3-(1-methyl-2-nitro-2-tricyclo[3.3.1.1^3,7]decyl)propanoic acid

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 3-(1-methyl-2-nitro-2-tricyclo[3.3.1.1^3,7]decyl)propanoic acid
• 英文别名: 3-(1-Methyl-2-nitro-2-adamantyl)propanoic acid；3-(1-methyl-2-nitro-2-adamantyl)propanoic acid
• 化学式: C₁₄H₂₁NO₄
• 分子量: 267.325
• InChiKey: CLQXLELJXIOVLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(1-methyl-2-nitro-2-tricyclo[3.3.1.1^3,7]decyl)propanoic acid 在 盐酸 、 氢气 作用下， 以 乙醇 为溶剂， 80.0 ℃ 、344.75 kPa 条件下， 反应 24.0h， 生成 1-methyl-spiro[pyrrolidine-2,2'-adamantan]-5-one
  参考文献：
  名称：

  Binding and Proton Blockage by Amantadine Variants of the Influenza M2_WT and M2_S31N Explained

  摘要：

  While aminoadamantanes are well-established inhibitors of the influenza A M2 proton channel, the mechanisms by which they are rendered ineffective against M2(s31N) are unclear. Solid state NMR, isothermal titration calorimetry, electrophysiology, antiviral assays, and molecular dynamics simulations suggest stronger binding interactions for aminoadamantanes to M2(WT). compared to negligible or weak binding to M2s31N. This is due to reshaping of the M2 pore when N31 is present, which, in contrast to wild-type (WT), leads (A) to the loss of the V27 pocket for the adamantyl cage and to a predominant orientation of the ligand's ammonium group toward the N-terminus and (B) to the lack of a helical kink upon ligand binding. The kink, which reduces the tilt of the C-terminal helical domain relative to the bilayer normal, includes the W41 primary gate for proton conductance and may prevent the gate from opening, representing an alternative view for how these drugs prevent proton conductance.

  DOI：

  10.1021/acs.jmedchem.6b01115
• 作为产物：
  描述：

  1-methyl-2-adamantanone 在 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 盐酸羟胺 、 水 、 硝酸 、 苄基三甲基氢氧化铵 、 碳酸氢钠 、 sodium carbonate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 、 叔丁醇 为溶剂， 反应 16.17h， 生成 3-(1-methyl-2-nitro-2-tricyclo[3.3.1.1^3,7]decyl)propanoic acid
  参考文献：
  名称：

  Binding and Proton Blockage by Amantadine Variants of the Influenza M2_WT and M2_S31N Explained

  摘要：

  While aminoadamantanes are well-established inhibitors of the influenza A M2 proton channel, the mechanisms by which they are rendered ineffective against M2(s31N) are unclear. Solid state NMR, isothermal titration calorimetry, electrophysiology, antiviral assays, and molecular dynamics simulations suggest stronger binding interactions for aminoadamantanes to M2(WT). compared to negligible or weak binding to M2s31N. This is due to reshaping of the M2 pore when N31 is present, which, in contrast to wild-type (WT), leads (A) to the loss of the V27 pocket for the adamantyl cage and to a predominant orientation of the ligand's ammonium group toward the N-terminus and (B) to the lack of a helical kink upon ligand binding. The kink, which reduces the tilt of the C-terminal helical domain relative to the bilayer normal, includes the W41 primary gate for proton conductance and may prevent the gate from opening, representing an alternative view for how these drugs prevent proton conductance.

  DOI：

  10.1021/acs.jmedchem.6b01115

文献信息

• ANTIVIRAL COMPOUNDS
  申请人：BRIGHAM YOUNG UNIVERSITY

  公开号：US20150368196A1

  公开（公告）日：2015-12-24

  Compounds useful for treating and preventing viral infections including influenza are disclosed. Methods of treating or preventing viral infections, including influenza A infections are disclosed. Specifically, aminoadamantane derivatives that are structurally analogous to amantadine, including spirocyclic compounds, are provided for the treatment of amantadine-insensitive influenza infection in a subject.

  本文披露了用于治疗和预防包括流感在内的病毒感染的化合物。本文还披露了治疗或预防病毒感染，包括甲型流感感染的方法。具体而言，提供了与金刚烷胺结构类似的氨基金刚烷衍生物，包括螺环化合物，用于治疗对金刚烷胺不敏感的流感感染。
• US9840465B2
  申请人：——

  公开号：US9840465B2

  公开（公告）日：2017-12-12
• [EN] ANTIVIRAL COMPOUNDS<br/>[FR] COMPOSÉS ANTIVIRAUX
  申请人：UNIV BRIGHAM YOUNG

  公开号：WO2014121170A2

  公开（公告）日：2014-08-07

  Compounds useful for treating and preventing viral infections including influenza are disclosed. Methods of treating or preventing viral infections, including influenza A infections are disclosed.
• Binding and Proton Blockage by Amantadine Variants of the Influenza M2_WT and M2_S31N Explained
  作者：Christina Tzitzoglaki、Anna Wright、Kathrin Freudenberger、Anja Hoffmann、Ian Tietjen、Ioannis Stylianakis、Felix Kolarov、David Fedida、Michaela Schmidtke、Günter Gauglitz、Timothy A. Cross、Antonios Kolocouris

  DOI：10.1021/acs.jmedchem.6b01115

  日期：2017.3.9

  While aminoadamantanes are well-established inhibitors of the influenza A M2 proton channel, the mechanisms by which they are rendered ineffective against M2(s31N) are unclear. Solid state NMR, isothermal titration calorimetry, electrophysiology, antiviral assays, and molecular dynamics simulations suggest stronger binding interactions for aminoadamantanes to M2(WT). compared to negligible or weak binding to M2s31N. This is due to reshaping of the M2 pore when N31 is present, which, in contrast to wild-type (WT), leads (A) to the loss of the V27 pocket for the adamantyl cage and to a predominant orientation of the ligand's ammonium group toward the N-terminus and (B) to the lack of a helical kink upon ligand binding. The kink, which reduces the tilt of the C-terminal helical domain relative to the bilayer normal, includes the W41 primary gate for proton conductance and may prevent the gate from opening, representing an alternative view for how these drugs prevent proton conductance.