Phenyl-Substituted Dihydronaphthyridine Compounds for Mineralocorticoid Receptor Antagonism
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Solution Overview
Problem
Current treatments for hypertension, heart failure, and other aldosterone-related diseases are not fully effective, leaving a significant unmet medical need for alternative pharmacological interventions.
Innovation Solution
Development of phenyl-substituted dihydronaphthyridine compounds with mineralocorticoid receptor (MR) antagonism, which can be used to treat or prevent conditions such as aldosteronism hyperplasia, diabetic nephropathy, hypertension, heart failure, and other cardiovascular diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for hypertension and heart failure are used, then some therapeutic effect is achieved, but they are not fully effective and leave significant unmet medical need
Solution Approach 1:
The patent modifies the chemical structure of known mineralocorticoid receptor antagonists by introducing phenyl substituents at specific positions (R2, R3, R4) of the dihydronaphthyridine core. This structural parameter change enhances the compound's ability to antagonize the mineralocorticoid receptor, providing more effective treatment for hypertension, heart failure, and other aldosterone-related diseases where current therapies are insufficient
2Reliability
If mineralocorticoid receptor antagonists are used to treat aldosteronism hyperplasia and aldosterone escape, then MR activity is reduced, but the treatments are not fully effective for refractory hypertension
Solution Approach 1:
The patent creates composite chemical structures by combining the dihydronaphthyridine core with phenyl substituents and various functional groups at positions R1-R9. This composite molecular design produces compounds with enhanced mineralocorticoid receptor antagonism activity, effectively addressing refractory hypertension and aldosterone escape that respond poorly to conventional single-structure antagonists
Data Source
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AI summary
The present invention discloses phenyl-substituted dihydronaphthyridine compounds a preparation therefor and a use thereof, and belongs to the technical field of medicine. The compounds disclosed in the present invention are represented by formula I, and can be used as a mineralocorticoid receptor antagonist for treating, preventing or alleviating aldosteronism hyperplasia, diabetic nephropathy, hypertension, heart failure (comprising chronic heart failure, etc.), sequelae of myocardial infarction, liver cirrhosis, renal failure, stroke and other diseases in patients.