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.
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.
Betti
Laura
L
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa, Via Bonanno 6, 56126, Pisa, Italy.
Floridi
Monia
M
Giannaccini
Gino
G
Manetti
Fabrizio
F
Strappaghetti
Giovannella
G
Tafi
Andrea
A
Botta
Maurizio
M
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
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D011724:Pyridazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1