Moderate chemical modifications of WAY-100635 improve the selectivity for 5-HT1A versus D4 receptors.
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.
Laboratory of Medicinal Chemistry and Drug Research Center, University of Liège, Avenue de l'Hôpital, 1 (B36), B-4000 Liège 1, Belgium.
Floriane
F
Mangin
Sébastien
S
Dilly
Benoît
B
Joly
Jacqueline
J
Scuvée-Moreau
Jon
J
Evans
Vincent
V
Setola
Bryan L
BL
Roth
Jean-François
JF
Liégeois
D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D050638:Receptors, Dopamine D4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D010879:Piperazines; D011725:Pyridines; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D050638:Receptors, Dopamine D4; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide