Synthesis Of Phenasartan Analogue

Hypertension is a chronic disease, which is characterized by arterial pressure. It can cause a variety complications and become the important factor for heart disease.Angiotensin II receptor antagonist is a new class of anti-hypertensive drugs which acts on the renin-angiotensinsystem. There are more than ten kinds of losartan drugs on market,most of them are AT1 receptor antagonist. They are basically obtained by the structural modification and transformation of Losartan. Today, it’s still a hot method in the research of anti-hypertensive drugs.Phenasartan is a new kind of anti-hypertensive drugs, which is developed by our group.As a new angiotensin II / AT1 receptor antagonist, Phenasartannot only has higher antagonistic activity to AT1 receptors but also has a better anti-hypertensive effect thanlosartan. According to the modification and transformation methods of drug structural,two kinds of compounds were designed on the basis of our lead compound(phenasartan).One is 6-substituted benzimidazole amidecompounds, and another is the Sulfur-substituted Phenasartan Analogue. The two sorts of 6 target compounds were synthesized, including acylation reaction, alkylate reaction, hydrolysis reaction of ester, vulcanization reaction. All the noval structures of the intermediates were identified by boil、infrared and MS, and the target compounds also identified by1 H NMR and13 C NMR. The selectivity of synthetic route, experimental operation, results and discussion for each series of compounds were discussed respectively. The six new compounds canuse forthe activity screening.