diethyl 2-acetamido-2-(2-(3-amino-3-oxopropyl)-5-chloro-4-cyanobenzyl)malonate | 1337915-63-5

• 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-(2-(3-amino-3-oxopropyl)-5-chloro-4-cyanobenzyl)malonate
• 英文别名: Diethyl 2-acetamido-2-[[2-(3-amino-3-oxopropyl)-5-chloro-4-cyanophenyl]methyl]propanedioate
• CAS: 1337915-63-5
• 化学式: C₂₀H₂₄ClN₃O₆
• 分子量: 437.88
• InChiKey: BNPQZHZCMGNWKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  30
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  149
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl 2-acetamido-2-(2-(3-amino-3-oxopropyl)-5-chloro-4-cyanobenzyl)malonate 在 氢溴酸 作用下， 以 水 为溶剂， 反应 2.0h， 以35%的产率得到(RS)-4-(2-amino-2-carboxyethyl)-5-(2-carboxyethyl)-2-chlorobenzoic acid
  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 盐酸 、 硫酸 、 水 、 氢溴酸 、 硝酸 、 四氯化钛 、 铁粉 、 sodium hydride 、 N,N-二异丙基乙胺 、 sodium nitrite 作用下， 以 乙醇 、 二氯甲烷 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 49.75h， 生成 diethyl 2-acetamido-2-(2-(3-amino-3-oxopropyl)-5-chloro-4-cyanobenzyl)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