Heterocyclic Plasminogen Modulators for Extended Stroke Thrombolysis
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Solution Overview
Problem
Current treatments for ischemic stroke, such as intravenous tissue plasminogen activator (t-PA) and recombinant tissue plasminogen activator (rt-PA), have a short therapeutic window and risk of intracerebral hemorrhage, with recanalization rates below 25% for acute large vessel occlusion.
Innovation Solution
Development of heterocyclic compounds with plasminogen regulatory activity that promote thrombolysis and anti-inflammatory effects, offering a new mechanism for treating thromboembolic diseases like ischemic stroke, with improved therapeutic time windows and reduced bleeding risks.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If intravenous tissue plasminogen activator (t-PA) is used for ischemic stroke treatment, then recanalization can be achieved, but the therapeutic window is short and the risk of intracerebral hemorrhage increases
Solution Approach 1:
The patent introduces SMTP series compounds as intermediary substances that indirectly promote thrombolysis by modulating plasminogen conformation and enhancing t-PA activity, rather than using t-PA directly. This mediator approach allows for prolonged therapeutic effect and reduced bleeding risk compared to direct t-PA administration
Solution Approach 2:
The invention changes the biochemical parameters of the thrombolytic system by introducing compounds that alter plasminogen conformation and enhance its activation. This parameter change approach extends the therapeutic window from hours to days while maintaining efficacy and reducing hemorrhage risk
2Speed
If traditional thrombolytic agents are used, then plasminogen activation can be accelerated, but the risk of intracerebral hemorrhage increases
Solution Approach 1:
The patent converts the potential harm of excessive plasminogen activation into benefit by using SMTP compounds that mildly enhance activation through conformational modulation. This approach maintains the beneficial thrombolytic effect while avoiding the harmful hemorrhage risk associated with aggressive activation methods
Solution Approach 2:
Instead of fully activating plasminogen with strong thrombolytic agents, the invention uses partial action through SMTP compounds that enhance activation to an optimal level. This partial activation achieves sufficient thrombolysis without exceeding the safe threshold that would cause hemorrhage
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 heterocyclic compounds enhance thrombolysis promotion and provide anti-inflammatory benefits, potentially extending the therapeutic window and reducing the risk of bleeding, providing a safer and more effective treatment for ischemic stroke.
Implementation Method 1
accelerate plasminogen activation mediated by urokinase-type plasminogen activator (u-PA) or t-PA, rapidly elevate plasmin levels and promote thrombolysis by plasmin
Implementation Method 2
In addition to the plasminogen conformational regulatory function, SMTP series compounds have soluble epoxide hydrolase (sEH) inhibitory activity independent of their thrombolytic activity
Data Source
AI summary
The present invention relates to a heterocyclic compound, a pharmaceutical composition comprising same, and a preparation method for the heterocyclic compound, and further relates to a use of the compound in the preparation of a drug for treating thromboembolic diseases.