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Updated: May 21, 2026

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Moderate chemical modifications of WAY-100635 improve the selectivity for 5-HT1A versus D4 receptors
Floriane Mangin1, Sébastien Dilly, Benoît Joly
1Laboratory of Medicinal Chemistry and Drug Research Center, University of Liège, Avenue de l'Hôpital, 1 (B36), B-4000 Liège 1, Belgium.
Abstract:
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.
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