title: Studies on novel pyridine and 2-pyridone derivatives of N-arylpiperazine as α-adrenoceptor ligands.
abstract: This paper describes the synthesis of a series of new N-arylpiperazine derivatives of pyridine and 2-pyridone. The in vitro pharmacological study indicated that all of the compounds possess affinity towards α1-adrenoceptors, with exception of 6d, and are selective over α2 receptor. The most potent compound 5f displayed 62-fold α2/α1 selectivity with Ki value of 27.3 nM for α1 receptor. Selectivity of other ligands ranged from 6 to more than 146-fold. Hydrochlorides of selected compounds with the best α1-adrenoceptor affinity (7b, 7e, 7f, 8b) were tested in vivo (hypotensive activity test in rats) and the results proved their α-adrenoreceptor antagonistic activity. Furthermore, the lipophilicity of the investigated compounds has been assessed experimentally and in silico.
authors.forename: Marzena
authors.initials: M
authors.lastname: Baran
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kepczyńska
authors.forename: Marek
authors.initials: M
authors.lastname: Zylewski
authors.forename: Agata
authors.initials: A
authors.lastname: Siwek
authors.forename: Marek
authors.initials: M
authors.lastname: Bednarski
authors.affiliation: Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland. marzena.baran@uj.edu.pl.
authors.forename: Marek Tadeusz
authors.initials: MT
authors.lastname: Cegła
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry*; D011728:Pyridones / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D008024:Ligands; D010879:Piperazines; D011725:Pyridines; D011728:Pyridones; D018340:Receptors, Adrenergic, alpha-1; C017679:2-hydroxypyridine; C023666:pyridine