Selective Factor XI Activation Inhibitors for Thrombosis Control
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing treatments for thrombosis and related conditions, such as thromboembolic disorders, are inadequate in inhibiting Factor XI activation, which is a critical step in the blood coagulation process, leading to potentially life-threatening conditions like heart attacks and strokes.
Innovation Solution
Development of selective Factor XI activation inhibitors, represented by compounds of Formula I, 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 current therapy options are available, but Factor XI activation is not adequately inhibited
Solution Approach 1:
The patent modifies the molecular structure of Factor XI inhibitors by changing chemical parameters (substituents at positions R1-R6 in Formula I) to achieve optimal inhibition of Factor XI activation while maintaining safety profile. This structural parameter optimization enables adequate inhibition of the critical coagulation step without excessive bleeding risk.
Solution Approach 2:
The patent replaces existing mechanical or non-specific inhibition approaches with a specific molecular mechanism targeting the activation site of Factor XI. The compounds of Formula I specifically bind to and inhibit the proteolytic activity of Factor XIa, providing precise control over the coagulation cascade at the critical Factor XI activation step.
2Object-affected harmful factors
If Factor XI activation is strongly inhibited, then thrombosis risk is reduced, but bleeding risk may increase
Solution Approach 1:
The patent optimizes the balance between thrombosis inhibition and bleeding risk by carefully selecting and modifying chemical parameters of the inhibitor compounds. The substituents at positions R1-R6 are designed to achieve sufficient Factor XI activation inhibition while maintaining an acceptable safety profile, thus resolving the contradiction between efficacy and safety.
Solution Approach 2:
The patent employs partial inhibition of Factor XI activation rather than complete inhibition. The compounds provide sufficient inhibition to prevent thrombosis while allowing enough residual activity to maintain hemostasis, avoiding excessive bleeding risk. This partial action approach resolves the contradiction by achieving therapeutic effect without overwhelming side effects.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compounds effectively inhibit Factor XI activation, reducing the risk of thrombosis and associated conditions, offering improved pharmacokinetic profiles and efficacy compared to existing treatments.
Implementation Method 1
Factor XI undergoes proteolysis to afford its activated form, factor XIa, which functions as a plasma serine protease involved in the regulation of blood coagulation
Implementation Method 2
thrombosis is the formation or presence of a blood clot inside a blood vessel or cavity of the heart
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.