Quinoline Factor XI Inhibitors With Optimized Pharmacokinetics
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Solution Overview
Problem
Existing treatments for thrombosis and related conditions, such as thromboembolic disorders, are inadequate in effectively inhibiting Factor XI activation, leading to uncontrolled blood coagulation and potential life-threatening complications.
Innovation Solution
Development of quinoline derivatives that act as selective Factor XI activation inhibitors, which can be administered alone or in combination with other therapeutics to inhibit Factor XI activation and reduce blood clot formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments are used for thrombosis, then blood coagulation control is maintained, but Factor XI activation inhibition is insufficient leading to uncontrolled coagulation
Solution Approach 1:
The patent modifies the chemical structure by introducing specific substituents (R1, R2, R3, Rx) at defined positions on the quinoline core, changing molecular parameters to achieve optimal Factor XI activation inhibition while maintaining safe pharmacokinetic profiles
Solution Approach 2:
The invention combines multiple functional groups (quinoline core, carboxylic acid, amide, heterocyclic rings) into a composite molecular structure that achieves synergistic effects for enhanced Factor XI inhibition potency and improved therapeutic properties
2Reliability
If quinoline derivatives are developed as selective Factor XI activation inhibitors, then potency in preventing thrombosis is improved, but pharmacokinetic profile optimization is required
Solution Approach 1:
The patent systematically varies molecular parameters including substituent types, positions, and configurations to optimize the balance between Factor XI inhibition potency and pharmacokinetic properties such as half-life, clearance, and bioavailability
Solution Approach 2:
The invention creates a series of derivatives with gradually modified structures to achieve dynamic optimization of pharmacokinetic parameters while maintaining therapeutic efficacy, allowing for dose and formulation adjustments
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 XI activation inhibitors.