Mineralocorticoid Receptor Antagonists for Aldosterone Disorders
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Solution Overview
Problem
Current therapeutic options for hypertension and heart failure are suboptimal, and there is a need for additional interventions to effectively treat aldosterone-mediated disorders, including cardiovascular diseases and other conditions associated with excess aldosterone levels.
Innovation Solution
Development of compounds with Mineralocorticoid Receptor (MR) antagonist activity, specifically represented by certain chemical formulas and their pharmaceutically acceptable salts, which can be used to treat aldosterone-mediated disorders by antagonizing the aldosterone receptor.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If existing MR antagonists (spironolactone or eplerenone) are used to treat aldosterone-mediated disorders, then therapeutic benefit is achieved, but treatment options remain limited and suboptimal for certain patient populations
Solution Approach 1:
The patent segments the existing MR antagonist class into multiple distinct chemical series (e.g., indole, pyridine, pyrimidine, triazole derivatives), each with unique structural features and potentially differentiated pharmacological profiles. This segmentation provides diverse treatment options while maintaining therapeutic effectiveness through multiple chemical pathways.
Solution Approach 2:
The patent systematically varies key structural parameters of MR antagonists including heterocyclic ring types, substituent positions, and molecular weight ranges (150-500 Da). These parameter changes generate a library of compounds with optimized properties for different clinical scenarios, expanding adaptability while preserving core therapeutic benefits.
2Adaptability or versatility
If new chemical compounds are developed to expand treatment options, then adaptability improves, but development complexity and time increase
Solution Approach 1:
The patent designs a universal core scaffold (various heterocyclic rings with carboxamide or urea groups) that can bind to the MR with high affinity. Multiple functional groups and substituents are added to this universal core to create derivatives with potentially different pharmacokinetic profiles, allowing one core structure to serve multiple therapeutic functions.
Solution Approach 2:
The patent uses standardized intermediate compounds (e.g., heterocyclic carboxylic acids, amines, isocyanates) as building blocks that can be combined through routine chemical reactions to generate diverse final compounds. This intermediary approach simplifies the development process by breaking down complex molecule creation into manageable, repeatable steps.
Data Source
AI summary
The present invention is directed to compounds of the Formula (I) as well as pharmaceutically acceptable salts thereof, that are potentially useful for treating aldosterone-mediated diseases. The invention furthermore relates to processes for preparing compounds of the Formula (I), to their possible use in the treatment of the above mentioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of the Formula (I).