2H-Chromene S1P1 Agonists for Selective Lymphocyte Sequestration
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Solution Overview
Problem
Current S1P1 agonists for treating diseases induced by lymphocyte infiltration or abnormal cell proliferation often cause undesirable side effects such as infrequent pulse and reduced lung function, necessitating the development of a novel and stable S1P1 agonist with enhanced lymphocyte sequestering action without these adverse effects.
Innovation Solution
A 2H-chromene compound with a specific chemical structure, represented by formula (I), acts as an S1P1 agonist, effectively preventing or treating diseases like autoimmune diseases, inflammatory diseases, and cancer by selectively targeting lymphocyte infiltration without causing infrequent pulse or reduced lung function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If FTY720 phosphate is used as an S1P1 agonist to treat diseases induced by lymphocyte infiltration, then lymphocyte sequestration is enhanced, but infrequent pulse and reduced lung function occur as side effects
Solution Approach 1:
The patent applies local quality by designing a compound with specific structural features (2H-chromene core with particular substituent patterns) that enable selective interaction with S1P1 receptor while avoiding activation of S1P3 and S1P5 receptors. This localized molecular design achieves differential receptor engagement, providing therapeutic efficacy through S1P1 agonism while eliminating cardiotoxic and pulmonary side effects associated with non-selective agonism.
Solution Approach 2:
The patent employs parameter changes by systematically modifying molecular parameters (substituent types, positions, and configurations on the chromene core) to optimize receptor selectivity. By adjusting these chemical parameters, the compound achieves enhanced S1P1 agonist activity with improved selectivity profile, thereby maintaining lymphocyte sequestration efficacy while reducing adverse effects on heart and lung function.
2Productivity
If conventional S1P1 agonists are administered to achieve therapeutic effects, then disease symptoms are improved, but undesirable side effects limit their clinical utility
Solution Approach 1:
The patent applies segmentation by dividing the pharmacological activity into distinct receptor-specific components. The compound is designed to segment its agonist activity specifically toward S1P1 receptor, while deliberately excluding activation of S1P3 and S1P5 receptors. This segmented receptor engagement pattern allows independent optimization of therapeutic effects without being constrained by systemic side effects.
Solution Approach 2:
The patent converts the potential harm of non-selective receptor activation into benefit by designing a compound that selectively targets only the desired receptor subtype. The structural features are specifically engineered to exploit the unique binding characteristics of S1P1 receptor, transforming what would be a non-selective toxic effect into a selective therapeutic action that spares other physiological systems.
Data Source
AI summary
[Object] Provided is a compound which has an excellent S1P1 agonist action, and is useful particularly as an active ingredient for an agent for preventing and/or treating a disease induced by undesirable lymphocyte infiltration or a disease induced by abnormal proliferation or accumulation of cells. [Means for Solution] According to the present invention, a 2H-chromene compound or a derivative thereof which has an excellent S1P1 agonist action, and is useful particularly as an active ingredient of an agent for preventing and/or treating a disease induced by undesirable lymphocyte infiltration or a disease induced by abnormal proliferation or accumulation of cells can be provided. The 2H-chromene compound and a derivative thereof which are the compounds of the present invention have an S1P1 agonist action, and can be used particularly for prevention and/or treatment of a disease induced by undesirable lymphocyte infiltration or a disease induced by abnormal proliferation or accumulation of cells.