diethyl 2-acetamido-2-(3-iodobenzyl)malonate | 22753-30-6

• 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-(3-iodobenzyl)malonate
• 英文别名: Diethyl-m-iodbenzyl-acetamidomalonat
• CAS: 22753-30-6
• 化学式: C₁₆H₂₀INO₅
• 分子量: 433.243
• InChiKey: IZVPPOFCHGOENM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.83
• 重原子数：
  23.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  81.7
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  diethyl 2-acetamido-2-(3-iodobenzyl)malonate 、 3-氰基苯硼酸 在 bis-triphenylphosphine-palladium(II) chloride 、 三乙胺 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 0.25h， 以80%的产率得到diethyl 2-acetamido-2-((3'-cyanobiphenyl-3-yl)methyl)malonate
  参考文献：
  名称：

  3-Substituted phenylalanines as selective AMPA- and kainate receptor ligands

  摘要：

  On the basis of X-ray structures of ionotropic glutamate receptor constructs in complex with amino acid-based AMPA and kainate receptor antagonists, a series of rigid as well as flexible biaromatic alanine derivatives carrying selected hydrogen bond acceptors and donors have been synthesized in order to investigate the structural determinants for receptor selectivity between AMPA and the GluR5 subtype of kainate receptors. Compounds selective for either GluR5 or AMPA receptors were identified. One particular substituent position appeared to be of special importance for control of ligand selectivity. Using molecular modeling the observed structure-activity relationships at AMPA and GluR5 receptors were deduced. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.07.021
• 作为产物：
  描述：

  间碘甲苯 、 乙酰氨基丙二酸二乙酯 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 、 sodium hydride 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 生成 diethyl 2-acetamido-2-(3-iodobenzyl)malonate
  参考文献：
  名称：

  Studies on Aryl-Substituted Phenylalanines: Synthesis, Activity, and Different Binding Modes at AMPA Receptors

  摘要：

  A series of racemic aryl-substituted phenylalanines was synthesized and evaluated in vitro at recombinant rat GluA1-3, at GluK1-3, and at native AMPA receptors. The individual enantiomers of two target compounds, (RS)-2-amino-3-(3,4-dichloro-5-(5-hydroxypyridin-3-yl)phenyl)propanoic acid 37 and (RS)-2-amino-3-(3'-hydroxybiphenyl-3-yl)propanoic acid 38, were characterized. (S)-37 and (R)-38 were identified as the only biologically active isomers, both being antagonists at GluA2 receptors with K-b of 1.80 and 3.90 mu M, respectively. To address this difference in enantiopharmacology, not previously seen for amino acid-based AMPA receptor antagonists, X-ray crystal structures of both eutomers in complex with the GluA2 ligand binding domain were solved. The cocrystal structures of (S)-37 and (R)-38 showed similar interactions of the amino acid parts but unexpected and different orientations and interactions of the biaromatic parts of the ligands inside the binding site, with (R)-38 having a binding mode not previously identified for amino acid-based antagonists.

  DOI：

  10.1021/acs.jmedchem.5b01666