diethyl 2-acetamido-2-(5-chloro-2-(2-cyanoethyl)benzyl)malonate | 165115-22-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: diethyl 2-acetamido-2-(5-chloro-2-(2-cyanoethyl)benzyl)malonate
• 英文别名: Diethyl 2-acetamido-2-[[5-chloro-2-(2-cyanoethyl)phenyl]methyl]propanedioate
• CAS: 165115-22-0
• 化学式: C₁₉H₂₃ClN₂O₅
• 分子量: 394.855
• InChiKey: FKYSVCQSGSERMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  diethyl 2-acetamido-2-(5-chloro-2-(2-cyanoethyl)benzyl)malonate 在 硫酸 、 硝酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.5h， 以64%的产率得到diethyl 2-acetamido-2-(2-(3-amino-3-oxopropyl)-5-chloro-4-nitrobenzyl)malonate
  参考文献：
  名称：

  A New Phenylalanine Derivative Acts as an Antagonist at the AMPA Receptor GluA2 and Introduces Partial Domain Closure: Synthesis, Resolution, Pharmacology, and Crystal Structure

  摘要：

  In order to map out molecular determinants for competitive blockade of AMPA receptor subtypes, a series of 2-carboxyethylphenylalanine derivatives has been synthesized and pharmacologically characterized in vitro. One compound in this series, (RS)-3h, showed micromolar affinity for GluA1(o). and GluA2(R)(o) receptors with an approximately 4-fold preference for GluA1/2 vs GluA3/4. In TEVC electrophysiological experiments (RS)-3h competitively antagonized GluA2(Q)(i) receptors. The X-ray structure of the active enantiomer (S)-3h in complex with GluA2-S1S2J showed a domain closure around 8 degrees. Even though the nitro and the carboxyethyl groups of (S)-3h were both anchored to Tyr702 through a water H-bond network, these interactions only induced weak subtype selectivity. In spite of the fact that (S)-3h induced a domain closure close to that observed for partial agonists, it did not produce agonist responses at GluA2 receptors under nondesensitizing conditions. 2-Carboxyethylphenylalanine derivatives provide a new synthetic scaffold for the introduction of substituents that could lead to AMPA receptor subtype-selective ligands.

  DOI：

  10.1021/jm200862h
• 作为产物：
  描述：

  4-氯苯乙醇 在 氢溴酸 、 四氯化钛 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 41.5h， 生成 diethyl 2-acetamido-2-(5-chloro-2-(2-cyanoethyl)benzyl)malonate
  参考文献：
  名称：

  A New Phenylalanine Derivative Acts as an Antagonist at the AMPA Receptor GluA2 and Introduces Partial Domain Closure: Synthesis, Resolution, Pharmacology, and Crystal Structure

  摘要：

  In order to map out molecular determinants for competitive blockade of AMPA receptor subtypes, a series of 2-carboxyethylphenylalanine derivatives has been synthesized and pharmacologically characterized in vitro. One compound in this series, (RS)-3h, showed micromolar affinity for GluA1(o). and GluA2(R)(o) receptors with an approximately 4-fold preference for GluA1/2 vs GluA3/4. In TEVC electrophysiological experiments (RS)-3h competitively antagonized GluA2(Q)(i) receptors. The X-ray structure of the active enantiomer (S)-3h in complex with GluA2-S1S2J showed a domain closure around 8 degrees. Even though the nitro and the carboxyethyl groups of (S)-3h were both anchored to Tyr702 through a water H-bond network, these interactions only induced weak subtype selectivity. In spite of the fact that (S)-3h induced a domain closure close to that observed for partial agonists, it did not produce agonist responses at GluA2 receptors under nondesensitizing conditions. 2-Carboxyethylphenylalanine derivatives provide a new synthetic scaffold for the introduction of substituents that could lead to AMPA receptor subtype-selective ligands.

  DOI：

  10.1021/jm200862h

文献信息

• US5364876A
  申请人：——

  公开号：US5364876A

  公开（公告）日：1994-11-15
• A New Phenylalanine Derivative Acts as an Antagonist at the AMPA Receptor GluA2 and Introduces Partial Domain Closure: Synthesis, Resolution, Pharmacology, and Crystal Structure
  作者：Ewa Szymańska、Karla Frydenvang、Alberto Contreras-Sanz、Darryl S. Pickering、Elena Frola、Zorica Serafimoska、Birgitte Nielsen、Jette S. Kastrup、Tommy N. Johansen

  DOI：10.1021/jm200862h

  日期：2011.10.27

  In order to map out molecular determinants for competitive blockade of AMPA receptor subtypes, a series of 2-carboxyethylphenylalanine derivatives has been synthesized and pharmacologically characterized in vitro. One compound in this series, (RS)-3h, showed micromolar affinity for GluA1(o). and GluA2(R)(o) receptors with an approximately 4-fold preference for GluA1/2 vs GluA3/4. In TEVC electrophysiological experiments (RS)-3h competitively antagonized GluA2(Q)(i) receptors. The X-ray structure of the active enantiomer (S)-3h in complex with GluA2-S1S2J showed a domain closure around 8 degrees. Even though the nitro and the carboxyethyl groups of (S)-3h were both anchored to Tyr702 through a water H-bond network, these interactions only induced weak subtype selectivity. In spite of the fact that (S)-3h induced a domain closure close to that observed for partial agonists, it did not produce agonist responses at GluA2 receptors under nondesensitizing conditions. 2-Carboxyethylphenylalanine derivatives provide a new synthetic scaffold for the introduction of substituents that could lead to AMPA receptor subtype-selective ligands.