Intestinal Uric Acid Transporter Agonists for Low-Toxicity Excretion
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Solution Overview
Problem
Current uric acid-reducing drugs cause liver and kidney damage, necessitating the development of novel compounds that enhance uric acid transport in the intestines to lower blood uric acid levels without toxic side effects.
Innovation Solution
A compound represented by formula (I) and its derivatives, which activate and enhance uric acid transport in intestinal epithelial cells, reducing blood uric acid concentration and alleviating the burden on the kidneys.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional uric acid-reducing drugs (allopurinol, febuxostat, benzbromarone) are used to lower blood uric acid levels, then uric acid reduction effect is achieved, but liver and kidney damage occurs
Solution Approach 1:
The patent shifts the site of uric acid excretion from the kidneys (single pathway) to the intestines (alternative pathway). By activating intestinal ABCG2 transporters, uric acid is excreted through feces instead of being concentrated in the kidneys, thereby segmenting the excretion pathway and protecting renal function.
Solution Approach 2:
The compound acts as an intermediary that activates ABCG2 transporters in intestinal cells. This intermediary mechanism enables uric acid to be transported from blood into intestinal lumen without directly damaging liver or kidney tissues, mediating the excretion process safely.
2Quantity of substance
If intestinal uric acid transport is enhanced to lower blood uric acid levels, then uric acid reduction effect is achieved, but drug absorption into circulatory system may cause systemic side effects
Solution Approach 1:
The compound exhibits local action primarily in intestinal epithelial cells where ABCG2 transporters are activated. The drug's effect is concentrated in the intestine rather than distributing systemically, creating local quality differentiation that reduces systemic toxicity while maintaining uric acid-lowering efficacy.
Solution Approach 2:
The compound is designed to be minimally absorbed into the circulatory system, allowing it to exert its primary effect locally in the intestine. The unabsorbed drug continues to serve its function of activating intestinal transporters, while the small amount absorbed is rapidly excreted, creating a self-limiting mechanism that prevents accumulation and systemic side effects.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compounds effectively lower blood uric acid levels, reducing toxicity to other organs and improving liver and kidney function with minimal absorption into the circulatory system.
Implementation Method 1
The compound involved in the present disclosure can activate and enhance the uric acid transport function in intestinal epithelial cells in the intestines, so that uric acid in the blood can be excreted into the digestive tract
Data Source
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AI summary
A uric acid transporter agonist compound as represented by formula (I), a pharmaceutical composition, and a preparation method therefor and the use thereof. The compound as a drug is hardly absorbed into an in-vivo circulation system, and has good uric acid transport protein agonistic activity.