Substituted Triazolones Inhibit PREP for COPD Inflammation
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Solution Overview
Problem
Current treatments for chronic obstructive pulmonary disease (COPD) primarily focus on symptom management and are limited in addressing the underlying inflammatory processes, with no effective means to reduce prolyl endopeptidase (PREP)-dependent PGP production, which contributes to neutrophil recruitment and inflammation.
Innovation Solution
Development of novel substituted 2,4-dihydro-3H-1,2,4-triazol-3-ones that act as potent inhibitors of prolyl endopeptidase (PREP), reducing PGP production and subsequent neutrophil recruitment, especially in the lungs, thereby addressing acute and chronic inflammatory processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If conventional immunomodulatory treatments are used to reduce inflammation, then inflammatory processes are suppressed, but side effects increase
Solution Approach 1:
The patent applies parameter changes by developing PREP inhibitors with specific molecular structures (substituted triazolones) that selectively target the PREP enzyme's active site. By modifying chemical parameters (molecular structure, substitution patterns) of the inhibitor compounds, the patent achieves selective inhibition of PREP-dependent PGP production while minimizing non-specific immunosuppression and associated side effects
Solution Approach 2:
The patent uses PREP inhibitors as intermediary substances that specifically block the conversion of collagen fragments to PGP by PREP enzyme. This intermediary action prevents PGP formation (the harmful mediator of neutrophil recruitment) without directly suppressing the entire immune system, thereby reducing inflammation while avoiding broad immunosuppressive side effects
2Ease of operation
If symptom management treatments are used for COPD, then symptoms are relieved, but underlying inflammatory processes are not addressed
Solution Approach 1:
The patent extracts and specifically targets the underlying pathological mechanism (PREP-dependent PGP production) separate from the symptoms. By developing compounds that specifically inhibit PREP enzyme activity, the patent addresses the root cause (excessive PGP production driving neutrophil recruitment) rather than merely managing symptoms, while the selective mechanism ensures targeted action on the inflammatory pathway
Solution Approach 2:
The patent applies preliminary action by preventing PGP formation before it can recruit neutrophils and initiate inflammatory cascades. The PREP inhibitors block the enzymatic conversion of collagen fragments to PGP upstream in the pathological pathway, preventing the subsequent neutrophil recruitment and inflammation before they occur
Data Source
AI summary
The invention relates to prolyl endopeptidase (PREP) inhibitors of formula (I) which contain a condensed 2,4-dihydro-3H-1,2,4-triazol-3-one ring system, methods for producing same, the use thereof alone or in combinations for treating and/or preventing diseases, and the use thereof for producing drugs for treating and/or preventing diseases, in particular for treating and/or preventing inflammatory lung diseases (COPD).