Chemical Biology and Drug Design p. 400 - 410 (2017)
Update date:2022-08-11
Topics:
Kornicka, Anita
Wasilewska, Aleksandra
S?czewski, Jaros?aw
Hudson, Alan L.
Boblewski, Konrad
Lehmann, Artur
Gzella, Karol
Belka, Mariusz
S?czewski, Franciszek
Gdaniec, Maria
Rybczyńska, Apolonia
B?czek, Tomasz
A series of 1-[(imidazolidin-2-yl)imino]-1H-indole analogues of hypotensive α2-AR agonists, 1-[(imidazolidin-2-yl)imino]-1H-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]-1H-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.
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