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- Title
1-[(Imidazolidin-2-yl)imino]-1 H-indoles as new hypotensive agents: synthesis and in vitro and in vivo biological studies.
- Authors
Kornicka, Anita; Wasilewska, Aleksandra; Sączewski, Jarosław; Hudson, Alan L.; Boblewski, Konrad; Lehmann, Artur; Gzella, Karol; Belka, Mariusz; Sączewski, Franciszek; Gdaniec, Maria; Rybczyńska, Apolonia; Bączek, Tomasz
- Abstract
A series of 1-[(imidazolidin-2-yl)imino]-1 H-indole analogues of hypotensive α2-AR agonists, 1-[(imidazolidin-2-yl)imino]-1 H-indazoles, was synthesized and tested in vitro for their activities at α1- and α2-adrenoceptors as well as imidazoline I1 and I2 receptors. The most active 1-[(imidazolidin-2-yl)imino]-1 H-indoles displayed high or moderate affinities for α1- and α2-adrenoceptors and substantial selectivity for α2-adrenoceptors over imidazoline-I1 binding sites. The in vivo cardiovascular properties of indole derivatives 3 revealed that substitution at C-7 position of the indole ring may result in compounds with high cardiovascular activity. Among them, 7-fluoro congener 3g showed the most pronounced hypotensive and bradycardic activities in this experiment at a dose as low as 10 μg/kg i.v. Metabolic stability of the selected compounds of type 3 was determined using both in vitro and in silico approaches. The results indicated that these compounds are not vulnerable to rapid first-phase oxidative metabolism.
- Subjects
IMIDAZOLIDINES; INDOLE; INDAZOLES; ADRENERGIC receptors; IMINO compounds
- Publication
Chemical Biology & Drug Design, 2017, Vol 89, Issue 3, p400
- ISSN
1747-0277
- Publication type
Article
- DOI
10.1111/cbdd.12846