2-aminoethoxyacetic acid derivatives selective factor Xa inhibition
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Solution Overview
Problem
Current anticoagulants for treating thromboembolic disorders, such as heparin and vitamin K antagonists, have limitations including nonselective action, short half-life, and high risk of bleeding, making them inefficient and unsatisfactory for effective treatment and prophylaxis.
Innovation Solution
Development of novel 2-aminoethoxyacetic acid derivatives that act as selective inhibitors of blood coagulation factor Xa, offering improved solubility in water and physiological media, which are used to prepare medicaments for treating and preventing thromboembolic disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If heparin is used as an anticoagulant, then blood coagulation is inhibited, but the action is nonselective and the risk of bleeding is high
Solution Approach 1:
The patent applies local quality by designing compounds that selectively inhibit factor Xa at a specific location in the coagulation cascade, rather than nonselectively inhibiting multiple factors like heparin. This localized inhibition at factor Xa reduces harmful effects on other coagulation factors while maintaining anticoagulant efficacy.
Solution Approach 2:
The invention segments the coagulation cascade inhibition by targeting only factor Xa rather than multiple factors simultaneously. This segmentation allows selective action at a specific point in the cascade, reducing overall bleeding risk while maintaining therapeutic effect.
2Reliability
If vitamin K antagonists are used, then factor synthesis is inhibited, but the onset of action is slow with a latency of 36 to 48 hours
Solution Approach 1:
The patent employs preliminary action by using factor Xa inhibitors that can be administered orally and take effect rapidly, eliminating the need to wait 36-48 hours for vitamin K antagonists to show effect. The inhibitor is already in active form, requiring no synthesis time.
Solution Approach 2:
The invention replaces the biological synthesis inhibition mechanism of vitamin K antagonists with a direct pharmacological inhibition mechanism. Instead of waiting for reduced factor synthesis to manifest, the compound directly inhibits active factor Xa, substituting a slower biological process with an immediate pharmacological action.
3Reliability
If heparin is administered parenterally, then anticoagulation is achieved, but the half-life is relatively short
Solution Approach 1:
The patent applies parameter changes by modifying the pharmacokinetic parameters of the anticoagulant. The factor Xa inhibitor compounds are designed with molecular structures that provide extended half-life compared to heparin, allowing for longer duration of action while maintaining effective anticoagulation.
4Reliability
If nonselective anticoagulants are used, then multiple coagulation factors are inhibited, but the action is nonselective and therapeutic index is narrow
Solution Approach 1:
The invention implements local quality by creating selectivity in the coagulation cascade inhibition. The compounds are designed to specifically target factor Xa, providing localized inhibition at this critical point rather than nonselective inhibition of multiple factors, thereby improving therapeutic index.
Solution Approach 2:
The patent segments the coagulation inhibition by isolating factor Xa as the specific target rather than inhibiting multiple factors simultaneously. This segmentation provides selective action that improves the therapeutic index by avoiding off-target effects.
Data Source
AI summary
The present application relates to novel 2-aminoethoxyacetic acid derivatives, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and also to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular thromboembolic disorders.