Bicyclic Androgen Receptor Modulators Tissue Selectivity
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Solution Overview
Problem
There is a need for selective modulators of steroid binding nuclear hormone receptors, particularly non-steroidal, non-toxic tissue-selective androgen receptor modulators that activate the androgen receptor in skeletal muscle with minimal effect on other androgen-responsive tissues, as existing modulators often have undesirable side effects.
Innovation Solution
Development of bicyclic compounds with a specific formula that modulate the function of nuclear hormone receptors, including pharmaceutical compositions and methods for treating androgen receptor-associated conditions, by administering therapeutically effective amounts of these compounds to patients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If synthetic androgens are administered to treat androgen receptor-associated conditions, then therapeutic effect is achieved, but liver damage and other side effects occur
Solution Approach 1:
The patent develops tissue-selective androgen receptor modulators (TAMs) that exhibit differential activity in different tissues. The bicyclic compounds are designed to preferentially activate androgen receptors in skeletal muscle while having minimal effect on prostate and liver tissues, thereby achieving therapeutic benefits locally without systemic side effects
Solution Approach 2:
The patent modifies the chemical structure from traditional steroidal androgens to non-steroidal bicyclic compounds. This structural parameter change fundamentally alters the receptor binding profile and tissue selectivity, allowing activation of androgen receptors in target tissues while avoiding harmful interactions with liver enzymes and prostate receptors
2Reliability
If conventional androgen modulators are used, then androgen receptor activation occurs, but tissue-selectivity is poor leading to adverse effects on multiple androgen-responsive tissues
Solution Approach 1:
The bicyclic compounds are designed with specific molecular features that confer tissue-selective binding properties. The compounds preferentially interact with androgen receptors in skeletal muscle tissue due to local receptor isoform differences and co-regulator availability, while showing reduced affinity for androgen receptors in prostate and other sensitive tissues
Solution Approach 2:
The patent segments the androgen receptor modulation effect by tissue type. The bicyclic compounds create distinct pharmacological zones: high activation in skeletal muscle, minimal activation in prostate, and selective activation in bone tissue, thereby achieving spatial segmentation of therapeutic effects
3Duration of action of stationary object
If long-term administration of androgen modulators is performed, then sustained therapeutic effect is achieved, but cumulative side effects increase
Solution Approach 1:
The tissue-selective bicyclic compounds maintain sustained therapeutic effects in skeletal muscle through continuous but localized androgen receptor activation. Because the compounds do not significantly activate androgen receptors in liver and prostate tissues, cumulative toxicities in these organs are minimized even during long-term administration
Solution Approach 2:
The patent converts the potential harm of long-term androgen exposure into a benefit by using tissue-selective modulation. The compounds leverage the body's natural androgen signaling pathways in target tissues while avoiding activation in sensitive tissues, thereby transforming what would be a harmful cumulative exposure into a safe, sustained therapeutic effect
Data Source
AI summary
The present invention relates to bicyclic compounds according to formula I, pharmaceutical compositions containing such compounds and methods of using such compounds in the treatment of androgen receptor-associated conditions, such as age-related diseases, for example sarcopenia,wherein R1, R2, R5, X, Y and n are defined herein.