Article (Scientific journals)
Molecular modeling study of 4-phenylpiperazine and 4-phenyl-1,2,3,6-tetrahydropyridine derivatives: A new step towards the design of high-affinity 5-HT1A ligands
Dilly, Sébastien; Graulich, Amaury; Liégeois, Jean-François
2010In Bioorganic and Medicinal Chemistry Letters, 20 (2), p. 1118-1123
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Keywords :
5-HT1A receptors; Arylpiperazine; 1,2,3,6-Tetrahydropyridine; Conformational analysis; CH–Pi interaction
Abstract :
[en] The main feature of many drugs having a 5-HT1A affinity is the presence of an arylpiperazine moiety. Indeed, the protonated nitrogen and the aromatic ring of the arylpiperazine compounds are considered crucial for the interaction with the receptor. However, the replacement of the piperazine moiety by a 1,2,3,6-tetrahydropyridine ring in 4-arylpiperazine-ethyl carboxamide derivatives was recently shown to be highly favourable for 5-HT1A affinity. In order to better understand the favourable effect of this chemical modification, we performed a conformational analysis of these compounds mainly based on the position of the phenyl ring relative to the piperazine and tetrahydropyridine moiety. In the piperazine compounds, the phenyl ring preferentially adopts a perpendicular orientation, whereas an almost planar orientation seems to be the most favourable conformation for the tetrahydropyridine compounds. Therefore, this conformational difference appears as a key for a better interaction with the receptor binding site. This result will serve for the designing high-affinity 5-HT1A ligands.
Research center :
Laboratory of Medicinal Chemistry, Drug Research Center
Disciplines :
Computer science
Pharmacy, pharmacology & toxicology
Author, co-author :
Dilly, Sébastien ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Graulich, Amaury
Liégeois, Jean-François ;  Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Language :
English
Title :
Molecular modeling study of 4-phenylpiperazine and 4-phenyl-1,2,3,6-tetrahydropyridine derivatives: A new step towards the design of high-affinity 5-HT1A ligands
Publication date :
January 2010
Journal title :
Bioorganic and Medicinal Chemistry Letters
ISSN :
0960-894X
eISSN :
1464-3405
Publisher :
Elsevier Science, Oxford, United Kingdom
Volume :
20
Issue :
2
Pages :
1118-1123
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
ULg FSR - Université de Liège. Fonds spéciaux pour la recherche [BE]
Fondation Léon Fredericq [BE]
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