WMS-1838 | 1264244-74-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异香豆素
• 英文名称: WMS-1838
• 英文别名: 3-(2-chloroethyl)-1'-(cyclohexylmethyl)-3H-spiro[[2]-benzofuran-1,4'-piperidine]；3-(2-Chloroethyl)-1''-(cyclohexylmethyl)-3H-spiro[[2]-benzofuran-1,4''-piperidine]；1-(2-chloroethyl)-1'-(cyclohexylmethyl)spiro[1H-2-benzofuran-3,4'-piperidine]
• CAS: 1264244-74-7
• 化学式: C₂₁H₃₀ClNO
• 分子量: 347.928
• InChiKey: NERFILQGCTVUJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  {2-[1'-(cyclohexylmethyl)-3H-spiro[[2]benzofuran-1,4'-piperidin]-3-yl]ethyl} p-toluenesulfonate 在 18-冠醚-6 、 potassium chloride 作用下， 以 乙腈 为溶剂， 以39%的产率得到WMS-1838
  参考文献：
  名称：

  Synthesis, pharmacological activity and structure affinity relationships of spirocyclic σ1 receptor ligands with a (2-fluoroethyl) residue in 3-position

  摘要：

  In order to develop a fluorinated radiotracer for imaging of sigma(1) receptors in the central nervous system a series of (2-fluoroethyl) substituted spirocyclic piperidines 3 has been prepared. In the key step of the synthesis 2-bromocinnamaldehyde acetal 5 was added to piperidones 6 with various substituents at the N-atom. Unexpectedly, this reaction led to 2-benzoxepines 8, which were contracted with acid to afford the spirocyclic 2-benzofuranacetaldehydes 9. The best yields were obtained, when the transformations up to the alcohols 10 were performed without isolation of intermediates. Generally the (2-fluoroethyl) derivatives 3 have higher sigma(1) affinity and sigma(1)/sigma(2) selectivity than the corresponding (3-fluoropropyl) derivatives 2. The most promising candidate for the development as radiotracer is the (2-fluoroethyl) derivative 3a (WMS-1828, fluspidine, 1'-benzyl-3-(2-fluoroethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]), which shows subnanomolar sigma(1) affinity (K-i = 0.59 nM) and excellent selectivity over the sigma(2) subtype (1331-fold) as well as some other receptor systems. The novel synthetic strategy also allows the systematic pharmacological evaluation of intermediate alcohols 10. Despite their high sigma(1) affinity (K-i = 6-32 nM) and selectivity the alcohols 10 are 10-30-fold less potent than the bioisosteric fluoro derivatives 3. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.11.013