Formula I Compounds Inhibiting ASK-1 for Liver Disease
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Solution Overview
Problem
Current treatments lack effective ASK-1 inhibitors for managing autoimmune disorders, neurodegenerative diseases, inflammatory diseases, chronic kidney disease, cardiovascular disease, metabolic disorders, and acute and chronic liver diseases, where ASK-1 plays a significant role in disease progression.
Innovation Solution
Development of specific compounds represented by Formula I, or their pharmaceutically acceptable salts or esters, which act as ASK-1 inhibitors, administered to prevent or treat ASK-1 mediated diseases by inhibiting the ASK-1 pathway.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for ASK-1 mediated diseases, then existing therapeutic options are limited, but effective disease management is not achieved
Solution Approach 1:
The patent applies parameter changes by developing novel chemical compounds with specific molecular structures (Formula I) that exhibit ASK-1 inhibitory activity. The compounds feature variable substituents (R1-R4, X1-X3) that can be modified to optimize pharmacological properties, thereby creating effective therapeutic agents where none previously existed for ASK-1 mediated diseases
2Object-affected harmful factors
If ASK-1 pathway is inhibited, then disease progression is reduced, but specific effective inhibitors were previously unavailable
Solution Approach 1:
The patent segments the ASK-1 enzyme structure into identifiable binding regions and develops compounds that specifically target these regions. The modular chemical structure (Formula I with variable R groups and X substituents) allows for targeted inhibition of ASK-1's catalytic domain, enabling effective disease progression control through selective pathway inhibition
3Reliability
If compounds of Formula I are administered, then ASK-1 activity is inhibited, but therapeutic efficacy must be optimized
Solution Approach 1:
The patent applies local quality by concentrating the ASK-1 inhibitory activity in specific molecular regions of the Formula I compounds. The core structure with strategically positioned substituents (particularly R1-R4 and X1-X3 groups) creates localized interaction zones that bind to ASK-1's active site, achieving reliable inhibition while maintaining a manageable structural framework
Data Source
AI summary
The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts and esters 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).