ethyl (5-chloro-1-methyl-3-oxo-1-indanyl)acetate | 173187-20-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: ethyl (5-chloro-1-methyl-3-oxo-1-indanyl)acetate
• 英文别名: ethyl 2-(5-chloro-1-methyl-3-oxo-2H-inden-1-yl)acetate
• CAS: 173187-20-7
• 化学式: C₁₄H₁₅ClO₃
• 分子量: 266.724
• InChiKey: OLPMXCMRYFTMDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (5-chloro-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-chloro-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
• 作为产物：
  描述：

  3-<4-Chlor-phenyl>-2-cyan-but-2-en-saeure-aethylester 在 草酰氯 、 硫酸 、 sodium ethanolate 、 溶剂黄146 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 84.0h， 生成 ethyl (5-chloro-1-methyl-3-oxo-1-indanyl)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

• 5H-indeno\x9b1,2-b!pyrazine-2,3-dione derivatives, their preparation and
  申请人：Rhone-Poulenc Rorer S.A.

  公开号：US05922716A1

  公开（公告）日：1999-07-13

  Compounds of formula (I): ##STR1## wherein R represents a CR.sub.4 R.sub.5, CHR.sub.6, or C.dbd.R.sub.7 radical and R.sub.3 represents an oxygen atom, salts thereof, the preparation thereof and drugs containing same. The compounds of formula (I) have valuable pharmacological properties and are alpha-amino-3-hydroxy-5-methyl-4-osoxaziepropionic acid (AMPA) receptor antagonists, said receptor also being known as the quisqualate receptor. Furthermore, the compounds of formula (I) are non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, and particularly NMDA receptor glycine modulation site ligands.

  式(I)化合物：##STR1##其中R表示CR₄R₅、CHR₆或C≡R₇基团，R₃表示氧原子，及其盐类，它们的制备方法以及含有这些化合物的药物。式(I)化合物具有宝贵的药理学特性，是α-氨基-3-羟基-5-甲基-4-异噁唑丙酸(AMPA)受体拮抗剂，该受体也称为quisqualate受体。此外，式(I)化合物是非竞争性N-甲基-D-天冬氨酸(NMDA)受体拮抗剂，特别是NMDA受体甘氨酸调节位点的配体。
• 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.