2,4-dicyano-3-methyl-3-(4-chlorophenyl)glutarimide | 92161-82-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2,4-dicyano-3-methyl-3-(4-chlorophenyl)glutarimide
• 英文别名: 2,4-dicyano-3-methyl-3-(p-chlorophenyl)glutarimide；4-(4-chloro-phenyl)-4-methyl-2,6-dioxo-piperidine-3,5-dicarbonitrile；4-<4-Chlor-phenyl>-4-methyl-3,5-dicyan-glutarsaeureimid；4-(4-Chlorophenyl)-4-methyl-2,6-dioxopiperidine-3,5-dicarbonitrile
• CAS: 92161-82-5
• 化学式: C₁₄H₁₀ClN₃O₂
• mdl: MFCD28118401
• 分子量: 287.705
• InChiKey: FQOYMSDHFWUJMM-UHFFFAOYSA-N

物化性质

• 熔点：
  261 °C
• 沸点：
  583.8±50.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.285
• 拓扑面积：
  93.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,4-dicyano-3-methyl-3-(4-chlorophenyl)glutarimide 在 10percent Pd/C 盐酸 、 亚硝酸特丁酯 、 草酰氯 、 硫酸 、 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 105.0h， 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：

  对氯苯乙酮 在 ammonium acetate 、 sodium ethanolate 、 溶剂黄146 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 4.0h， 生成 2,4-dicyano-3-methyl-3-(4-chlorophenyl)glutarimide
  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

• Structures and fluorescence of secondary products produced from the cope-knoevenagel reaction of 2-phenylpropionaldehyde with methyl cyanoacetate
  作者：Wakatu Nagai、Yumiko Hirata、Masao Kawai、Kiyoaki Tanaka

  DOI：10.1002/jhet.5570330122

  日期：1996.1

  of 2-phenylpropionaldehyde (7) with methyl cyanoacetate (8) produced methyl (E)-2-cyano-4-phenylpent-2-enoate (9) and the two highly fluorescent secondary products, 2-amino-3-carbomethoxy-6-phenyl-4-(1-phenylethyl)pyridine (10) and 3-cyano-6-phenyl-4-(1-phenylethyl)-2-pyridone (11). The structure of 10 was determined by X-ray crystallography while the structure of 11 was confirmed by the conversion

  2-苯基丙醛（7）与氰基乙酸甲酯（8）的Cope-Knoevenagel反应产生了（E）-2-氰基-4-苯基戊-2-烯酸甲酯（9）和两种高荧光副产物2-氨基- 3-碳甲氧基-6-苯基-4-（1-苯乙基）吡啶（10）和3-氰基-6-苯基-4-（1-苯乙基）-2-吡啶酮（11）。通过X射线晶体学确定10的结构，同时通过将9转化为11来确认11的结构。讨论了它们的形成机理。10和11的荧光 还描述了相关化合物。
• 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.