Deuterated Rivaroxaban Derivatives for Factor Xa Inhibition
Solution Overview
Problem
Current treatments for conditions like pulmonary embolism, stroke, and thrombosis using rivaroxaban have adverse events and a need for new compounds that effectively inhibit coagulation factor Xa without pyrogenic reactions.
Innovation Solution
Development of novel substituted oxazolidinones derivatives and their pharmaceutically acceptable salts, which are used in compositions to treat diseases susceptible to factor Xa inhibition, including pulmonary embolism, stroke, and thrombosis, while also serving as reagents for rivaroxaban concentration determination and metabolic studies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If rivaroxaban is used to inhibit coagulation factor Xa, then therapeutic effect is improved, but adverse events increase
Solution Approach 1:
The patent applies parameter changes by deuterating specific hydrogen atoms in the rivaroxaban molecule with deuterium atoms. This isotopic substitution modifies the metabolic parameters of the drug, leading to altered metabolism and reduced formation of harmful metabolites while maintaining the therapeutic effect of factor Xa inhibition.
Solution Approach 2:
The patent applies local quality by selectively deuterating only specific positions in the rivaroxaban molecule (such as positions on the morpholinone ring or other specific locations) rather than the entire molecule. This localized modification targets specific metabolic pathways responsible for adverse events while preserving the overall pharmacological activity.
2Object-affected harmful factors
If new compounds are developed to reduce adverse events, then safety is improved, but complexity of drug development increases
Solution Approach 1:
The patent simplifies the drug development process by using a systematic approach to deuterium substitution at predetermined positions in the rivaroxaban molecule. This method provides a clear framework for generating safer compounds without requiring entirely new drug discovery processes, thus reducing development complexity while improving safety.
Data Source
AI summary
This invention relates to novel compounds that are substituted oxazolidinones derivatives and pharmaceutically acceptable salts thereof. More specifically, this invention relates to novel oxazolidinones compounds that are derivatives of rivaroxaban. The invention also provides pyrogen-free compositions comprising one or more compounds of the invention and a carrier, and the use of the disclosed compounds and compositions in methods of treating diseases and condition that are beneficially treated by administering a selective inhibitor of factor Xa, such as rivaroxaban.