Selective Androgen Receptor Modulators for Tissue-Specific Efficacy
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Solution Overview
Problem
Current compounds for modulating androgen receptors lack specificity and efficacy in treating various conditions related to muscle strength, bone density, and hormonal imbalances, with existing non-steroidal tricyclic compounds not fully addressing the need for tissue-specific androgen receptor modulation.
Innovation Solution
Development of specific compounds, such as those following Formula I, II, and III, which are selective androgen receptor modulators (SARMs) that can act as agonists, antagonists, or partial agonists, capable of binding to androgen receptors and modulating their activity, including those with a chlorine at position 9, to enhance muscle strength, bone density, and hormonal balance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If non-steroidal tricyclic compounds are used to modulate androgen receptors, then androgen receptor activity is modulated, but tissue-specificity and efficacy are insufficient
Solution Approach 1:
The patent applies local quality by introducing specific substituent patterns at defined positions (R1-R6) of the tricyclic core structure. Different substituents (halogens, alkyl groups, aryl groups) are placed at specific positions to create compounds with enhanced tissue-specific binding affinity. For example, chlorine at position 9 combined with specific R1-R6 substitutions creates compounds that selectively modulate androgen receptors in muscle and bone tissues while sparing other tissues.
Solution Approach 2:
The patent employs parameter changes by systematically varying chemical parameters (substituent types, positions, and combinations) of the tricyclic compound structure. By changing parameters such as adding fluorine atoms, modifying alkyl chain lengths, or introducing aromatic substituents at specific positions, the patent optimizes compounds for enhanced androgen receptor binding affinity and tissue-specific selectivity, thereby improving efficacy while maintaining adaptability.
2Adaptability or versatility
If existing androgen receptor modulators are used, then hormonal balance is affected, but specificity and side effect profile are inadequate
Solution Approach 1:
The patent uses local quality by placing specific functional groups at defined positions on the tricyclic scaffold. For instance, introducing electron-withdrawing groups like fluorine or chlorine at specific positions (e.g., position 9) while maintaining appropriate R1-R6 substituents creates compounds that selectively bind to androgen receptors with high affinity, achieving better hormonal balance modulation while reducing off-target effects and side effects through improved selectivity.
3Strength
If current compounds are used for treating muscle and bone conditions, then some therapeutic effect is achieved, but muscle strength and bone density improvement are insufficient
Solution Approach 1:
The patent applies parameter changes by optimizing the chemical structure parameters of the tricyclic compounds. By systematically varying substituents at R1-R6 positions and introducing specific groups (such as fluorine, chlorine, or aromatic rings) at key positions, the patent enhances the compounds' ability to activate androgen receptors in muscle and bone tissues. This structural optimization leads to improved therapeutic efficacy for increasing muscle strength and bone density compared to existing modulators.
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
These compounds effectively modulate androgen receptor activity, improving muscle strength, bone density, and hormonal balance, offering potential treatments for conditions like osteoporosis, sarcopenia, androgenic alopecia, and cancer, with enhanced specificity and reduced side effects compared to existing compounds.
Implementation Method 1
a ligand binds to an IR, forming a receptor/ligand complex
Data Source
AI summary
Provided herein are compounds that bind to androgen receptors and/or modulate activity of androgen receptors, and to methods for making and using such compounds. Also provided are compositions including such compounds and methods for making and using such compositions.