N-(pyridin-4-ylmethylene)-1-(piperidin-4-yl)methanamine | 1403469-92-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-(pyridin-4-ylmethylene)-1-(piperidin-4-yl)methanamine
• CAS: 1403469-92-0
• 化学式: C₁₂H₁₇N₃
• 分子量: 203.287
• InChiKey: CFHNNQBHLAINSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  37.28
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  N-(pyridin-4-ylmethylene)-1-(piperidin-4-yl)methanamine 在 sodium tetrahydroborate 、 三乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 34.0h， 生成 (4-((methyl(pyridin-4-ylmethyl)amino)methyl)piperidin-1-yl)(phenyl)methanone
  参考文献：
  名称：

  Another Brick in the Wall. Validation of the σ₁ Receptor 3D Model by Computer-Assisted Design, Synthesis, and Activity of New σ₁ Ligands

  摘要：

  Originally considered an enigmatic polypeptide, the sigma(1) receptor has recently been identified as a unique ligand-regulated protein. Many studies have shown the potential of sigma(1) receptor ligands for the treatment of various diseases of the central nervous system (CNS); nevertheless, almost no information about the 3D structure of the receptor and/or the possible modes of interaction of the sigma(1) protein with its ligands have been unveiled so far. With the present work we validated our sigma(1) 3D homology model and assessed its reliability as a platform for sigma(1) ligand structure-based drug design. To this purpose, the 3D sigma(1) model was exploited in the design of 33 new sigma(1) ligands and in their ranking for receptor affinity by extensive molecular dynamics simulation-based free energy calculations. Also, the main interactions involved in receptor/ligand binding were analyzed by applying a per residue free energy deconvolution and in silico alanine scanning mutagenesis calculations. Subsequently, all compounds were synthesized M our laboratory and tested for sigma(1) binding activity in vitro. The agreement between in silk and in vitro results confirms the reliability of the proposed sigma(1) 3D model in the a priori prediction of the affinity of new sigma(1) ligands. Moreover, it also supports and corroborates the currently available biochemical data concerning the sigma(1) protein residues considered essential for sigma(1) ligand binding and activity.

  DOI：

  10.1021/mp300233y
• 作为产物：
  描述：

  4-吡啶甲醛 、 4-氨甲基哌啶 在 sodium sulfate 作用下， 以 氯仿 为溶剂， 反应 24.0h， 生成 N-(pyridin-4-ylmethylene)-1-(piperidin-4-yl)methanamine
  参考文献：
  名称：

  Another Brick in the Wall. Validation of the σ₁ Receptor 3D Model by Computer-Assisted Design, Synthesis, and Activity of New σ₁ Ligands

  摘要：

  Originally considered an enigmatic polypeptide, the sigma(1) receptor has recently been identified as a unique ligand-regulated protein. Many studies have shown the potential of sigma(1) receptor ligands for the treatment of various diseases of the central nervous system (CNS); nevertheless, almost no information about the 3D structure of the receptor and/or the possible modes of interaction of the sigma(1) protein with its ligands have been unveiled so far. With the present work we validated our sigma(1) 3D homology model and assessed its reliability as a platform for sigma(1) ligand structure-based drug design. To this purpose, the 3D sigma(1) model was exploited in the design of 33 new sigma(1) ligands and in their ranking for receptor affinity by extensive molecular dynamics simulation-based free energy calculations. Also, the main interactions involved in receptor/ligand binding were analyzed by applying a per residue free energy deconvolution and in silico alanine scanning mutagenesis calculations. Subsequently, all compounds were synthesized M our laboratory and tested for sigma(1) binding activity in vitro. The agreement between in silk and in vitro results confirms the reliability of the proposed sigma(1) 3D model in the a priori prediction of the affinity of new sigma(1) ligands. Moreover, it also supports and corroborates the currently available biochemical data concerning the sigma(1) protein residues considered essential for sigma(1) ligand binding and activity.

  DOI：

  10.1021/mp300233y