DY40 Estrogen Receptor Antagonist Synthesis via McMurry Coupling
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Solution Overview
Problem
Current compounds used to modulate estrogen receptors (ERs) and estrogen-related receptors (ERRs) are not effective enough in treating breast cancer and other estrogen-related disorders, and there is a need for more efficient methods to synthesize these compounds for pharmaceutical use.
Innovation Solution
Development of novel compounds with specific structures that effectively antagonize ERs and ERRs, such as DY40, which has a 30-fold greater potency than 4-hydroxytamoxifen in inhibiting ERRβ and ERRγ, and a method for synthesizing these compounds using a McMurry coupling reaction, bypassing the cumbersome five-step procedure in existing methods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current compounds (e.g., 4-hydroxytamoxifen) are used to modulate ERs and ERRs, then some estrogen receptor activity is inhibited, but the potency and effectiveness are insufficient for treating breast cancer and other estrogen-related disorders
Solution Approach 1:
The patent modifies molecular parameters of existing SERM compounds by introducing specific substituents at defined positions (e.g., compound of formula I with R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12 being specific groups) to enhance binding affinity and potency against both ERs and ERRs, achieving 30-fold greater effectiveness compared to 4-hydroxytamoxifen
Solution Approach 2:
The patent creates composite molecular structures that combine features of known SERMs with additional functional groups and substituents, resulting in hybrid compounds that simultaneously target multiple estrogen-related receptors with high potency, thereby resolving the insufficiency of current single-function compounds
2Ease of manufacture
If existing five-step synthesis procedures are used to produce SERM compounds, then compounds can be manufactured, but the process is cumbersome and inefficient
Solution Approach 1:
The patent combines multiple sequential reaction steps into a single one-pot McMurry coupling reaction, merging the synthesis of the carbon-carbon double bond formation with subsequent transformations, thereby reducing the five-step procedure to one step and dramatically improving manufacturing efficiency
Solution Approach 2:
The patent performs preliminary preparation of reactants (e.g., ketone substrates with specific substituents) that can directly undergo the McMurry coupling reaction to yield the final SERM compound, eliminating the need for intermediate purification and isolation steps, thus streamlining the manufacturing process
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The novel compounds effectively modulate ERs and ERRs, providing a more potent treatment for breast cancer and other estrogen-related disorders, with DY40 demonstrating significant antagonistic activity against ERRβ and ERRγ, and the synthesis method offers a more efficient and cost-effective production process.
Implementation Method 1
a method for synthesizing these compounds using a McMurry coupling reaction
Data Source
AI summary
Disclosed are novel compositions and novel methods for the creation of both the novel compounds and known compounds. Also disclosed are methods for use of the novel compounds for treating a variety of diseases relating to decreasing or preventing activation of estrogen receptors and/or estrogen related receptors.