Xanthine Derivative DPP-IV Inhibitor Bioavailability
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Solution Overview
Problem
Current DPP-IV inhibitors, such as linagliptin, have limited bioavailability and side effects, necessitating the development of a compound with improved safety, higher activity, and better bioavailability for treating diabetes and related conditions.
Innovation Solution
A xanthine derivative with specific structural modifications is developed, which acts as a DPP-IV inhibitor, offering enhanced activity and reduced toxicity, particularly in the form of pharmaceutical compositions like tablets and capsules, to effectively treat diabetes and related metabolic disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If linagliptin is used as a DPP-IV inhibitor, then liver and kidney toxicity is reduced, but bioavailability remains low (F=18.4% in mice, F=30% in humans)
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of linagliptin through systematic variations in the R1, R2, R3, R4, R5, and R6 substituents on the xanthine core. These structural parameter changes aim to optimize both the safety profile and bioavailability by altering molecular properties such as lipophilicity, molecular weight, and hydrogen bonding capacity, thereby improving absorption while maintaining low toxicity.
Solution Approach 2:
The patent applies local quality by introducing specific functional groups at particular positions on the xanthine molecule. Each substituent position (R1-R6) is independently optimized with specific groups (e.g., fluorine atoms, alkyl groups, alkoxy groups) to enhance local interactions with DPP-IV enzyme active site while improving overall drug metabolism and absorption characteristics.
2Reliability
If structural modification is made to linagliptin to improve bioavailability, then activity may increase, but complexity of structure increases
Solution Approach 1:
The patent applies segmentation by dividing the molecule modification into independent substituent positions (R1, R2, R3, R4, R5, R6) on the xanthine core. Each position can be independently optimized with specific functional groups, allowing systematic exploration of structure-activity relationships without creating overly complex molecular architectures. This modular approach enables precise control over activity enhancement while managing structural complexity.
Data Source
AI summary
The present invention relates to a Xanthine derivative as shown in formula (I),wherein,R is selected from:R1 is selected from cyano or methoxycarbonyl;R2 is selected from hydrogen and halogen atoms, a linear or branched C1-6 alkyl group which is substituted or unsubstituted by 1 to 5 halogen atoms, a linear or branched C1-6 alkoxy group which is substituted or unsubstituted by 1 to 5 halogen atoms;X and Y are each independently selected from C or N; andn is 0, 1, 2, 3 or 4.