Quinazolinone Derivative Modulating TNF-α to Reduce Hematologic Toxicity
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Solution Overview
Problem
Lenalidomide, a drug used to regulate TNF-α activity, has significant side effects such as myelosuppression, deep vein thrombosis, and teratogenesis, limiting its effectiveness due to hematologic toxicity, necessitating the development of derivatives with improved structures.
Innovation Solution
A quinazolinone derivative is developed, which can regulate TNF-α generation or activity, offering a pharmaceutical composition for treating cancer and inflammatory diseases with potentially reduced side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Lenalidomide is used to regulate TNF-α activity, then the therapeutic effect on cancer and inflammatory diseases is improved, but significant side effects such as myelosuppression, deep vein thrombosis, and teratogenesis occur
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of Lenalidomide to create new derivatives with improved properties. Specifically, the invention introduces various substituent groups at different positions of the Lenalidomide molecular structure, thereby altering its biological activity parameters to reduce side effects while maintaining or enhancing therapeutic efficacy against cancer and inflammatory diseases
Solution Approach 2:
The patent creates composite molecular structures by combining the Lenalidomide core structure with additional functional groups and substituents. These composite derivatives integrate the beneficial TNF-α regulatory activity of Lenalidomide with modified pharmacological properties that reduce hematologic toxicity and other side effects
2Reliability
If Lenalidomide is used at effective doses, then TNF-α regulation is achieved, but hematologic toxicity limits effectiveness requiring dose reduction
Solution Approach 1:
The patent modifies the dosing parameters by creating derivatives that achieve effective TNF-α regulation at lower doses or with improved therapeutic windows. The structural modifications enable the compounds to maintain efficacy while reducing the hematologic toxicity that currently limits dose escalation in Lenalidomide treatment
Data Source
AI summary
Disclosed are a quinazolinone derivative, a preparation method therefor, a pharmaceutical composition, and applications. Provided are a compound represented by formula I, a pharmaceutically acceptable salt, a solvate, a crystal form, a eutectic crystal, a stereoisomer, an isotope compound, a metabolite, or a prodrug thereof. Generation or activity of a cell factor can be regulated, and accordingly, cancers and inflammatory diseases can be effectively treated.