Synthesis of azepino[1,2-a]benzimidazoles and imidazo[1,2-a]azepines

Abstract

Keywords: azepino[1,2-a]benzimidazole, J-bromodypnone, imidazo[1,2-a]azepine, cyclization.Amongst azepino[1,2-a]benzimidazole and imidazo[1,2-a]azepine condensed systems there are found highly active compounds which are proposed as antagonists of choline, histamine, and dopamine receptors [1][2][3][4], for the regulation of sodium or potassium ion transport through a cell membrane [3,5], and as antitumor agents [2]. However, the studied compounds structure in this series vary mainly in the azole part of the bicycle but the azepine part unsaturation degree and the effect of substituents in azepine ring on the compound properties has been little studied.Continuing our investigation of the heterocyclization of 4-bromo-1,3-diphenyl-2-buten-1-one (J-bromodypnone, 1a, Scheme 1) [6,7] we propose a method for the synthesis of 7,9-diarylazepino[1,2-a]benzimidazoles (2) and 6,8-diarylimidazo[1,2-a]azepines 3 and 4. Aiming the biological potential evaluation of compounds in this series we have calculated the spectrum of their biological activity using the PASS program (Prediction of Activity Spectra for Substances) [8][9][10]. Amongst a broad spectrum of predicted features the most widespread are their potential as ligands (substrates) of enzyme CYP2D16 (polypeptide 16, gene family 2, subfamily D of cytochrome P450) and as antagonists of the subtype A receptor of J-aminobutyric acid (GABA).Higher activity (Pa > 80%) is predicted for compounds with a hydrogenated azepine fragment. For these, a high likelihood of the appearance of dopamine receptor agonist and antidepressant properties should be noted.

New method for the annelation of a pyridine ring on derivatives of imidazole and benzimidazole

“…(Z)-4-Bromo-1,3-diphenyl-2-buten-1-one (1a) was prepared by method [18], (Z)-1,3-diaryl-4-bromo-2-buten-1-ones 1b-d by method [19]. 1-R-1H-Benzimidazoles and 1-R-1H-imidazoles were products of the company "Enamine".…”