EP4 Antagonist Compounds for IL-23 Mediated Immune Diseases
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Solution Overview
Problem
Current treatments for immune diseases and allergies lack effective therapeutic options with selective EP4 receptor antagonism, and existing compounds like AE3-208 either fail to show therapeutic efficacy or exacerbate conditions such as DSS-induced colitis.
Innovation Solution
Development of compounds with selective EP4 receptor antagonistic activity, specifically formulated as pharmaceutical compositions for administration to treat IL-23 mediated diseases, which inhibit IL-23 production and reduce inflammation in animal models.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing EP4 antagonist compounds (e.g., AE3-208) are used for treatment, then immune disease or allergy may be prevented or delayed, but they fail to show therapeutic efficacy or exacerbate conditions such as DSS-induced colitis
Solution Approach 1:
The patent applies parameter changes by optimizing the chemical structure of EP4 antagonist compounds. Specifically, the invention modifies molecular parameters such as substituent groups (R1-R6), ring structures (Ar1, Ar2), and linker configurations to create compounds with improved therapeutic profiles. The general formula structure allows systematic variation of chemical parameters to achieve compounds that maintain EP4 antagonism while reducing harmful effects on colitis and improving overall therapeutic efficacy.
2Adaptability or versatility
If selective EP4 receptor antagonists are developed, then therapeutic options for immune diseases are expanded, but the complexity of identifying compounds with appropriate selectivity and efficacy increases
Solution Approach 1:
The patent applies segmentation by dividing the complex task of drug development into manageable components. The invention provides a segmented molecular framework with defined core structures (Ar1, Ar2, linker) and variable substituent positions (R1-R6). This segmentation allows researchers to systematically explore structure-activity relationships by modifying individual components while maintaining the overall pharmacological profile, thereby reducing the complexity of identifying selective and effective compounds.
Solution Approach 2:
The patent employs parameter changes by establishing a systematic approach to modify molecular parameters within the general formula. By varying substituents at specific positions (R1-R6), aromatic ring structures (Ar1, Ar2), and linker types, the invention creates a library of compounds with predictable variations in selectivity and efficacy. This parameter-based approach simplifies the identification process compared to random screening.
3Reliability
If compounds with broad EP4 antagonism are used, then immune disease prevention may be achieved, but side effects and harmful factors increase
Solution Approach 1:
The patent applies local quality by optimizing specific regions of the molecule to achieve differential effects. The invention structures the compound with distinct functional zones: aromatic rings (Ar1, Ar2) for EP4 receptor binding, linker regions for structural connectivity, and substituent positions (R1-R6) for fine-tuning pharmacological properties. This local optimization allows the compound to maintain effective EP4 antagonism for disease prevention while minimizing interactions with other biological targets that would cause side effects.
Data Source
AI summary
This invention relates to a compound with EP4 antagonistic activity, or a pharmaceutically acceptable salt with EP4 receptor antagonistic activities, which is useful in the treatment of immune disease or allergy. This invention also relates to a compound of formula (I), (II), (III), (IV), (Va) or (Vb), or a pharmaceutically acceptable salt thereof with EP4 receptor antagonistic activities, which is useful in the treatment of immune disease or allergy. This invention also relates to a pharmaceutical composition for the treatment of immune disease or allergy which comprises a therapeutically effective amount of a compound of formula (I), (II), (III), (IV), (Va) or (Vb), or a pharmaceutically acceptable salt thereof. Further this invention relates to a method for the treatment of immune disease or allergy in an animal subject including a mammalian subject, which comprises administering to the animal subject including a mammalian subject a compound of the formula (I), (II), (III), (IV), (Va) or (Vb), or a pharmaceutically acceptable salt thereof.