Fluorinated Estrogen Receptor Modulators for Resistance
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Solution Overview
Problem
Current treatments for estrogen-related diseases and conditions, such as breast cancer and osteoporosis, often face challenges with resistance and limited efficacy, particularly in metastatic cases and hormone-refractory cancers, where estrogen receptor signaling remains a crucial factor for tumor growth and survival.
Innovation Solution
Development of compounds that act as estrogen receptor modulators or degraders, specifically targeting ER-α, to reduce estrogen receptor activity, offering improved therapeutic activity with complete or longer-lasting tumor regression, reduced resistance development, and decreased tumor invasiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for estrogen-related diseases are used, then treatment can be provided, but resistance develops and efficacy is limited
Solution Approach 1:
The patent employs parameter changes by modifying the chemical structure of estrogen receptor modulators through fluorine substitution at specific positions (C2, C4, or C7 of the A-ring). This structural parameter change creates novel compounds with altered binding characteristics to the estrogen receptor, thereby improving treatment efficacy while reducing the development of resistance compared to existing therapies.
2Reliability
If estrogen receptor modulators are used to treat metastatic cases and hormone-refractory cancers, then tumor growth control is achieved, but treatment resistance limits complete regression
Solution Approach 1:
The patent applies parameter changes by introducing fluorine atoms at specific positions (C2, C4, or C7) of the steroid A-ring in estrogen receptor modulators. This chemical parameter modification enhances the compound's ability to induce sustained estrogen receptor downregulation and degradation, leading to complete or longer-lasting tumor regression in metastatic and hormone-refractory cancer cases.
3Ease of operation
If existing estrogen receptor therapies are administered, then symptom management is provided, but tissue-selective pharmacological activity is insufficient
Solution Approach 1:
The patent implements local quality by designing fluorinated estrogen receptor modulators with specific fluorine substitution patterns at different positions (C2, C4, or C7) of the A-ring. This localized structural modification confers tissue-selective pharmacological properties, allowing the compounds to exhibit ER antagonist activity in breast cells with minimal agonist activity in other tissues, thereby improving precision in symptom management for estrogen-sensitive diseases.
Data Source
AI summary
Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.