Studies on Novel Pyridine and 2-pyridone Derivatives of N-arylpiperazine as α-adrenoceptor Ligands

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 α_1-adrenoceptors, with exception of 6d, and are selective over α_2 receptor. The most potent compound 5f displayed 62-fold α_2/α_1 selectivity with K_i value of 27.3 nM for α_1 receptor. Selectivity of other ligands ranged from 6 to more than 146-fold. Hydrochlorides of selected compounds with the best α_1-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.

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