WMS-1830 | 1265916-71-9

• 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-1830
• 英文别名: 1'-butyl-3-(2-fluoroethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]；1''-Butyl-3-(2-fluoroethyl)-3H-spiro[[2]benzofuran-1,4''-piperidine]；1'-butyl-1-(2-fluoroethyl)spiro[1H-2-benzofuran-3,4'-piperidine]
• CAS: 1265916-71-9
• 化学式: C₁₈H₂₆FNO
• 分子量: 291.409
• InChiKey: PYPARTUORPDWGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  WMS-1824 在 二乙胺基三氟化硫 作用下， 以 二氯甲烷 为溶剂， 反应 16.5h， 以15.1 mg的产率得到WMS-1830
  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

文献信息

• Synthesis, pharmacological activity and structure affinity relationships of spirocyclic σ1 receptor ligands with a (2-fluoroethyl) residue in 3-position
  作者：Eva Große Maestrup、Christian Wiese、Dirk Schepmann、Peter Brust、Bernhard Wünsch

  DOI：10.1016/j.bmc.2010.11.013

  日期：2011.1

  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.