Moderate chemical modifications of WAY-100635 improve the selectivity for 5-HT1A versus D4 receptors.

Floriane Mangin, Sébastien Dilly, Benoît Joly, Jacqueline Scuvée-Moreau, Jon Evans, Vincent Setola, Bryan L Roth, Jean-François Liégeois

Laboratory of Medicinal Chemistry and Drug Research Center, University of Liège, Avenue de l'Hôpital, 1 (B36), B-4000 Liège 1, Belgium.

Bioorganic & medicinal chemistry letters 2012 Jul 15

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The selectivity for 5-HT(1A) versus D(4) 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-HT(1A) receptors than do the corresponding unsubstituted phenylpiperazine analogues (3e-h). Compounds 3e and 3i appear to be selective for 5-HT(1A) receptors over other relevant receptors and still behave as neutral antagonists. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

Floriane Mangin, Sébastien Dilly, Benoît Joly, Jacqueline Scuvée-Moreau, Jon Evans, Vincent Setola, Bryan L Roth, Jean-François Liégeois. Moderate chemical modifications of WAY-100635 improve the selectivity for 5-HT1A versus D4 receptors. Bioorganic & medicinal chemistry letters. 2012 Jul 15;22(14):4550-4