Comparative molecular field analysis of some pyridazinone-containing alpha1-antagonists.
Diverse series of piperazines linked at N1 to 4, 5, or 6 positions of 3-(2H)-pyridazinone ring and at N4, by a suitable alkyl spacer, to some classical alpha1-adrenoceptor pharmacophore moieties, were tested in vitro for their alpha1-adrenoceptor antagonist activity. The modeling of their biological activity (pKb) by comparative molecular field analysis led to the development of a statistically significant partial least squares (PLS) model able to detect at 3-D level the main physicochemical interactions responsible for alpha1-adrenoceptor antagonist activity.
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Dipartimento Farmaco-Chimico, Università di Bari, Italy.
Carrieri
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Strappaghetti
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Corsano
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Barbaro
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Carotti
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D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D013329:Structure-Activity Relationship
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D011724:Pyridazines; D018340:Receptors, Adrenergic, alpha-1