Selective Androgen Receptor Modulators for Muscle Growth
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Solution Overview
Problem
Current androgen therapies often have undesirable side effects such as prostate stimulation and increased acne, while lacking tissue-selective effects, necessitating the development of novel selective androgen receptor modulators (SARMs) that minimize these issues while maintaining muscle growth and therapeutic benefits.
Innovation Solution
Development of specific compounds, such as those described by the formula I, which act as SARMs by modulating the androgen receptor with a structure that allows for selective activity on muscle tissue without stimulating the prostate, thereby mimicking the effects of testosterone or dihydrotestosterone while reducing side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If androgen agonists (testosterone, dihydrotestosterone) are used to promote muscle growth and bone density, then anabolic effects are improved, but prostate stimulation and acne occur
Solution Approach 1:
The patent applies local quality by designing androgen receptor modulators with specific molecular structures (formula I compounds featuring substituted phenyl rings, heteroaryl groups, and specific substituent patterns) that selectively bind to androgen receptors in muscle tissue while having reduced affinity for prostate tissue. This creates tissue-specific quality differences in receptor binding, allowing muscle anabolism without prostate stimulation.
Solution Approach 2:
The patent employs parameter changes by systematically varying molecular parameters of the androgen modulators including substituent types (halogens, alkyl groups, heteroaryl groups), substituent positions, and molecular geometry to optimize the ratio of muscle-to-prostate receptor binding affinity. These parameter modifications enable decoupling of anabolic effects from androgenic side effects.
2Strength
If androgen agonists are used to increase muscle mass, then anabolic action is improved, but acne and other androgenic side effects occur
Solution Approach 1:
The patent applies local quality by designing compounds with selective tissue affinity profiles where the molecular structure preferentially interacts with androgen receptors in skeletal muscle while minimizing interaction with receptors in sebaceous glands and other androgen-sensitive tissues responsible for acne development.
Solution Approach 2:
The patent employs parameter changes by modifying molecular parameters such as lipophilicity, molecular size, and receptor binding pocket compatibility to achieve selective muscle tissue penetration and binding while reducing binding to other androgen-responsive tissues that would otherwise be stimulated by conventional androgens.
3Reliability
If conventional androgen therapies are used, then therapeutic benefits are achieved, but tissue-selective effects are lacking
Solution Approach 1:
The patent applies local quality by creating a series of androgen modulators with differentiated molecular characteristics that enable selective targeting of specific tissue types. The compounds in formula I exhibit varying degrees of tissue selectivity based on their substituent patterns, allowing optimization for specific therapeutic indications while maintaining reliable anabolic activity in muscle tissue.
Data Source
AI summary
This invention provides compounds of formulas I, Ia, Ib, Ic, Id, Ie, If or Ig or salts thereof, pharmaceutical compositions comprising a compound of formulas I, Ia, Ib, Ic, Id, If or Ig and a pharmaceutically acceptable excipient, methods of modulating the androgen receptor, methods of treating diseases beneficially treated by an androgen receptor modulator (e.g., sarcopenia, prostate cancer, contraception, type 2 diabetes related disorders or diseases, anemia, depression, and renal disease) and processes for making compounds of formulas I, Ia, Ib, Ic, Id, Ie, If or Ig and intermediates useful in the preparation of same.