Sulfur-Substituted Glutarimide Compounds With Lower Tumor Therapy Toxicity
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Solution Overview
Problem
Existing immunomodulatory drugs for treating multiple myeloma, such as thalidomide and its derivatives, have limited efficacy and side effects, necessitating the development of new compounds with improved biological activity.
Innovation Solution
Development of sulfur-containing glutarimide-based compounds with specific structural variations, including different ring atoms and substituent groups, to enhance therapeutic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If thalidomide and its derivatives are used to treat multiple myeloma, then immunomodulatory function and anti-tumor activity are improved, but toxicity and side effects increase
Solution Approach 1:
The patent applies local quality by introducing sulfur-containing groups at specific positions of the glutarimide ring structure. The sulfur substituent is placed at the R position (position 3 of the glutarimide ring), creating localized chemical modification that enhances biological activity while controlling toxicity. This localized substitution allows the molecule to maintain its immunomodulatory function through the intact glutarimide core while the sulfur group provides enhanced anti-tumor activity with reduced side effects compared to thalidomide.
Solution Approach 2:
The patent employs parameter changes by systematically varying the sulfur-containing substituents at different positions and with different chain lengths. The general formula covers variations where R can be -SH, -S-alkyl, -S(O)-, or -S(O)2-, with alkyl groups of varying lengths (L). These parameter changes allow optimization of the balance between immunomodulatory activity and toxicity, creating a series of compounds with progressively improved therapeutic indices.
2Reliability
If thalidomide derivatives are synthesized to improve anti-cancer activity, then biological activity increases, but structural complexity increases
Solution Approach 1:
The patent applies universality by designing a general chemical formula that encompasses multiple sulfur-containing glutarimide derivatives. The core glutarimide structure with position-specific sulfur substitution serves as a universal scaffold that can accommodate various R groups and L chain lengths. This universal structure maintains the essential immunomodulatory function while allowing systematic exploration of structure-activity relationships, avoiding the need for completely separate synthesis pathways for each derivative.
Data Source
AI summary
The present disclosure relates to a compound of Formula (I) or a salt, a solvate, an isotopically enriched analog, a tautomer, a polymorph, a stereoisomer thereof, or a mixture of stereoisomers thereof, and their use for treating a tumor. The present disclosure also relates to a compound of Formula (I′) or a pharmaceutically acceptable salt, a solvate, an isotopically enriched analog, a tautomer, a polymorph, a stereoisomer thereof, or a mixture of stereoisomers thereof, and their use for treating a tumor.