Synthesis Of Fimasartan And Its Derivatives

Hypertension is one of the common cardiovascular disease.There are about 270 million hypertensive patients in China.The prevalence rate is on the rise and it increases with age.If it is not treated,it will lead to serious complications such as cerebral hemorrhage,heart failure,and renal failure,which will seriously affect human health and even life.There are many drugs for the treatment of hypertension,and Sartan has become the first-line drug for the treatment of hypertension.Fimasartan is a novel angiotensin II receptor antagonist with selectivity for the angiotensin type 1 receptor(AT1)subtype;In a variety of types of hypertension it shows a rapid and effective compression effect.Preclinical and clinical studies show that fimasartan is well tolerated and is more secure than other Angiotensin Receptor Blocker(ARB)drugs,and is more effective in reducing cardiac diastolic blood pressure,it has the potential to become the best ARB drugs in the next twenty years.Fimasartan was studied in this paper.By analyzing and summarizing all the synthetic routes reported,we determineda new synthetic method.The intermediatesare relatively stable under acidic conditions.The new method did not generate new impurities and improved product quality and process operability,it is more conducive to industrial production.This study also used computeraided drug design to analyze the binding of derivativesand angiotensin II AT1 receptor and synthesized a series of derivatives of fimasartan.We also explored and optimized the synthetic processof thederivatives.In addition,the mode of interaction of derivatives of fimasartan with AT1 receptors in rabbit thoracic aorta was also characterized.In summary,the subject has improved the synthetic processof fimasartan and synthesized a series of its derivatives that based on fimasartan.We scored the derivativeswith the aid of computeraided drug design and the derivative which has the highest scorewas characterized in vitro.The result proved that the derivatives has good antihypertensive activity and has potential for further study.