Phenylpiperazinylalkylamino substituted pyridazinones as potent alpha(1) adrenoceptor antagonists.
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.
Barlocco
D
D
Istituto Chimico Farmaceutico e Tossicologico, Viale Abruzzi 42, 20131 Milano, Italy. daniela.barlocco@unimi.it
Cignarella
G
G
Piaz
V D
VD
Giovannoni
M P
MP
De Benedetti
P G
PG
Fanelli
F
F
Montesano
F
F
Poggesi
E
E
Leonardi
A
A
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
D000317:Adrenergic alpha-Antagonists; D008024:Ligands; D010879:Piperazines; D011724:Pyridazines; D018340:Receptors, Adrenergic, alpha-1; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1