(5-chloro-1-methyl-3-oxo-1-indanyl)acetic acid | 173187-21-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (5-chloro-1-methyl-3-oxo-1-indanyl)acetic acid
• 英文别名: 2-(5-chloro-1-methyl-3-oxo-2H-inden-1-yl)acetic acid
• CAS: 173187-21-8
• 化学式: C₁₂H₁₁ClO₃
• 分子量: 238.671
• InChiKey: WXBSGQPQQRXVFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5-chloro-1-methyl-3-oxo-1-indanyl)acetic acid 在 10percent Pd/C 盐酸 、 亚硝酸特丁酯 、 草酰氯 、 ammonium acetate 、 氢气 、 溶剂黄146 、 三乙胺 、 N,N-二甲基甲酰胺 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 41.0h， 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 硫酸 、 sodium ethanolate 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 68.0h， 生成 (5-chloro-1-methyl-3-oxo-1-indanyl)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

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。
• DERIVES DE 5H-INDENO[1,2-b]PYRAZINE-2,3-DIONE ANTAGONISTES DES RECEPTEURS AMPA ET NMDA
  申请人：RHONE-POULENC RORER S.A.

  公开号：EP0752988B1

  公开（公告）日：1999-05-26
• DERIVES DE 5H-INDENO[1,2-b]PYRAZINE-2,3-DIONE, LEUR PREPARATION ET LES MEDICAMENTS LES CONTENANT
  申请人：RHONE-POULENC RORER S.A.

  公开号：EP0752988A1

  公开（公告）日：1997-01-15
• US5922716A
  申请人：——

  公开号：US5922716A

  公开（公告）日：1999-07-13
• [EN] 5H-INDENO[1,2-b]PYRAZINE-2,3-DIONE DERIVATIVES, PREPARATION THEREOF AND DRUGS CONTAINING SAME<br/>[FR] DERIVES DE 5H-INDENO[1,2-b]PYRAZINE-2,3-DIONE, LEUR PREPARATION ET LES MEDICAMENTS LES CONTENANT
  申请人：RHONE-POULENC RORER S.A.

  公开号：WO1995026342A1

  公开（公告）日：1995-10-05

  (EN) Compounds of formula (I), wherein R, R1, R2 and R3 are as defined in the description, salts thereof, the preparation thereof and drugs containing same, are disclosed. The compounds of formula (I) have valuable pharmacological properties and are alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic 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.(FR) Composés de formule (I) dans laquelle R, R1, R2 et R3 sont tels que définis dans la description, leurs sels, leur préparation et les médicaments les contenant. Les composés de formule (I) présentent des propriétés pharmacologiques intéressantes. Ces composés sont des antagonistes du récepteur de l'acide $g(a)-amino-3-hydroxy-5-méthyl-4-isoxazolepropionique (AMPA), connu aussi sous le nom de récepteur du quisqualate. Par ailleurs, les composés de formule (I) sont des antagonistes non compétitifs du récepteur N-méthyl-D-aspartate (NMDA) et, plus particulièrement, ce sont des ligands pour les sites modulateurs de la glycine du récepteur NMDA.