New octahydroquinazoline derivatives: Synthesis and hypotensive activity

Several novel 1-(4-chlorophenyl)-7,7-dimethyl-1,2,3,4,5,6,7,8-octahydro-5-oxo-3-(substitutedphenyl)quinazoline derivatives (2–21) structurally similar to prazosin, were prepared using Mannich reaction of 3-(4-chlorophenylamino)-5,5-dimethyl-2-cyclohexenone (1) with different aromatic amines in the presence of formaline. The structures of the quinazoline derivatives were established using elemental and spectral analyses. Compounds 18, 20 and 21 were found to possess a high hypotensive effect through their expected α1-blocking activity like the clinically used drug prazosin but with advantageous of being did not cause reflex tachycardia and having prolonged duration of action when tested in adrenaline-induced hypertension in anaesthetized rats.

Graphical abstractApplication of Mannich reaction on 3-(4-chlorophenylamino)-5,5-dimethyl-2-cyclohexenone (1) led to the formation of octahydroquinazoline derivatives (2–21). Compounds 18, 20 and 21 showed a high hypotensive effect through their expected α1-blocking activity like the clinically used drug prazosin.Figure optionsDownload full-size imageDownload as PowerPoint slide