Compounds of cadotril derivatives and angiotensin receptor antagonists and uses thereof

Abstract

The invention provides a complex of racecadotril derivatives and angiotensin receptor inhibitors and application of the complex. The complex is composed of the racecadotril derivatives and angiotensin receptor inhibitors. The components can be directly mixed or indirectly connected through hydrogen bonds, cocrystallized sodium hydrates formed by connecting through the hydrogen bonds have stable properties, and pharmacokinetic properties are obviously improved. Although the angiotensin receptor inhibitors have different action mechanisms from enkephalinase inhibitors, the complex formed by the racecadotril derivatives and angiotensin receptor inhibitors has an unexpected synergistic effect and has positive application prospects in the anti-heart-failure and anti-hypertension treatment fields.

Description

technical field [0001] The invention belongs to the field of drugs for treating diseases of the cardiovascular system, and particularly relates to a compound of a cardotril derivative and an angiotensin receptor antagonist and use thereof. 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, and its morbidity and mortality are high. 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 1.5% to 2.0%, and it can reach 6% to 10% for those over 65 years old. 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 infarction, cardiomyopathy, hemodynamic ov...

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Problems solved by technology

[0007] 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. For example, the applicant applied for a compound in August 2016, namely, CN106177960 A compound of an angiotensin receptor antagonist and a neprilysin inhibitor is disclosed, wherein a compound composed of cardotril and valsartan or irbesartan is disclosed, and the compound can be used for treating cardiomyopathy However, in further research by the applicant, the applicant found that after the compound was administered to mice for a period of time, angioedema still appeared, and the time for the two to exert their drug effects was short

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