Fused Azadecalin Glucocorticoid Receptor Modulators
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Solution Overview
Problem
Current methods for modulating glucocorticoid receptors lack effective compositions and methods to address various physiological and pathological conditions associated with cortisol levels, such as stress, trauma, and depression, with existing antagonists like mifepristone having limitations in affinity and specificity.
Innovation Solution
Development of fused azadecalin compounds that can bind to glucocorticoid receptors, acting as modulators to either agonize or antagonize the receptor activity, thereby treating disorders related to cortisol imbalances.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antagonists like mifepristone are used to block glucocorticoid receptors, then receptor blocking activity is achieved, but affinity and specificity are limited
Solution Approach 1:
The patent applies parameter changes by systematically modifying the chemical structure of glucocorticoid receptor modulators through variations in ring J substituents (different heteroaryl groups, fusion patterns, and positions) to optimize both affinity and specificity parameters simultaneously, resolving the contradiction between achieving reliable blocking activity and improving measurement precision of binding characteristics
2Measurement precision
If new fused azadecalin compounds are developed to improve affinity and specificity, then receptor modulating capability is enhanced, but composition complexity increases
Solution Approach 1:
The patent employs universality by creating a multi-functional heteroaryl group (ring J) that can be configured in multiple ways (different fusion patterns, heteroatom compositions, and substitution positions) to achieve various affinity and specificity profiles from a single core azadecalin structure, thereby enhancing receptor modulating capability without proportionally increasing overall composition complexity
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The fused azadecalin compounds effectively modulate glucocorticoid receptors, providing therapeutic benefits by either activating or blocking receptor activity, thus treating disorders associated with cortisol imbalances, offering a potential alternative to existing antagonists.
Implementation Method 1
fused azadecalin compounds that can bind to glucocorticoid receptors, acting as modulators to either agonize or antagonize the receptor activity
Data Source
AI summary
The present invention provides heteroaryl ketone fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators, including their use for treating amyotrophic lateral sclerosis (ALS).