title: Phenylpiperazinylalkylamino substituted pyridazinones as potent alpha(1) adrenoceptor antagonists.
abstract: QSAR models have been used for designing a series of compounds characterized by a N-phenylpiperazinylalkylamino moiety linked to substituted pyridazinones, which have been synthesized. Measurements of the binding affinities of the new compounds toward the alpha(1a)-, alpha(1b)-, and alpha(1d)-AR cloned subtypes as well as the 5-HT(1A) receptor have been done validating, at least in part, the estimations of the theoretical models. This study provides insight into the structure activity relationships of the alpha(1)-ARs ligands and their alpha(1)-AR/5-HT(1A) selectivity.
authors.affiliation: Istituto Chimico Farmaceutico e Tossicologico, Viale Abruzzi 42, 20131 Milano, Italy. daniela.barlocco@unimi.it
authors.forename: D
authors.initials: D
authors.lastname: Barlocco
authors.forename: G
authors.initials: G
authors.lastname: Cignarella
authors.forename: V D
authors.initials: VD
authors.lastname: Piaz
authors.forename: M P
authors.initials: MP
authors.lastname: Giovannoni
authors.forename: P G
authors.initials: PG
authors.lastname: De Benedetti
authors.forename: F
authors.initials: F
authors.lastname: Fanelli
authors.forename: F
authors.initials: F
authors.lastname: Montesano
authors.forename: E
authors.initials: E
authors.lastname: Poggesi
authors.forename: A
authors.initials: A
authors.lastname: Leonardi
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D016466:CHO Cells; D006224:Cricetinae; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1
chemical_list: D000317:Adrenergic alpha-Antagonists; D008024:Ligands; D010879:Piperazines; D011724:Pyridazines; D018340:Receptors, Adrenergic, alpha-1; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1