ASK-1 Inhibitor Compounds for Multi-Disease Therapeutic Targeting
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Solution Overview
Problem
There is a need for the development of ASK-1 inhibitors to treat and prevent autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease, and acute and chronic liver diseases.
Innovation Solution
Development of compounds and pharmaceutical compositions that inhibit ASK-1, including specific compounds represented by Formula (I) and its derivatives, which can be administered to treat or prevent ASK-1 mediated diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ASK-1 inhibitors are developed to treat autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease, and liver diseases, then therapeutic effectiveness is improved, but drug development complexity and time increase
Solution Approach 1:
The patent segments the ASK-1 inhibitor development into distinct chemical series and structural motifs (e.g., compounds of Formula I with specific R1-R6 substituents, compounds of Formula II with triazole/imidazole rings). This segmentation allows systematic optimization of therapeutic effectiveness for different diseases while managing development complexity through modular structure-activity relationship studies.
Solution Approach 2:
The patent employs parameter changes by systematically varying chemical structures (R1, R2, R3, R4, R5, R6 substituents; triazole vs. imidazole rings; different core scaffolds) to optimize ASK-1 inhibition potency and selectivity. This enables tailored development for specific diseases while maintaining a unified inhibitor platform, balancing therapeutic effectiveness with manageable development complexity.
2Adaptability or versatility
If multiple disease indications are targeted with ASK-1 inhibitors, then versatility of treatment is improved, but clinical trial requirements and regulatory approval difficulty increase
Solution Approach 1:
The patent establishes ASK-1 inhibitors with broad universality by demonstrating efficacy across multiple disease indications including autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease, and liver diseases. This multi-functional approach allows a single inhibitor platform to address diverse diseases through ASK-1 pathway inhibition, improving versatility while potentially streamlining regulatory approval through shared mechanistic data.
Data Source
AI summary
The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, ester, stereoisomer, tautomer, solvate, hydrate, or combination thereof:which inhibit the Apoptosis signal-regulating kinase 1 (ASK-1), which associated with autoimmune disorders, neurodegenerative disorders, inflammatory diseases, chronic kidney disease, cardiovascular disease. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from ASK-1 related disease. The invention also relates to methods of treating an ASK-1 related disease in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention specifically relates to methods of treating ASK-1 associated with hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD) and non-alcohol steatohepatitis disease (NASH).