| Enantioselective σ1 receptor binding and biotransformation of the spirocyclic PET tracer 1'-benzyl-3-(3-fluoropropyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]. | |
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MedLine Citation:
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PMID: 20845431 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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. |
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Authors:
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Christian Wiese; Eva Grosse Maestrup; Dirk Schepmann; Stefan Grimme; Hans-Ulrich Humpf; Peter Brust; Bernhard Wünsch |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-15 |
Journal Detail:
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Title: Chirality Volume: 23 ISSN: 1520-636X ISO Abbreviation: Chirality Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-04 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8914261 Medline TA: Chirality Country: United States |
Other Details:
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Languages: eng Pagination: 148-54 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Wiley-Liss, Inc. |
Affiliation:
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Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Hittorfstraße 58-62, Münster, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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