Domide Molecular Glue Derivatives for Low-Toxicity Tumor Targeting
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Solution Overview
Problem
Existing domide compounds used for immunomodulation and antitumor therapy suffer from high toxicity and undesirable efficacy, particularly when targeting tumors with low receptor expression.
Innovation Solution
Development of a domide molecular glue derivative with a specific structure represented by formula (I) and its variants, which enhances anti-tumor activity and safety by targeting specific proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing domide compounds are used for antitumor therapy, then therapeutic effects are achieved, but high toxicity and undesirable efficacy occur
Solution Approach 1:
The patent applies parameter changes by systematically modifying the chemical structure of domide compounds through varying substituents at specific positions (R1-R7, L1-L2, X1-X3, U) to optimize the balance between therapeutic efficacy and toxicity. This involves changing molecular parameters such as substituent types, positions, and configurations to achieve desired biological activity while reducing harmful effects.
Solution Approach 2:
The patent employs composite material principles by creating complex molecular structures that combine multiple functional groups and substituents in specific configurations. The compound represents a composite molecular architecture integrating various chemical moieties (aromatic rings, heterocyclic groups, linking structures) to achieve synergistic therapeutic effects while minimizing toxicity.
2Reliability
If existing domide compounds are used, then general anti-tumor activity is achieved, but insufficient activity against tumors with low receptor expression
Solution Approach 1:
The patent applies local quality by introducing specific substituents at particular positions within the molecular structure to enhance localized interactions with target proteins. The strategic placement of electron-withdrawing or electron-donating groups, aromatic substituents, and heterocyclic moieties at specific positions (such as R2, R6, R7, L1, L2) creates localized regions of enhanced binding affinity and selectivity for target proteins with low receptor expression.
Solution Approach 2:
The patent utilizes parameter changes by systematically varying molecular properties including substituent electronegativity, steric bulk, hydrogen bonding capability, and aromaticity to optimize binding affinity for target proteins. This involves adjusting parameters such as the nature of substituents at R1-R7 positions, the structure of linking groups L1-L2, and the configuration at chiral centers to enhance activity against tumors with low receptor expression.
Data Source
AI summary
Provided are a molecular glue derivative or a tautomer, mesomer, racemate, enantiomer and diastereomer thereof, a pharmaceutically acceptable salt, hydrate and solvate thereof, a use thereof, and a preparation method therefor.