Steroidal SARMs 13-Position Side Chains Tissue Selectivity
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Solution Overview
Problem
Current antiandrogens used to treat androgen-dependent diseases often lack sufficient affinity for the androgen receptor, possess undesirable agonistic activity, and have systemic side effects, particularly when used topically for skin-related conditions.
Innovation Solution
Development of steroidal selective androgen receptor modulators (SARMs) with specific side-chains at the 13-position that selectively block androgen receptors in certain tissues while activating them in others, minimizing systemic activity and maximizing local efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If steroidal antiandrogens are used to block androgen receptors, then receptor affinity is improved, but undesirable agonistic activity increases
Solution Approach 1:
The patent applies local quality by introducing specific side-chains at the 13-position of the steroidal nucleus that create tissue-selective effects. Different side-chain configurations (such as 13β-alkyl or 13α-alkyl groups) provide different spatial and electronic properties that enable the compound to act as an antagonist in some tissues while minimizing agonistic activity in others, thus resolving the contradiction between high receptor affinity and undesirable agonistic effects
Solution Approach 2:
The patent employs parameter changes by systematically varying the side-chain structure at the 13-position (including different alkyl groups, their stereochemistry, and positioning) to optimize the balance between antagonist potency and agonistic activity. By changing these molecular parameters, the invention achieves compounds with high receptor affinity that lack the problematic agonistic characteristics of conventional steroidal antiandrogens
2Object-generated harmful factors
If non-steroidal antiandrogens are used to avoid agonistic activity, then harmful factors are reduced, but receptor affinity deteriorates
Solution Approach 1:
The patent creates a composite molecular structure that combines the advantages of both steroidal and non-steroidal compounds. The core steroidal nucleus provides high receptor affinity similar to natural androgens, while the modified side-chains at the 13-position introduce properties that reduce agonistic activity. This composite approach yields a molecule that achieves both high affinity and reduced harmful effects, overcoming the limitations of purely non-steroidal antiandrogens
3Ease of operation
If antiandrogens are applied topically for skin conditions, then local efficacy is improved, but systemic side effects increase
Solution Approach 1:
The patent applies local quality through the design of tissue-selective side-chains that enhance affinity for androgen receptors in skin tissues while having reduced interaction with receptors in other organs. This molecular-level local quality allows the compound to exert its antiandrogenic effect primarily at the application site, minimizing systemic absorption and distant side effects when used topically
Data Source
AI summary
Compounds having the structure or their salts:are used to treat or reduce le likelihood of acquiring androgen-dependent diseases, such as prostate cancer, benign prostatic hyperplasia, polycystic ovarian syndrome, acne, hirsutism, seborrhea, androgenic alopecia and male baldness. They can be formulated together with pharmaceutically acceptable diluent or carrier or otherwise made into any pharmaceutical dosage form. Some of these compounds having tissue-specific antiandrogenic activity and tissue-specific androgenic activity can be used to treat or reduce the risk of developing diseases related to loss of androgenic stimulation. Combinations with other active pharmaceutical agents are also disclosed.