Substituted Oxopyridine Derivatives for Factor XIa Inhibition
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Solution Overview
Problem
Existing anticoagulants for treating thrombotic or thromboembolic disorders have limitations such as short half-life, bleeding risks, narrow therapeutic windows, and unsatisfactory prophylaxis, and there is a need for compounds with improved pharmacokinetic behavior and broader therapeutic efficacy.
Innovation Solution
Development of substituted oxopyridine derivatives that act as potent factor XIa inhibitors, providing enhanced pharmacokinetic behavior and a wider therapeutic window.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If traditional anticoagulants are used, then thrombotic disorders can be treated, but the half-life is short and bleeding risks increase
Solution Approach 1:
The patent modifies the molecular structure of oxopyridine derivatives by changing chemical parameters (substituents at specific positions) to achieve optimal pharmacokinetic properties. This includes adjusting lipophilicity, metabolic stability, and binding affinity to factor XIa, thereby extending half-life while maintaining safety profile.
Solution Approach 2:
The invention creates composite molecular structures by combining the core oxopyridine scaffold with various functional groups and substituents (e.g., aromatic rings, heterocycles, alkyl chains). This composite approach allows optimization of multiple properties simultaneously: binding affinity, metabolic stability, and pharmacokinetic behavior.
2Reliability
If existing anticoagulants are administered, then thrombus formation is inhibited, but the therapeutic window is narrow
Solution Approach 1:
The patent introduces specific local modifications at defined positions of the oxopyridine molecule (e.g., positions 2, 4, 5, 6) to create sterics that selectively enhance binding to factor XIa while avoiding off-target effects. This localized structural optimization creates a wider therapeutic window by reducing non-specific interactions.
Solution Approach 2:
The invention creates analogs and derivatives of the parent oxopyridine structure by copying the core pharmacophore and systematically varying substituents. This allows identification of optimal structures that maintain high efficacy while improving safety margins through structure-activity relationship analysis.
3Reliability
If factor XIa inhibitors are developed, then coagulation cascade is blocked, but pharmacokinetic behavior needs improvement
Solution Approach 1:
The patent incorporates prodrugs or metabolically stable structures that resist rapid degradation, ensuring the compound remains active in the circulation longer. This preliminary design consideration addresses pharmacokinetic issues before clinical administration, extending the duration of action and improving dosing frequency.
Data Source
AI summary
The invention relates to substituted oxopyridine derivatives and to processes for their preparation, and also to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular cardiovascular disorders, preferably thrombotic or thromboembolic disorders, and oedemas, and also ophthalmic disorders.