(4-(((4-chlorobenzyl)(methyl)amino)methyl)piperidin-1-yl)(phenyl)methanone | 1331746-50-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4-(((4-chlorobenzyl)(methyl)amino)methyl)piperidin-1-yl)(phenyl)methanone
• 英文别名: [4-[[(4-Chlorophenyl)methyl-methylamino]methyl]piperidin-1-yl]-phenylmethanone
• CAS: 1331746-50-9
• 化学式: C₂₁H₂₅ClN₂O
• 分子量: 356.895
• InChiKey: JGUHHLBDCRMNGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-氨甲基哌啶 在 sodium tetrahydroborate 、 sodium sulfate 、 三乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 氯仿 为溶剂， 反应 58.0h， 生成 (4-(((4-chlorobenzyl)(methyl)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

文献信息

• Another Brick in the Wall. Validation of the σ₁ Receptor 3D Model by Computer-Assisted Design, Synthesis, and Activity of New σ₁ Ligands
  作者：Erik Laurini、Domenico Marson、Valentina Dal Col、Maurizio Fermeglia、Maria Grazia Mamolo、Daniele Zampieri、Luciano Vio、Sabrina Pricl

  DOI：10.1021/mp300233y

  日期：2012.11.5

  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.