Furoindazole GPR84 Antagonists for Selective Anti-Inflammatory Therapy
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Solution Overview
Problem
Current compounds do not effectively target GPR84 for the treatment or prophylaxis of various diseases, including autoimmune diseases, inflammatory disorders, inflammatory eye diseases, inflammatory kidney and liver diseases, lung diseases, metabolic and metabolic-endocrine disorders, and neuropathic pain disorders.
Innovation Solution
Development of furoindazole compounds that act as antagonists of the G-protein coupled receptor 84 (GPR84), addressing the expression and activity of GPR84 in various cell types to modulate inflammatory and fibrotic responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing compounds are used to target GPR84, then the treatment approach is simple, but the therapeutic effectiveness is insufficient
Solution Approach 1:
The patent applies parameter changes by systematically modifying molecular parameters of the compound structure, specifically incorporating a furoindazole core with specific substituent patterns (R1-R7 groups) to optimize GPR84 binding affinity and therapeutic effectiveness while managing structural complexity
Solution Approach 2:
The patent employs composite materials by creating compounds with a composite molecular structure consisting of a furoindazole core combined with various substituent groups (aromatic rings, heterocycles, alkyl chains), forming a composite pharmacophore that achieves enhanced therapeutic effectiveness against GPR84
2Reliability
If GPR84 is inhibited to treat inflammatory diseases, then therapeutic benefits are achieved, but the compound must have high selectivity to avoid off-target effects
Solution Approach 1:
The patent applies local quality by designing specific local structural features within the molecule, such as particular substituent configurations at specific positions (R3, R4, R5, R6 groups) that enhance selectivity for GPR84 while maintaining overall structural manageability
Solution Approach 2:
The patent employs dynamics by incorporating flexible substituents and rotatable bonds (alkyl chains, heterocyclic groups) that allow the molecule to adapt its conformation for optimal binding to GPR84, enhancing selectivity through dynamic molecular recognition
Data Source
AI summary
Furindazole compounds of general formula (I):pharmaceutical compositions and combinations comprising compounds of formula (I) and the use of compounds of formula (I) for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases.