Selective Androgen Receptor Modulators Tissue Selectivity
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current androgen replacement therapies have significant side effects and lack tissue-selective activity, necessitating the development of compounds that can modulate the androgen receptor with reduced side effects and improved therapeutic benefits.
Innovation Solution
Non-steroidal compounds, specifically selective androgen receptor modulators (SARMs), are developed to selectively bind to the androgen receptor, mimicking or inhibiting the effects of testosterone, offering tissue-selective anabolic activity without the adverse effects of traditional androgen therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If traditional androgen replacement therapy is used, then muscle mass and strength are improved, but side effects such as prostate cancer, liver toxicity, and increased hematocrit occur
Solution Approach 1:
The patent applies the local quality principle by designing SARMs that exhibit tissue-selective androgenic activity. Different compounds in the series demonstrate preferential binding affinity to androgen receptors in specific tissues (skeletal muscle, bone, liver, prostate) based on their molecular structure variations. This allows the therapy to provide anabolic benefits in target tissues while minimizing androgenic effects in tissues where side effects occur, such as the prostate and liver.
Solution Approach 2:
The patent employs parameter changes by systematically modifying molecular parameters of the androgen receptor modulators, including substituent groups (R1-R6), stereochemistry, and molecular weight. These parameter variations tune the pharmacological profile of each compound to optimize the ratio of anabolic effects to androgenic side effects, enabling selective modulation of tissue response to androgen therapy.
2Strength
If androgen therapy is administered, then bone mineral density is improved, but prostate cancer risk increases
Solution Approach 1:
The patent applies local quality by designing compounds with differential tissue selectivity. Specific substituents on the core molecular structure enhance binding affinity to androgen receptors in bone tissue while reducing affinity for prostatic androgen receptors. This spatial selectivity in molecular interaction allows bone density improvement without stimulating prostate cancer growth.
Solution Approach 2:
The SARMs act as intermediary molecules that mediate androgen receptor activation in a tissue-specific manner. Rather than directly activating all androgen receptors uniformly, these compounds serve as selective mediators that preferentially trigger anabolic signaling in bone tissue while acting as antagonists or having minimal effect on prostatic androgen receptors, thereby decoupling beneficial from harmful effects.
3Ease of operation
If testosterone therapy is used, then cognitive function and mood are improved, but acne and hirsutism occur
Solution Approach 1:
The patent applies local quality by designing SARMs with selective tissue distribution and receptor binding characteristics. The molecular structures are optimized to preferentially activate androgen receptors in the central nervous system (improving cognitive function and mood) while having minimal affinity for androgen receptors in sebaceous glands and hair follicles, thereby avoiding acne and hirsutism side effects.
4Reliability
If current androgen therapies are administered, then treatment benefits are achieved, but tissue-selective activity is lacking
Solution Approach 1:
The patent systematically applies local quality by creating a series of analogs with varying substituent patterns that confer different tissue selectivity profiles. Each compound in the series can be tailored to preferentially act on specific androgen receptor isoforms or tissue types, providing reliable treatment benefits with adapted tissue-selective activity based on clinical needs.
Solution Approach 2:
The patent employs universality by designing a core molecular scaffold that can perform multiple functions depending on substituent configuration. The same basic structure can be adapted to provide anabolic effects in muscle, bone, or brain tissue by changing R1-R6 groups, making the compound class universally applicable across different androgen-responsive tissues with tunable selectivity.
Data Source
AI summary
This invention relates to non-steroidal compounds that are modulators of androgen receptor, and also to the methods for the making and use of such compounds.