ethyl 2-cyano-3-(3,4-dichlorophenyl)-2-butenoate | 286959-64-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: ethyl 2-cyano-3-(3,4-dichlorophenyl)-2-butenoate
• 英文别名: 2-Cyano-3-(3,4-dichlorophenyl)-but-2-enoic acid ethyl ester；ethyl 2-cyano-3-(3,4-dichlorophenyl)but-2-enoate
• CAS: 286959-64-6
• 化学式: C₁₃H₁₁Cl₂NO₂
• 分子量: 284.142
• InChiKey: GGDQENOYWUIMBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 2-cyano-3-(3,4-dichlorophenyl)-2-butenoate 在 10percent Pd/C 盐酸 、 亚硝酸特丁酯 、 硫酸 、 氢气 、 sodium ethanolate 、 溶剂黄146 作用下， 以 乙醚 、 乙醇 、 溶剂黄146 为溶剂， 20.0 ℃ 、180.0 kPa 条件下， 反应 105.0h， 生成 ethyl (2-amino-5,6-dichloro-1-methyl-3-oxo-1-indanyl)acetate hydrochloride
  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：

  氰乙酸乙酯 、 3,4-二氯苯乙酮 在 ammonium acetate 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 以41%的产率得到ethyl 2-cyano-3-(3,4-dichlorophenyl)-2-butenoate
  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

• Pharmaceutically active compounds and methods of use
  申请人：Moorman R. Allan

  公开号：US20060183921A1

  公开（公告）日：2006-08-17

  New fused thiophene compounds are provided and methods of using those compounds for a variety of therapeutic indications. Compounds of the invention are particularly useful for treatment of neuropathic pain.

  提供了新的融合噻吩化合物，并且提供了使用这些化合物治疗各种疾病的方法。本发明的化合物特别适用于治疗神经病性疼痛。
• 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.