Deuterium-Enriched Conjugates for Angiogenesis Inhibition
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current cancer treatments are limited, particularly for blood cancers like multiple myeloma, and there is a need for new methods to inhibit angiogenesis, which is associated with tumor growth and various disorders.
Innovation Solution
Development of deuterium-enriched isoindolinonyl-piperidinonyl and oxoquinazolin-3(4H)-yl-piperidinonyl conjugates that provide therapeutic agents with improved properties by enriching deuterium at the chiral center, potentially inhibiting angiogenesis and treating medical disorders such as cancer and inflammatory conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional chemotherapy is used to treat blood cancers, then treatment options are available, but treatment effectiveness is limited when conventional chemotherapy fails
Solution Approach 1:
The patent introduces deuterium substitution at the chiral center of the piperidine-2,6-dione moiety, changing the physical and chemical parameters of the compound. This isotopic substitution reduces enantiomer interconversion and provides enantiomerically pure forms, thereby improving treatment effectiveness for blood cancers that have become resistant to conventional chemotherapy
Solution Approach 2:
The patent specifically targets the chiral center at the piperidine-2,6-dione moiety, creating asymmetric structures with defined stereochemistry. By providing enantiomerically pure forms through deuterium enrichment, the invention optimizes the biological activity and therapeutic effect, addressing the limitation of conventional chemotherapy in treating resistant blood cancers
2Productivity
If tumor-induced angiogenesis is promoted, then tumor growth occurs, but this leads to undesired angiogenesis associated with various disorders
Solution Approach 1:
The patent converts the harmful process of angiogenesis into a beneficial therapeutic target. By designing compounds that specifically inhibit angiogenic pathways while maintaining necessary physiological functions, the invention addresses both tumor growth control and prevention of undesired angiogenesis in various disorders through the same mechanistic approach
3Stability of the object's composition
If deuterium enrichment is provided at the chiral center, then enantiomer interconversion is reduced and enantiomerically pure forms are obtained, but this requires specialized synthesis methods
Solution Approach 1:
The patent employs preliminary action by incorporating deuterium at the chiral center during the synthesis process itself, rather than attempting to separate enantiomers after formation. This approach of building in the desired stereochemical configuration from the start reduces enantiomer interconversion and provides enantiomerically pure forms more efficiently
Solution Approach 2:
By changing the isotopic parameter (substituting deuterium for hydrogen) at the chiral center, the patent fundamentally alters the kinetic and thermodynamic properties of the molecule. This parameter change stabilizes the enantiomeric form and reduces interconversion, achieving the desired stereochemical stability through physical-chemical modification rather than complex separation processes
Data Source
AI summary
The invention provides deuterium-enriched isoindolinonyl-piperidinonyl conjugates, deuterium-enriched oxoquinazolin-3(4H)-yl-piperidinonyl conjugates, pharmaceutical compositions, and methods of using such conjugates and pharmaceutical compositions to treat cancer, angiogenesis disorders, immune disorders, and other medical disorders.