[en] The selectivity for 5-HT1A versus D4 receptors is significantly increased when the basic side chain of WAY-100635 is replaced by a 4-phenylpiperazine (3e) or a 4-phenyl-1,2,3,6-tetrahydropyridine moiety (3i). The 4-phenyl-1,2,3,6-tetrahydropyridine compounds (3i-l) have a higher affinity for 5-HT1A receptors than do the corresponding unsubstituted phenylpiperazine analogues (3e-h). Compounds 3e and 3i appear to be selective for 5-HT1A receptors over other relevant receptors and still behave as neutral antagonists.
Research center :
CIRM-Chimie Pharmaceutique
Disciplines :
Pharmacy, pharmacology & toxicology Chemistry
Author, co-author :
Mangin, Floriane; Université de Liège - ULiège > Département de Pharmacie > Chimie Pharmaceutique
Dilly, Sébastien ; Université de Liège - ULiège > Département de Pharmacie / Giga-Neurosciences > Chimie pharmaceutique / Pharmacologie
Joly, Benoît ; Université de Liège - ULiège > 2e an. master sc. pharma., fin spéc. prat. offici.
Scuvée-Moreau, Jacqueline ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Evans, Jon; University of North Carolina Chapel Hill Medical School > Department of Pharmacology School of Medicine > Division of Chemical Biology and Medicinal Chemistry
Setola, Vincent; University of North Carolina Chapel Hill Medical School > Department of Pharmacology School of Medicine > Division of Chemical Biology and Medicinal Chemistry
Roth, Bryan; University of North Carolina Chapel Hill Medical School > Department of Pharmacology School of Medicine > Division of Chemical Biology and Medicinal Chemistry
Liégeois, Jean-François ; Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Language :
English
Title :
Moderate chemical modifications of WAY-100635 improve the selectivity for 5-HT1A versus D4 receptors
Publication date :
2012
Journal title :
Bioorganic and Medicinal Chemistry Letters
ISSN :
0960-894X
eISSN :
1464-3405
Publisher :
Elsevier Science, Oxford, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Development of novel antipsychotic drugs
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] ULiège FSR - Université de Liège. Fonds spéciaux pour la recherche [BE]
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