1
  申请人：——

  公开号：EP1622625A1

  公开（公告）日：2006-02-08
• US7253153B2
  申请人：——

  公开号：US7253153B2

  公开（公告）日：2007-08-07
• US7879825B2
  申请人：——

  公开号：US7879825B2

  公开（公告）日：2011-02-01