Novel sigma(1) Receptor Ligands by Oxa-Pictet-Spengler Reaction of Pyrazolylethanol

作者：Schlaeger Torsten; Schepmann Dirk; Wuensch Bernhard

来源：Synthesis, 2011, (24): 3965-3974.

DOI：10.1055/s-0031-1289607

• sigma(1) receptor ligands
• oxa-Pictet-Spengler reaction
• annulated pyrazoles
• pyrazolylethanol
• structure affinity relationships

The oxa-Pictet-Spengler reaction of 2-(1-phenylpyrazol-5-yl)ethanol required the weak acid pyridinium p-toluenesulfonate to provide pyrano[4,3-c]pyrazoles with additional functional groups in the side chain. These functional groups allow the introduction of various amino substituents into the side chain in position 4. In receptor binding studies the aminoethyl-substituted pyranopyrazoles revealed higher sigma(1) receptor affinities and sigma(1)/sigma(2) selectivities than the shorter aminomethyl homologues. The pyranopyrazole bearing the phenylpiperidine substituent (K-i = 0.99 nM) represents the most potent and that bearing the piperidine substituent the most selective (sigma(1)/sigma(2) = 180) sigma(1) ligands of this series of compounds.

• 出版日期2011-12