Document Detail

Enantioselective σ1 receptor binding and biotransformation of the spirocyclic PET tracer 1'-benzyl-3-(3-fluoropropyl)-3H-spiro[[2]benzofuran-1,4'-piperidine].
MedLine Citation:
PMID:  20845431     Owner:  NLM     Status:  In-Process    
It was shown that racemic (±)-2 [1'-benzyl-3-(3-fluoropropyl)-3H-spiro[[2]benzofuran-1,4'-piperidine], WMS-1813] represents a promising positron emission tomography (PET) tracer for the investigation of centrally located σ(1) receptors. To study the pharmacological activity of the enantiomers of 2, a preparative HPLC separation of (R)-2 and (S)-2 was performed. The absolute configuration of the enantiomers was determined by CD-spectroscopy together with theoretical calculations of the CD-spectrum of a model compound. In receptor binding studies with the radioligand [(3)H]-(+)-pentazocine, (S)-2 was thrice more potent than its (R)-configured enantiomer (R)-2. The metabolic degradation of the more potent (S)-enantiomer was considerably slower than the metabolism of (R)-2. The structures of the main metabolites of both enantiomers were elucidated by determination of the exact mass using an Orbitrap-LC-MS system. These experiments showed a stereoselective biotransformation of the enantiomers of 2.
Christian Wiese; Eva Grosse Maestrup; Dirk Schepmann; Stefan Grimme; Hans-Ulrich Humpf; Peter Brust; Bernhard Wünsch
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-15
Journal Detail:
Title:  Chirality     Volume:  23     ISSN:  1520-636X     ISO Abbreviation:  Chirality     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8914261     Medline TA:  Chirality     Country:  United States    
Other Details:
Languages:  eng     Pagination:  148-54     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Wiley-Liss, Inc.
Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Hittorfstraße 58-62, Münster, Germany.
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