1‐[(Imidazolidin‐2‐yl)imino]‐1H‐indoles as new hypotensive agents: synthesis and in vitro and in vivo biological studies

Abstract

A series of 1-[(imidazolidin-2-yl)imino]-1H-indole analogues of hypotensive α -AR agonists, 1-[(imidazolidin-2-yl)imino]-1H-indazoles, was synthesized and tested in vitro for their activities at α - and α -adrenoceptors as well as imidazoline I and I receptors. The most active 1-[(imidazolidin-2-yl)imino]-1H-indoles displayed high or moderate affinities for α - and α -adrenoceptors and substantial selectivity for α -adrenoceptors over imidazoline-I 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.

Toward Acetylene Renaissance: Functionally Rich N-Aminoindoles from Acetylene Gas, Ketones, and Hydrazines in Two Steps

“…Therefore, synthesis and transformations of the indole systems are of continuous interest and the subject of many original papers and reviews. , One of the most important subfamilies of indoles is N -aminoindoles, whose derivatives exhibit promising biological activities . For example, among them is a commercial nootropic drug for the treatment of Alzheimer’s disease, e.g., besipirdine, N -propyl- N -(pyridin-4-yl)-1 H -indol-1-amine .…”