Synthesis and pharmacological study of some new octahydroquinazoline derivative as hypotensive agents

ABSTRACT

New 1,2,3,4,5,6,7,8-octahydro-5-oxo-1-[4-substituted phenyl]-3-substituted phenylquinazolines and their 7,7-dimethyl derivatives were prepared through Mannich reaction of 3-[4-substituted phenylamino]-2-cyclohexenones and their 5,5-dimethyl derivatives, respectively. Some of the new compounds were tested for their hypotensive activity in normotensive urethane-anesthetized rats in comparison with prazosin. A number of the tested compounds, notably 11, 13, 15, 19, 30 and 34 showed a significant hypotensive activity at i.p. doses of 2.5 and /or 5 mg/kg. The effects of various substitutes at 1 and /or 3 positions of the quinazoline skeleton on the activity were investigated. Compound 34 at i.p. dose of 2.5 mg/kg and 11, 13, 19 and 30 at 5 mg/kg showed alpha-adrenoceptor blocking activity in adrenaline-induced hypertension in anesthetized rats and their order of potency after 30 minutes of injection was 34 > prazosin > 11 > 13 > 30 > 19