title: alpha1-Adrenoceptor antagonists. 5. Pyridazinone-arylpiperazines. Probing the influence on affinity and selectivity of both ortho-alkoxy groups at the arylpiperazine moiety and cyclic substituents at the pyridazinone nucleus.
abstract: Our previous work on pyridazinone-arylpiperazine derivatives suggested some structural features that a compound should have to show high affinity and good selectivity for alpha(1) adrenoceptors (AR) with respect to alpha(2)-AR. Accordingly, two classes of new alkoxyphenylpiperazinylheptylpyridazinones were designed and synthesized to evaluate the effect of the alkoxy substituent on affinity and selectivity. As expected, affinity increased with larger alkoxy groups. Affinity values are all comparable with that of the reference compound (prazosin), with the exception of compound 1c found 4.5-fold more active than prazosin.
authors.affiliation: Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa, Via Bonanno 6, 56126, Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Betti
authors.forename: Monia
authors.initials: M
authors.lastname: Floridi
authors.forename: Gino
authors.initials: G
authors.lastname: Giannaccini
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Manetti
authors.forename: Giovannella
authors.initials: G
authors.lastname: Strappaghetti
authors.forename: Andrea
authors.initials: A
authors.lastname: Tafi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003500:Cyclization; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D011724:Pyridazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1