title: [1,2,4]Triazole derivatives as 5-HT(1A) serotonin receptor ligands.
abstract: A series of new 4-amino-3-[3-[4-(2-methoxy or nitro phenyl)-1-piperazinyl] propyl]thio]-5-(substitutedphenyl)[1,2,4]triazoles 11a-t was synthesized in order to obtain compounds with high affinity and selectivity for 5-HT(1A) receptor over the alpha(1)-adrenoceptor. A series of isomeric 4-amino-2-[3-[4-(2-methoxy or nitro phenyl)-1-piperazinyl]propyl]-5-(substitutedphenyl)-2,4-dihydro-3H[1,2,4]triazole-3-thiones 12a-r was also isolated and characterized. New compounds were tested to evaluate their affinity for 5-HT(1A) receptor and alpha(1)-adrenoceptor in radioligand binding experiments. As a general trend, triazoles 11a-t showed a preferential affinity for the 5-HT(1A) receptor whereas isomeric 2,4-dihydro-3H[1,2,4]triazole-3-thiones 12a-r preferentially bind to the alpha(1)-adrenoceptor site. Several molecules showed affinities in the nanomolar range and 4-amino-3-[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]thio]-5-(4-propyloxy-phenyl)[1,2,4]triazole (11o) was the most selective derivative for the 5-HT(1A) receptor (K(i) alpha(1)/K(i) 5-HT(1A)=55). The decrease in 5-HT(1A) receptor selectivity in 3-[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]thio]-5-(substitutedphenyl)[1,2,4] triazole 14a-b, lacking in the amino group in 4-position of the triazole ring, in comparison with their analogues in the series 11a-t, suggest that the amino function represents a critical structural feature in determining 5-HT(1A) receptor selectivity in this class of compounds.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Catania, viale A. Doria 6, 95125, Catania, Italy.
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Sarvà
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Romeo
authors.forename: Francesco
authors.initials: F
authors.lastname: Guerrera
authors.forename: Mariangela
authors.initials: M
authors.lastname: Siracusa
authors.forename: Loredana
authors.initials: L
authors.lastname: Salerno
authors.forename: Filippo
authors.initials: F
authors.lastname: Russo
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cagnotto
authors.forename: Mara
authors.initials: M
authors.lastname: Goegan
authors.forename: Tiziana
authors.initials: T
authors.lastname: Mennini
mesh_terms: D000818:Animals; D001671:Biochemistry / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008024:Ligands; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D013329:Structure-Activity Relationship; D013871:Thiones / Q000737:chemistry* / Q000378:metabolism*; D014230:Triazoles / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008024:Ligands; D018340:Receptors, Adrenergic, alpha-1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D013871:Thiones; D014230:Triazoles