N-(2-bromoethyl)-3,3-dimethylglutarimide | 101079-07-6

• 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: N-(2-bromoethyl)-3,3-dimethylglutarimide
• 英文别名: 1-(2-Bromoethyl)-4,4-dimethyl-piperidinyl-2,6-dione；1-(2-Bromoethyl)-4,4-dimethylpiperidine-2,6-dione
• CAS: 101079-07-6
• 化学式: C₉H₁₄BrNO₂
• 分子量: 248.12
• InChiKey: AOYJXSZTKOSLBB-UHFFFAOYSA-N

物化性质

• 沸点：
  334.0±25.0 °C(Predicted)
• 密度：
  1.380±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(2-氯苯基)哌嗪 、 N-(2-bromoethyl)-3,3-dimethylglutarimide 在 三乙胺 作用下， 反应 0.5h， 生成 1-{2-[4-(2-Chloro-phenyl)-piperazin-1-yl]-ethyl}-4,4-dimethyl-piperidine-2,6-dione
  参考文献：
  名称：

  Synthesis, Screening, and Molecular Modeling of New Potent and Selective Antagonists at the α_1d Adrenergic Receptor

  摘要：

  In the present study, more than 75 compounds structurally related to BMY 7378 have been designed and synthesized. Structural variations of each part of the reference molecule have been introduced, obtaining highly selective ligands for the aid adrenergic receptor. The molecular determinants for selectivity at this receptor are essentially, held by the phenyl substituent in the phenylpiperazine moiety. The integration of an extensive SAR analysis with docking simulations using the rhodopsin-based models of the three alpha(1)-AR subtypes and of the 5-HT1A receptor provides significant insights into the characterization of the receptor binding sites as well as into the molecular determinants of ligand selectivity at the alpha(1d)-AR and the 5-HT1A receptors. The results of multiple copies simultaneous search (MCSS) on the substituted phenylpiperazines together with those of manual docking of compounds BAN 7378 and 69 into the putative binding sites of the alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR, and the 5-HT1A receptors suggest that the phenylpiperazine moiety would dock into a site formed by amino acids in helices 3, 4, 5, 6 and extracellular loop 2, (E2), whereas the spirocyclic ring of the ligand docks into a site formed by amino acids of helices 1, 2, 3, and 7. This docking mode is consistent with the SAR data produced in this work. Furthermore, the binding site of the imide moiety does not allow for the simultaneous involvement of the two carbonyl oxygen atoms in H-bonding, interactions, consistent with the SAR data, in particular with the results obtained with the lactam derivative 128. The results of docking simulations also suggest that the second and third extracellular loops may act as selectivity filters for the substituted phenylpiperazines. The most potent and selective compounds for alpha(1d) adrenergic receptor, i.e., 69 (Rec 26D/038) and 128 (Rec 26D/073), are characterized by the presence of the 2,5-dichlorophenylpiperazine moiety.

  DOI：

  10.1021/jm030944+
• 作为产物：
  描述：

  N-bromo-3,3-dimethylglutarimide 、 乙烯 在 TBPD 作用下， 以 氘代氯仿 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 N-(2-bromoethyl)-3,3-dimethylglutarimide
  参考文献：
  名称：

  Free radical addition of N-bromoglutarimides and N-bromophthalimide to alkenes. Absolute and relative rates

  摘要：

  DOI：

  10.1021/jo00361a027

文献信息

• Synthèse de N-(2-Hydroxyéthyl)iminoglutarimides à partir de N-(2-Bromoéthyl)glutarimides
  作者：Tchao Podona、Saïd Lazar、Gérard Coudert、Gérald Guillaumet

  DOI：10.1016/s0040-4020(01)81290-4

  日期：1993.5

  The reaction of primary amines with N-(2-bromoethyl)glutarimide derivatives leads to N-(2-hydroxy-ethyl)iminoglutarimides in good yields. The possible mechanism is proposed.
• Synthesis, Screening, and Molecular Modeling of New Potent and Selective Antagonists at the α_1d Adrenergic Receptor
  作者：Amedeo Leonardi、Daniela Barlocco、Federica Montesano、Giorgio Cignarella、Gianni Motta、Rodolfo Testa、Elena Poggesi、Michele Seeber、Pier G. De Benedetti、Francesca Fanelli

  DOI：10.1021/jm030944+

  日期：2004.4.1

  In the present study, more than 75 compounds structurally related to BMY 7378 have been designed and synthesized. Structural variations of each part of the reference molecule have been introduced, obtaining highly selective ligands for the aid adrenergic receptor. The molecular determinants for selectivity at this receptor are essentially, held by the phenyl substituent in the phenylpiperazine moiety. The integration of an extensive SAR analysis with docking simulations using the rhodopsin-based models of the three alpha(1)-AR subtypes and of the 5-HT1A receptor provides significant insights into the characterization of the receptor binding sites as well as into the molecular determinants of ligand selectivity at the alpha(1d)-AR and the 5-HT1A receptors. The results of multiple copies simultaneous search (MCSS) on the substituted phenylpiperazines together with those of manual docking of compounds BAN 7378 and 69 into the putative binding sites of the alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR, and the 5-HT1A receptors suggest that the phenylpiperazine moiety would dock into a site formed by amino acids in helices 3, 4, 5, 6 and extracellular loop 2, (E2), whereas the spirocyclic ring of the ligand docks into a site formed by amino acids of helices 1, 2, 3, and 7. This docking mode is consistent with the SAR data produced in this work. Furthermore, the binding site of the imide moiety does not allow for the simultaneous involvement of the two carbonyl oxygen atoms in H-bonding, interactions, consistent with the SAR data, in particular with the results obtained with the lactam derivative 128. The results of docking simulations also suggest that the second and third extracellular loops may act as selectivity filters for the substituted phenylpiperazines. The most potent and selective compounds for alpha(1d) adrenergic receptor, i.e., 69 (Rec 26D/038) and 128 (Rec 26D/073), are characterized by the presence of the 2,5-dichlorophenylpiperazine moiety.
• Free radical addition of N-bromoglutarimides and N-bromophthalimide to alkenes. Absolute and relative rates
  作者：Ulrich Luning、Douglas S. McBain、Philip S. Skell

  DOI：10.1021/jo00361a027

  日期：1986.5