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, capable of being used alone or in combination with other therapeutic agents to treat thrombotic conditions, including thrombosis, embolism, and hypercoagulability.
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 due to lack of selective targeting
Solution Approach 1:
The patent segments the blood coagulation inhibition function into two distinct selective targets: Factor XIa and plasma kallikrein. By designing compounds that specifically inhibit these two proteases while sparing other coagulation factors, the invention achieves reliable thrombotic event prevention without the broad-spectrum side effects of non-selective anticoagulants.
Solution Approach 2:
The patent applies local quality by creating compounds with specific molecular structures (Formula I and Formula II) that are tailored to bind selectively to Factor XIa and plasma kallikrein active sites. This localized specificity ensures inhibition occurs only at the intended targets, preventing off-target effects while maintaining effective thrombosis prevention.
2Object-affected harmful factors
If selective inhibitors of Factor XIa and plasma kallikrein are developed, then side effects are minimized, but the complexity of the compound structure increases
Solution Approach 1:
The patent employs parameter changes by systematically modifying molecular parameters in Formula I and Formula II compounds, including substituent groups (R1, R2, R3, R4), ring structures, and stereochemical configurations. These parameter variations allow optimization of selectivity for Factor XIa and plasma kallikrein while managing structural complexity through defined chemical space exploration.
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.