Adenosine A3 Receptor Antagonist for Liver Disease Selectivity
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Solution Overview
Problem
Current adenosine derivatives lack selectivity for specific tissue types due to widespread distribution of adenosine receptors, limiting their therapeutic application, and there is a need for effective adenosine A3 receptor antagonists for treating nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), liver fibrosis, and liver cirrhosis.
Innovation Solution
A novel adenosine derivative compound acting as an adenosine A3 receptor antagonist, represented by a specific chemical formula, is synthesized and formulated into a pharmaceutical composition for oral administration, using a vehicle that includes methyl cellulose, dimethyl sulfoxide, and polyethylene glycol, to target liver diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If adenosine derivatives are used to treat liver diseases, then therapeutic effects are achieved, but selectivity for specific tissue types is insufficient due to widespread distribution of adenosine receptors
Solution Approach 1:
The patent applies local quality by designing adenosine derivatives with specific molecular structures (substituted purine or pyrimidine rings with particular functional groups) that confer selectivity for adenosine A3 receptors in liver tissue. This structural modification enables the drug to preferentially interact with liver-specific receptor variants while minimizing effects on other tissue types, thus achieving both therapeutic efficacy and tissue selectivity
2Reliability
If adenosine A3 receptor antagonists are developed for liver diseases, then disease alleviation is achieved, but compound selectivity and affinity remain insufficient
Solution Approach 1:
The patent employs parameter changes by systematically modifying molecular parameters of adenosine derivatives, including substituent types (halogen, alkyl, aryl groups), positions of substitution on the purine/pyrimidine ring, and stereochemical configurations. These parameter variations are optimized to enhance binding affinity for adenosine A3 receptors while improving selectivity over other adenosine receptor subtypes, thereby achieving both disease alleviation and precise receptor targeting
Data Source
AI summary
A pharmaceutical composition for preventing or treating liver disease is provided. The pharmaceutical composition comprising a compound represented by formula 1 below or a pharmaceutically acceptable salt of the compound as an active ingredient:where A is S, R is a linear or branched C1-C5 alkyl which is non-substituted or is independently or selectively substituted with one or more C6-C10 aryl groups, a benzyl which is non-substituted or is independently or selectively substituted with halogen or one or more linear or branched C1-C4 alkoxy groups, or a hydroxycarbonyl-substituted benzyl, and Y is H or a halogen atom.