Issue in Honor of Prof. Vincenzo Tortorella ARKIVOC 2004 (v) 312-324
Synthesis of new 5-phenyl[1,2,4]triazole derivatives as ligands for the 5-HT1A serotonin receptor
Loredana Salerno,a Mariangela Siracusa,a Francesco Guerrera,a Giuseppe Romeo,a Valeria Pittalà,a Maria Modica,a Tiziana Mennini,b and Filippo Russo*a
a Dipartimento di Scienze Farmaceutiche, Facoltà di Farmacia, Università degli Studi di Catania, Viale Andrea Doria, 6, 95125, Catania, Italy b Istituto di Ricerche Farmacologiche “Mario Negri”, Via Eritrea 62, 20157 Milano, Italy E-mail: l.salerno@unict.it
Dedicated to Professor Vincenzo Tortorella on his “Fuori Ruolo” Status (received 22 Dec 03; accepted 17 Apr 04; published on the web 23 Apr 04)
Abstract
A series of 4-amino-3-[[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]thio]-5-(substituted phenyl)[1,2,4]triazoles (5a-f) and the isomeric 4-amino-2-[2-[4-(2-methoxyphenyl)-1piperazinyl] ethyl]-5-(substitutedphenyl)-2,4-dihydro-3H[1,2,4]triazole-3-thiones (6a-f) and a series of 3-[[2-[4-(2-methoxy or 2-nitrophenyl)1-piperazinyl]ethyl]thio]-5-(substituted phenyl)[1,2,4]triazoles (8a-i) were synthesized with the aim of obtaining new selective 5-HT1A ligands, with reduced affinity for the a1-adrenoceptor subtypes. New compounds were tested in radioligand binding experiments where many of them showed a preferential affinity for the 5- HT1A receptor.
Keywords: 5-Phenyl[1,2,4]triazole, 5-HT1A serotonin receptor, a1-adrenoceptor subtypes, triazole ring alkylation
Introduction
5-HT1A serotonin receptors belong to the seven-transmembrane-domain (7-TM) receptor superfamily1 and mediate many physiological effects of the serotonin. Increasing evidence for the role of 5-HT1A receptor in psychiatric disorders, such as depression and anxiety,2-4 has encouraged the search for selective ligands.5-7 To date several potent 5-HT1A receptor ligands are known, however their potential use as drugs or pharmacological tools is often limited by their undesired affinity for other receptor types such as an example the dopaminergic D2 receptor and the a1-adrenoceptor (a1-AR). In particular, over the years many efforts have been made to discover 5-HT1A receptor ligands with reduced affinity for a1-AR.5-7
ISSN 1424-6376 Page 312 ©ARKAT USA, Inc
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