Compound prepared from angiotensin receptor antagonist and enkephalinase inhibitor and application of compound

Abstract

The invention provides a compound prepared from an angiotensin receptor antagonist and an enkephalinase inhibitor and application of the compound. The compound is prepared from the angiotensin receptor antagonist and the enkephalinase inhibitor, the angiotensin receptor antagonist and the enkephalinase inhibitor can be directly mixed or indirectly connected through hydrogen bonds, and a co-crystallized sodium hydrate prepared through hydrogen bond connection is more stable in property and significant in pharmacokinetic property; although the action mechanism of the angiotensin receptor antagonist and the action mechanism of the enkephalinase inhibitor are different, the compound prepared from the angiotensin receptor antagonist and the enkephalinase inhibitor has an unexpected synergistic effect and has a positive application prospect in the anti-heart-failure and anti-hypertension treatment field.

Description

technical field [0001] The invention belongs to the field of drugs for treating diseases of the cardiovascular system, in particular to a compound of an angiotensin receptor antagonist and a neprilysin inhibitor and its application. Background technique [0002] Heart failure (referred to as heart failure) is a complex clinical symptom group, which is a severe stage of various heart diseases. Its incidence rate is high, and its 5-year survival rate is similar to that of malignant tumors. The incidence of heart failure will continue to increase in the near future, and it is becoming the most important cardiovascular disease in the 21st century. [0003] According to foreign statistics, the prevalence of heart failure in the population is about 1.5E-2.0E, and it can reach 6%-10% over the age of 65. In the past 40 years, the death rate caused by heart failure has increased by 6 times. Heart failure is the initial myocardial injury due to any cause (such as myocardial infarctio...

AI Technical Summary

Problems solved by technology

[0009] However, there are currently no clinically effective drugs for the treatment of heart failure and hypertension, and most drugs have unavoidable side effects while relieving symptoms of heart failure and hypertension

And the order of a single drug is prone to tolerance. In order to treat heart failure and hypertension more effectively, some compounds have been developed in the prior art, such as an angiotensin receptor antagonist and NEP inhibitor disclosed in CN101098689 The drug combination product, which consists of valsartan and (2R,4S)-5-biphenyl-4-yl-5-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester ( sacubitril), this combination product was listed in the United States and Europe in 2015, and is clinically used for the treatment of chronic heart failure; but the prior art has not yet disclosed the complex composed of angiotensin receptor antagonist and cansatril , and did not disclose whether the complex has the effect of anti-heart failure and hypertension. In addition, the complex composed of angiotensin receptor antagonist and canzatril has no definite crystal structure, resulting in unstable properties of the complex. low bioavailability

Images