Selective Factor XIa Inhibitors for Thrombosis Treatment
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Solution Overview
Problem
Current methods for inhibiting blood coagulation, particularly in conditions like thrombosis and embolism, are inadequate in selectively targeting Factor XIa and plasma kallikrein, leading to potential side effects and incomplete prevention of thrombotic events.
Innovation Solution
Development of compounds of Formula I, which are selective inhibitors of Factor XIa and dual inhibitors of Factor XIa and plasma kallikrein, designed to treat or prevent thrombosis, embolism, hypercoagulability, and fibrotic changes, and can be used in combination with other therapeutic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current methods for inhibiting blood coagulation are used, then thrombotic events can be prevented, but side effects occur and prevention is incomplete due to lack of selectivity
Solution Approach 1:
The patent applies local quality by designing compounds with specific molecular structures (Formula I) that target only Factor XIa and plasma kallikrein enzymes. The compounds contain specific functional groups (amide, carboxylic acid, hydroxyl) positioned at precise locations to bind selectively to the active sites of these enzymes, thereby inhibiting thrombotic events without affecting other coagulation factors, thus reducing side effects while maintaining reliable prevention.
Solution Approach 2:
The patent employs parameter changes by modifying molecular parameters such as pH sensitivity and binding affinity. The compounds are designed to exhibit optimal inhibitory activity at physiological pH levels while maintaining selectivity for Factor XIa and plasma kallikrein. By adjusting molecular weight, hydrophobicity, and electrostatic properties, the compounds achieve enhanced specificity and reduced off-target effects compared to conventional non-selective anticoagulants.
2Object-affected harmful factors
If selective inhibitors of Factor XIa and plasma kallikrein are developed, then side effects are reduced, but the complexity of the compound structure increases
Solution Approach 1:
The patent applies segmentation by dividing the inhibitor molecule into distinct functional domains: a core structure (Formula I) that provides selectivity for Factor XIa and plasma kallikrein, and additional substituents (R1, R2, R3 groups) that can be independently optimized for pharmacokinetic properties. This modular approach allows complex selective inhibition to be achieved through systematic combination of simpler structural elements rather than requiring a single highly complex molecule.
Solution Approach 2:
The patent utilizes composite materials by combining multiple chemical moieties into a single hybrid molecule. The compounds integrate amide bonds, carboxylic acid groups, and aromatic rings in specific configurations that create a composite structure with both high selectivity for the target enzymes and improved pharmacological properties. This composite approach enables the molecule to simultaneously achieve specificity and reduced side effects.
Data Source
AI summary
The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma kallikrein.