Bicyclic SARMs for Selective Androgen Receptor Modulation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current modulators of steroid binding nuclear hormone receptors, particularly androgen receptors, often have undesirable side effects and lack specificity, leading to ineffective treatment of androgen-related conditions such as sarcopenia and osteoporosis.
Innovation Solution
Development of novel bicyclic compounds with specific structural formulas that selectively modulate the androgen receptor, acting as agonists, partial agonists, or antagonists to treat androgen-related conditions with reduced impact on other androgen-responsive tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If synthetic androgens are administered to treat androgen-related conditions, then muscle mass and strength are improved, but liver damage and prostate cancer risks increase
Solution Approach 1:
The patent develops selective androgen receptor modulators (SARMs) with specific molecular structures that exhibit tissue-selective binding affinity. These compounds are designed to preferentially activate androgen receptors in skeletal muscle and bone tissues while having minimal activity in prostate and liver tissues, thereby providing localized therapeutic effects without systemic side effects
Solution Approach 2:
The invention modifies the chemical structure parameters of androgen compounds by introducing specific bicyclic core structures with varied substituent patterns. By adjusting molecular weight, lipophilicity, and steric configuration, the compounds achieve optimal binding selectivity for muscle and bone androgen receptors while reducing affinity for prostate and liver receptors
2Reliability
If conventional androgen modulators are used, then androgen receptor activity is increased, but tissue specificity is reduced leading to adverse effects
Solution Approach 1:
The SARMs described in the patent possess differential binding characteristics across various androgen receptor isoforms and tissue types. The molecular structure is optimized to create specific interaction patterns with androgen receptors in target tissues (muscle and bone) versus non-target tissues (prostate and liver), achieving reliable modulation only where needed
Solution Approach 2:
The invention segments the androgen receptor modulation effect by creating compounds that selectively engage specific receptor conformations or isoforms present in different tissues. This segmentation allows the same compound to activate receptors in muscle and bone while leaving prostate and liver receptors unactivated or minimally activated
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, R2′ R5, G, n and W are defined herein.