title: Synthesis of new piperazine-pyridazinone derivatives and their binding affinity toward alpha1-, alpha2-adrenergic and 5-HT1A serotoninergic receptors.
abstract: We report the design and synthesis of a new class of piperazine-pyridazinone analogues. The arylpiperazine moiety, the length of the spacer, and the terminal molecular fragment were varied to evaluate their influence in determining the affinity of the new compounds toward the alpha1-adrenergic receptor (alpha1-AR), alpha2-adrenergic receptor (alpha2-AR), and the 5-HT1A serotoninergic receptor (5-HT1AR). Biological data showed that most of the compounds have an alpha1-AR affinity in the nanomolar or subnanomolar range, while affinity toward the other two receptors was lower in most cases. However, several of the tested compounds also showed very good (in the nanomolar range) or moderate affinity toward the 5-HT1AR subtype.
authors.affiliation: Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa, Via Bonanno 6, I-56126 Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Betti
authors.forename: Marco
authors.initials: M
authors.lastname: Zanelli
authors.forename: Gino
authors.initials: G
authors.lastname: Giannaccini
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Manetti
authors.forename: Silvia
authors.initials: S
authors.lastname: Schenone
authors.forename: Giovannella
authors.initials: G
authors.lastname: Strappaghetti
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism*; D011724:Pyridazines / Q000138:chemical synthesis* / Q000378:metabolism*; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D010879:Piperazines; D011724:Pyridazines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D044282:Receptor, Serotonin, 5-HT1A; D000077489:Piperazine