Synthesis and binding properties of novel selective 5-HT3 receptor ligands.
This work reports on the synthesis and affinities for the 5-HT(3) versus the 5-HT(4) receptor of new piperazinyl-substituted thienopyrimidine derivatives 20-45 with a view to identify potent and selective ligands for the 5-HT(3) receptor. Some of the new compounds show good affinity for the 5-HT(3) receptor and, notably, do not display any affinity for the 5-HT(4) receptor. 4-(4-Methyl-1-piperazinyl)-2-methylthio-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidine 31 exhibits the highest affinity for the 5-HT(3) receptor (Ki = 33 nM) and behaves as noncompetitive antagonist.
Modica
Maria
M
Dipartimento di Scienze Farmaceutiche, Università di Catania, viale A. Doria 6, 95125 Catania, Italy. mmodica@mbox.unict.it
Romeo
Giuseppe
G
Materia
Luisa
L
Russo
Filippo
F
Cagnotto
Alfredo
A
Mennini
Tiziana
T
Gáspár
Róbert
R
Falkay
George
G
Fülöp
Ferenc
F
D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011485:Protein Binding; D051381:Rats; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D018490:Serotonin Agents / Q000138:chemical synthesis* / Q000378:metabolism*; D013055:Spectrophotometry, Infrared
D008024:Ligands; D044406:Receptors, Serotonin, 5-HT3; D018490:Serotonin Agents