Synthesis and properties of morpholino-substituted 2H-imidazole N-oxides as potential endothelioprotectors

Abstract

5-Morpholino-substituted 2H-imidazole 1-oxides have recently proven themselves as perspective molecules to counteract the pathological states associated with endothelial dysfunction. Among this series, an enhanced pharmacological activity has previously been demonstrated by a p-fluorophenyl-substituted derivative, implying the expediency of the scope expansion with regard to the related halogen-containing molecules. Herein, we report the straightforward synthesis of 7 novel morpholino-tethered 2H-imidazole oxides featuring various haloaryl moieties in their structures with the reaction yields ranging from 40 to 87%. The in silico analysis indicated the specific affinity of the obtained compounds to phosphodiesterase 5a (PDE5a), known as a vital enzyme for the cardiovascular system functioning. At the same time, the in vitro assay on the HEK-293 cell line showed generally low toxicity of the compounds under consideration, suggesting their eligibility for the further in vivo studies.