Pyridine Derivatives as Selective S1P1 Agonists for Immunomodulation
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Solution Overview
Problem
Current immunosuppressive therapies for managing uncontrolled inflammatory diseases and organ rejection in transplantation are associated with significant side effects and compromised immune defense, requiring the development of more targeted and less toxic immunomodulating agents.
Innovation Solution
Development of S1P1/EDG1 receptor agonists, specifically pyridine derivatives with reduced activity on the S1P3 receptor, which effectively reduce circulating and infiltrating lymphocytes without affecting their maturation or expansion, thereby improving vascular function and offering a new immunomodulating therapy with reduced infection risk and end-organ damage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If broad immunosuppressive therapies are used to treat uncontrolled inflammatory diseases and prevent organ rejection, then the immunomodulating effect is improved, but the body's defense against infection and malignancies is compromised and side effects increase
Solution Approach 1:
The patent segments the immune system's regulatory mechanisms by specifically targeting the S1P1 receptor pathway. Instead of using broad immunosuppressants that affect multiple immune pathways, the invention uses selective S1P1 receptor agonists that modulate only the specific pathway responsible for lymphocyte circulation and infiltration, thereby achieving immunomodulation without compromising overall immune defense.
Solution Approach 2:
The patent introduces S1P1 receptor agonists as intermediary compounds that mediate the immunomodulating effect. These compounds act as selective mediators between the therapeutic goal (reducing inflammation and preventing rejection) and the immune system, achieving the desired effect through a specific molecular pathway without the need for broad-spectrum immunosuppression.
2Reliability
If standard immunosuppressive drugs are used at high dosages to maximize protection against rejection, then the immunomodulating effect is improved, but organ damage is accelerated and side effects increase
Solution Approach 1:
The patent changes the key parameter of receptor selectivity by designing compounds with high specificity for the S1P1 receptor. This parameter change allows achieving effective immunomodulation at lower dosages, thereby avoiding the organ damage and side effects associated with high-dosage conventional immunosuppressants while maintaining protection against rejection.
3Object-affected harmful factors
If current immunosuppressive therapies are used to suppress the immune system, then the inflammatory response is reduced, but the body's ability to react to infections is severely compromised
Solution Approach 1:
The patent segments the immune response by selectively modulating the S1P1 receptor pathway that controls lymphocyte circulation and tissue infiltration. This segmentation allows reducing harmful inflammatory responses while preserving other essential immune functions such as the body's ability to react to infections, thereby achieving targeted immunomodulation without broad immunosuppression.
Data Source
AI summary
The invention relates to compounds of the Formula (I), Formula (I) wherein R1 and R2 are as described in the description, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunomodulating agents.