ethyl (8-fluoro-5-methyl-2,3-dioxo-1,4-dihydro-5H-indeno[1,2-b]pyrazin-5-yl)acetate | 286960-23-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl (8-fluoro-5-methyl-2,3-dioxo-1,4-dihydro-5H-indeno[1,2-b]pyrazin-5-yl)acetate
• 英文别名: Ethyl 2-(6-fluoro-9-methyl-2,3-dioxo-1,4-dihydroindeno[2,3-b]pyrazin-9-yl)acetate
• CAS: 286960-23-4
• 化学式: C₁₆H₁₅FN₂O₄
• 分子量: 318.305
• InChiKey: GOSZHUFLYFIAFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  84.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl (8-fluoro-5-methyl-2,3-dioxo-1,4-dihydro-5H-indeno[1,2-b]pyrazin-5-yl)acetate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 以76%的产率得到(6-Fluoro-9-methyl-2,3-dioxo-2,3,4,9-tetrahydro-1H-indeno[1,2-b]pyrazin-9-yl)-acetic acid
  参考文献：
  名称：

  Indeno[1,2-b]pyrazin-2,3-diones: A New Class of Antagonists at the Glycine Site of the NMDA Receptor with Potent in Vivo Activity

  摘要：

  Indeno[1,2-b]pyrazin-2,3-diones have been identified as a novel series of potent ligands on the glycine site of the NMDA receptor. To improve their in vivo activities, an acetic acid-type side chain was introduced to the 5-position, giving water-soluble compounds when formulated as the sodium salt (> 10 mg/mL). Introduction of a chlorine atom in the 8-position led to a dramatic improvement of anticonvulsant activity and this was surprising since this change did not improve binding affinity. A plausible explanation is a reduced recognition by a Na+,K+-ATPase active transport system responsible for the excretion of these compounds from the brain and kidney. This promising new chemical series led to the optically active isomer (-)-10i (RPR 118723), a glycine/NMDA antagonist with nanomolar binding affinity and in vivo activity in animal model of convulsions and electrophysiology at doses in the range of 2-3 mg/kg following iv administration.

  DOI：

  10.1021/jm990957g
• 作为产物：
  描述：

  ethyl (5-fluoro-1-methyl-3-oxo-1-indanyl)acetate 在 10percent Pd/C 盐酸 、 亚硝酸特丁酯 、 ammonium acetate 、 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 、 溶剂黄146 为溶剂， 20.0 ℃ 、180.0 kPa 条件下， 反应 25.0h， 生成 ethyl (8-fluoro-5-methyl-2,3-dioxo-1,4-dihydro-5H-indeno[1,2-b]pyrazin-5-yl)acetate
  参考文献：
  名称：

  Indeno[1,2-b]pyrazin-2,3-diones: A New Class of Antagonists at the Glycine Site of the NMDA Receptor with Potent in Vivo Activity

  摘要：

  Indeno[1,2-b]pyrazin-2,3-diones have been identified as a novel series of potent ligands on the glycine site of the NMDA receptor. To improve their in vivo activities, an acetic acid-type side chain was introduced to the 5-position, giving water-soluble compounds when formulated as the sodium salt (> 10 mg/mL). Introduction of a chlorine atom in the 8-position led to a dramatic improvement of anticonvulsant activity and this was surprising since this change did not improve binding affinity. A plausible explanation is a reduced recognition by a Na+,K+-ATPase active transport system responsible for the excretion of these compounds from the brain and kidney. This promising new chemical series led to the optically active isomer (-)-10i (RPR 118723), a glycine/NMDA antagonist with nanomolar binding affinity and in vivo activity in animal model of convulsions and electrophysiology at doses in the range of 2-3 mg/kg following iv administration.

  DOI：

  10.1021/jm990957g

文献信息

• Indeno[1,2-<i>b</i>]pyrazin-2,3-diones: A New Class of Antagonists at the Glycine Site of the NMDA Receptor with Potent in Vivo Activity
  作者：Patrick Jimonet、Yves Ribeill、Georg Andrees Bohme、Alain Boireau、Michel Chevé,、Dominique Damour、Adam Doble、Arielle Genevois-Borella、Frédéric Herman、Assunta Imperato、Sylvain Le Guern、Franco Manfré、Jeremy Pratt、John C. R. Randle、Jean-Marie Stutzmann、Serge Mignani

  DOI：10.1021/jm990957g

  日期：2000.6.1

  Indeno[1,2-b]pyrazin-2,3-diones have been identified as a novel series of potent ligands on the glycine site of the NMDA receptor. To improve their in vivo activities, an acetic acid-type side chain was introduced to the 5-position, giving water-soluble compounds when formulated as the sodium salt (> 10 mg/mL). Introduction of a chlorine atom in the 8-position led to a dramatic improvement of anticonvulsant activity and this was surprising since this change did not improve binding affinity. A plausible explanation is a reduced recognition by a Na+,K+-ATPase active transport system responsible for the excretion of these compounds from the brain and kidney. This promising new chemical series led to the optically active isomer (-)-10i (RPR 118723), a glycine/NMDA antagonist with nanomolar binding affinity and in vivo activity in animal model of convulsions and electrophysiology at doses in the range of 2-3 mg/kg following iv administration.