title: Synthesis and binding properties of new long-chain 4-substituted piperazine derivatives as 5-HT₁A and 5-HT₇ receptor ligands.
abstract: New long-chain 4-substituted piperazines linked to a thienopyrimidine or a quinazoline system were synthesized and tested for their binding properties on human cloned 5-HT1A and 5-HT7 serotonin receptors. Some structural modifications, concerning tree main portions, that is, terminal fragment, chain length, and aryl substituents, were examined. The 2- and 3-substituted thienopyrimidinone and quinazolinone systems were selected as terminal fragment and a chain length of four or five methylene units was set. Explored aryl substituents were phenyl, phenylmethyl, 3- or 4-chlorophenyl, and 2-ethoxyphenyl. Title compounds showed affinity for 5-HT1A and 5-HT7 receptors. In particular, 2-ethoxyphenyl derivatives 40 and 45 displayed Ki values in the nanomolar range on both receptors, acting as dual ligands.
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Catania, viale A. Doria 6, Catania 95125, Italy. Electronic address: mmodica@unict.it.
authors.forename: Maria N
authors.initials: MN
authors.lastname: Modica
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Catania, viale A. Doria 6, Catania 95125, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Intagliata
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Catania, viale A. Doria 6, Catania 95125, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Pittalà
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Catania, viale A. Doria 6, Catania 95125, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Salerno
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Catania, viale A. Doria 6, Catania 95125, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Siracusa
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', via La Masa 19, Milano 20156, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cagnotto
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', via La Masa 19, Milano 20156, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Catania, viale A. Doria 6, Catania 95125, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Romeo
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry; D011799:Quinazolines / Q000737:chemistry; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D010879:Piperazines; D011743:Pyrimidines; D011799:Quinazolines; D011985:Receptors, Serotonin; C104425:serotonin 7 receptor; C476003:thienopyrimidine; D044282:Receptor, Serotonin, 5-HT1A; D000077489:Piperazine
keywords: 5-HT(1A); 5-HT(7); Binding properties; Ligands; Serotonin