Pd-catalyzed direct C–H bond functionalization of spirocyclic σ1 ligands: generation of a pharmacophore model and analysis of the reverse binding mode by docking …

C Meyer, D Schepmann, S Yanagisawa…

Index: Meyer, Christina; Neue, Benedikt; Schepmann, Dirk; Yanagisawa, Shuichi; Yamaguchi, Junichiro; Wuerthwein, Ernst-Ulrich; Itami, Kenichiro; Wuensch, Bernhard Organic and Biomolecular Chemistry, 2011 , vol. 9, # 23 p. 8016 - 8029

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Citation Number: 33

Abstract

To explore the hydrophobic binding region of the σ1 receptor protein, regioisomeric spirocyclic thiophenes 9–11 were developed as versatile building blocks. Regioselective α- and β-arylation using the catalyst systems PdCl2/bipy/Ag2CO3 and PdCl2/P [OCH (CF3) 2] 3/Ag2CO3 allowed the introduction of various aryl moieties at different positions in the last step of the synthesis. The increasing σ1 affinity in the order 4< 5/6< 7/8 indicates that the ...