Selective Androgen Receptor Modulators Tissue Selectivity
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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 androgenic benefits.
Innovation Solution
Development of specific compounds, such as those described by formula I, which modulate the androgen receptor with minimal prostate stimulation, formulated as pharmaceutical compositions for administration to treat various conditions associated with insufficient androgen levels, including osteoporosis, cancer cachexia, and prostate cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If traditional androgen therapies are used to treat conditions associated with insufficient androgen levels, then muscle mass and bone density are improved, but prostate stimulation and acne occur as harmful side effects
Solution Approach 1:
The patent applies the local quality principle by designing SARM compounds with specific molecular structures (formula I with various substituent patterns) that confer tissue-selective androgen receptor modulation. Different compounds in the series show preferential binding affinity to androgen receptors in muscle and bone tissues versus prostate tissue, allowing localized therapeutic effects while minimizing unwanted prostate stimulation and acne
2Strength
If traditional androgen therapies are used to increase muscle mass, then bone density is improved, but prostate enlargement occurs as a harmful side effect
Solution Approach 1:
The SARM compounds described in the patent exhibit local quality by demonstrating tissue-selective activity through their molecular structure. The compounds preferentially activate androgen receptors in bone and muscle tissues while showing reduced affinity for prostate androgen receptors, thereby achieving bone density improvement without the prostate enlargement typically associated with traditional androgen therapies
3Quantity of substance
If androgen agonists are used to treat wasting syndromes, then muscle mass is increased, but fat mass reduction is not achieved and insulin sensitivity does not improve
Solution Approach 1:
The patent applies parameter changes by modifying the molecular parameters of androgen receptor modulators to create SARM compounds with enhanced metabolic profiles. The structural modifications (various substituent patterns on the core structure) result in compounds that not only increase muscle mass but also promote fat mass reduction and improve insulin sensitivity, providing multiple metabolic benefits simultaneously
Data Source
AI summary
This invention provides compounds of formula I, pharmaceutical compositions comprising a compound of formula I 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 and intermediates useful in the preparation of same.