Document Detail


Synthesis, pharmacological evaluation and QSAR modeling of mono-substituted 4-phenylpiperidines and 4-phenylpiperazines.
MedLine Citation:
PMID:  23353756     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A series of mono-substituted 4-phenylpiperidines and -piperazines have been synthesized and their effects on the dopaminergic system tested in vivo. The structure activity relationship (SAR) revealed that the position and physicochemical character of the aromatic substituent proved to be critical for the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the brain of freely moving rats. In order to investigate how the structural properties of these compounds affect the response, a set of tabulated and calculated physicochemical descriptors were modeled against the in vivo effects using partial least square (PLS) regression. Furthermore, the binding affinities to the dopamine D(2) (DA D(2)) receptor and monoamine oxidase A (MAO A) enzyme were determined for a chosen subset and QSAR models using the same descriptors as in the in vivo model were produced to investigate the mechanisms leading to the observed DOPAC response. These models, in combination with a strong correlation between the levels of striatal DOPAC and the affinities to DA D(2) and MAO A, provides a comprehensive understanding of the biological response for compounds in this class.
Authors:
Fredrik Pettersson; Peder Svensson; Susanna Waters; Nicholas Waters; Clas Sonesson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-5
Journal Detail:
Title:  European journal of medicinal chemistry     Volume:  62C     ISSN:  1768-3254     ISO Abbreviation:  Eur J Med Chem     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0420510     Medline TA:  Eur J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  241-255     Citation Subset:  -    
Copyright Information:
Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Affiliation:
NeuroSearch Sweden AB, Arvid Wallgrens Backe 20, S-413 46 Göteborg, Sweden. Electronic address: fredrik_pettersson@mail.se.
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