Diethyl 9-ethoxycarbonylmethyl-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-phosphonate | 183735-80-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并[1，2-a]吡嗪-8-酮
• 英文名称: Diethyl 9-ethoxycarbonylmethyl-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-phosphonate
• 英文别名: Ethyl 2-(4-diethoxyphosphoryl-7-oxo-2,5,8-triazatetracyclo[7.7.0.02,6.010,15]hexadeca-1(9),3,5,10,12,14-hexaen-14-yl)acetate
• CAS: 183735-80-0
• 化学式: C₂₁H₂₄N₃O₆P
• 分子量: 445.412
• InChiKey: AXZURZGQGAOKRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Diethyl 9-ethoxycarbonylmethyl-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-phosphonate 在 盐酸 作用下， 以79%的产率得到RPR 119990
  参考文献：
  名称：

  Canton, Thierry; Boehme, Georg Andrees; Boireau, Alain, Journal of Pharmacology and Experimental Therapeutics, 2001, vol. 299, # 1, p. 314 - 322

  摘要：

  DOI：
• 作为产物：
  描述：

  乙基磷酸二乙酯 在 ammonium acetate 、 potassium carbonate 、 溶剂黄146 作用下， 以 丙酮 为溶剂， 生成 Diethyl 9-ethoxycarbonylmethyl-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-phosphonate
  参考文献：
  名称：

  Bioisosteres of 9-Carboxymethyl-4-oxo-imidazo[1,2- a ]indeno[1,2- e ]pyrazin-2-carboxylic acid derivatives. Progress towards selective, potent In Vivo AMPA antagonists with longer durations of action

  摘要：

  A novel series of 2- and 9-disubstituted heterocyclic-fused 4-oxo-indeno[1,2-e]pyrazin derivatives was synthesized. One of them, the 9-(1 H-tetrazol-5-ylmethyl)-4-oxo-5,10-dihydroimidazo[1,2-a]indeno[1,2-e]pyrazin-2-yl phosphonic acid 4i exhibited a strong and a selective binding affinity for the AMPA receptor (IC50 = 13 nM) and demonstrated potent antagonist activity (IC50 = 6 nM) at the ionotropic AMPA receptor. This compound also displayed good anticonvulsant properties against electrically-induced convulsions after ip and iv administration with ED50 values between 0.8 and 1 mg/kg. Furthermore, a strong increase in potency was observed when given iv 3 h before test (ED50 = 3.5 instead of 25.6 mg/kg for the corresponding 9-carboxymethyl-2-carboxylic acid analogue). These data confirmed that there is an advantage in replacing the classical carboxy substituents by their bioisosteres such as tetrazole or phosphonic acid groups. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00592-8

文献信息

• 5H,10H-imidazo\x9b1,2-a!indeno\x9b1,2-e!pyrazin-4-one derivatives, preparation
  申请人：Rhone-Poulenc Rorer S.A.

  公开号：US05902803A1

  公开（公告）日：1999-05-11

  Compounds of formula (I), wherein R is a hydrogen atom or a carboxy, alkoxycarbonyl, --CO--NR.sub.4 R.sub.5, --PO.sub.3 H.sub.2 or --CH.sub.2 OH radical, and R.sub.1 is an -alk-NH.sub.2, -alk-NH--CO--R.sub.3, -alk-COOR.sub.4, -alk-CO--NR.sub.5 R.sub.6 or --CO--NH--R.sub.7 radical. The compounds of formula (I) have valuable pharmacological properties and are antagonists of the .alpha.-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor also known as the quisqualate receptor. Furthermore, the compounds of formula (I) are non-competitive antagonists of the N-methyl-D-aspartame (NMDA) receptor and more specifically are ligands for NMDA receptor glycine modulator sites.

  式(I)化合物，其中R为氢原子或羧基、烷氧羰基、--CO--NR₄R₅、--PO₃H₂或--CH₂OH基团，R₁为-烷基-NH₂、-烷基-NH--CO--R₃、-烷基-COOR₄、-烷基-CO--NR₅R₆或--CO--NH--R₇基团。式(I)化合物具有宝贵的药理特性，是α-氨基-3-羟基-5-甲基-4-异噁唑丙酸(AMPA)受体即quisqualate受体的拮抗剂。此外，式(I)化合物是非竞争性N-甲基-D-天冬氨酸(NMDA)受体的拮抗剂，更具体地说是NMDA受体甘氨酸调节位点的配体。
• US6057454A
  申请人：——

  公开号：US6057454A

  公开（公告）日：2000-05-02
• Bioisosteres of 9-Carboxymethyl-4-oxo-imidazo[1,2- a ]indeno[1,2- e ]pyrazin-2-carboxylic acid derivatives. Progress towards selective, potent In Vivo AMPA antagonists with longer durations of action
  作者：Patrick Jimonet、Georg Andrees Bohme、Jean Bouquerel、Alain Boireau、Dominique Damour、Marc Williams Debono、Arielle Genevois-Borella、Jean-Claude Hardy、Philippe Hubert、Franco Manfré、Patrick Nemecek、Jeremy Pratt、John C.R. Randle、Yves Ribeill、Jean-Marie Stutzmann、Marc Vuilhorgne、Serge Mignani

  DOI：10.1016/s0960-894x(00)00592-8

  日期：2001.1

  A novel series of 2- and 9-disubstituted heterocyclic-fused 4-oxo-indeno[1,2-e]pyrazin derivatives was synthesized. One of them, the 9-(1 H-tetrazol-5-ylmethyl)-4-oxo-5,10-dihydroimidazo[1,2-a]indeno[1,2-e]pyrazin-2-yl phosphonic acid 4i exhibited a strong and a selective binding affinity for the AMPA receptor (IC50 = 13 nM) and demonstrated potent antagonist activity (IC50 = 6 nM) at the ionotropic AMPA receptor. This compound also displayed good anticonvulsant properties against electrically-induced convulsions after ip and iv administration with ED50 values between 0.8 and 1 mg/kg. Furthermore, a strong increase in potency was observed when given iv 3 h before test (ED50 = 3.5 instead of 25.6 mg/kg for the corresponding 9-carboxymethyl-2-carboxylic acid analogue). These data confirmed that there is an advantage in replacing the classical carboxy substituents by their bioisosteres such as tetrazole or phosphonic acid groups. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Canton, Thierry; Boehme, Georg Andrees; Boireau, Alain, Journal of Pharmacology and Experimental Therapeutics, 2001, vol. 299, # 1, p. 314 - 322
  作者：Canton, Thierry、Boehme, Georg Andrees、Boireau, Alain、Bordier, Francoise、Mignani, Serge、Jimonet, Patrick、Jahn, Ghafoor、Alavijeh, Mohammad、Stygall, James、Roberts, Simon、Brealey, Clive、Vuilhorgne, Marc、Debono, Marc-William、Le Guern, Sylvain、Laville, Michel、Briet, Dominique、Roux, Michel、Stutzmann, Jean-Marie、Pratt, Jeremy

  DOI：——

  日期：——