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.
Keywords: α-adrenoceptor ligands, N-arylpiperazine derivatives, lipophilicity, pyridine, 2-pyridone.
Medicinal Chemistry
Title:Studies on Novel Pyridine and 2-pyridone Derivatives of N-arylpiperazine as α-adrenoceptor Ligands
Volume: 10 Issue: 2
Author(s): Marzena Baran, Elzbieta Kepczynska, Marek Zylewski, Agata Siwek, Marek Bednarski and Marek Tadeusz Cegla
Affiliation:
Keywords: α-adrenoceptor ligands, N-arylpiperazine derivatives, lipophilicity, pyridine, 2-pyridone.
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.
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Cite this article as:
Baran Marzena, Kepczynska Elzbieta, Zylewski Marek, Siwek Agata, Bednarski Marek and Cegla Tadeusz Marek, Studies on Novel Pyridine and 2-pyridone Derivatives of N-arylpiperazine as α-adrenoceptor Ligands, Medicinal Chemistry 2014; 10 (2) . https://dx.doi.org/10.2174/0929867320999131122114922
DOI https://dx.doi.org/10.2174/0929867320999131122114922 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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