Xanthine TRPC4/5 Modulators for Selective Ion Channel Regulation
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Solution Overview
Problem
Existing pharmaceuticals targeting TRPC4 and TRPC5 ion channels lack selectivity and efficacy in treating a range of diseases associated with abnormal function or expression, particularly in mental illnesses, neurological disorders, and other TRPC-related diseases.
Innovation Solution
Development of a class of xanthine compounds that act as regulators, specifically designed to inhibit or activate TRPC4 and TRPC5 channels, including inhibitors and agonists.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing pharmaceuticals targeting TRPC4 and TRPC5 ion channels are used, then some therapeutic effect is achieved, but selectivity and efficacy are insufficient
Solution Approach 1:
The patent modifies the chemical structure of xanthine compounds by changing parameters such as substituting hydrogen atoms at specific positions (e.g., 6-position with cycloalkyl groups, 7-position with heteroaryl groups) to achieve optimal balance between selectivity for TRPC4/5 channels and therapeutic efficacy across multiple disease indications
Solution Approach 2:
The invention creates composite molecular structures by combining xanthine core scaffold with various functional groups and substituents (cycloalkyl, heteroaryl, carbonyl groups) to produce compounds that simultaneously target TRPC4 and TRPC5 channels with high selectivity while addressing multiple pathologies
2Productivity
If TRPC4/5 inhibitors are developed to treat mental illnesses, then therapeutic efficacy is improved, but side effects and safety profile worsen
Solution Approach 1:
The patent introduces specific local structural features at particular positions of the xanthine molecule (e.g., cycloalkyl groups at 6-position, heteroaryl groups at 7-position) to create localized interactions that enhance selectivity for TRPC4/5 channels while minimizing off-target effects on other ion channels and receptors, thereby reducing side effects
Solution Approach 2:
The invention uses computational modeling and structure-activity relationship analysis to virtual screen and prioritize compounds with optimal binding characteristics to TRPC4/5 channels, selecting molecules that replicate successful lead compounds while improving safety profile through systematic molecular optimization
3Productivity
If TRPC5 inhibitors are used to treat kidney diseases, then proteinuria is reduced, but renal function and safety worsen
Solution Approach 1:
The patent optimizes pharmacokinetic parameters such as bioavailability, half-life, and dose-response characteristics of xanthine compounds to achieve sufficient TRPC5 channel inhibition for proteinuria reduction while maintaining safe renal function through controlled exposure and minimized off-target effects on other renal ion channels
4Reliability
If xanthine compounds are synthesized with complex structures, then selectivity and efficacy are improved, but manufacturing complexity and cost worsen
Solution Approach 1:
The patent divides the complex xanthine compound synthesis into modular steps, introducing functional groups and substituents in sequential stages (e.g., first establishing the xanthine core, then adding cycloalkyl groups at 6-position, followed by heteroaryl groups at 7-position), which simplifies the overall manufacturing process while maintaining high selectivity and efficacy
Data Source
Figure 1A~1B
Figure 2
Figure 3
AI summary
A xanthine compound and the use thereof. The structure of the compound is as shown in formula I-a, wherein the definition of each substituent is as described in the description and claims. The compound of formula I-a is an inhibitor or an agonist of TRPC4 and TRPC5 ion channels, and has a potential application value in preventing, delaying or treating diseases related to abnormal function or expression of TRPC4/5.