title: Design and synthesis of new homo and hetero bis-piperazinyl-1-propanone derivatives as 5-HT7R selective ligands over 5-HT1AR.
abstract: In this work we report the discovery of new homo and hetero bis-piperazinyl-1-propanone derivatives as selective ligands for 5-HT7 over 5-HT1A receptor. These newly synthesized compounds possess a 4-arylpiperazine linked through an acyl spacer to another substituted piperazine system and were tested for their binding properties on human cloned 5-HT1A and 5-HT7 serotonin receptors. Among these, phenyl, 4- and 2-chlorophenyl, 2-methoxyphenyl, 2-pyridyl, and 2-pyrimidyl derivatives 15, 24, 25, and 27-29 displayed nanomolar affinity values for the 5-HT7 receptor (Ki 23.5-52.0nM) and no affinity for the 5-HT1A receptor.
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Catania, viale A. Doria 6, Catania 95125, Italy. Electronic address: s.intagliata@studium.unict.it.
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: 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: 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: D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008024:Ligands; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D011407:Propane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D011485:Protein Binding; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C078730:serotonin 5 receptor; C104425:serotonin 7 receptor; D000077489:Piperazine; D011407:Propane
keywords: 5-HT(7) selective ligands; Bivalent ligand approach; Hetero bis-piperazine; Homo bis-piperazine; Serotonin receptors