Purine Dione Wnt Modulators for Selective Pathway Inhibition
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Solution Overview
Problem
There is a need for compounds that modulate or inhibit Wnt activity to treat diseases associated with Wnt pathway dysregulation, including various cancers and fibrotic diseases.
Innovation Solution
Development of purine dione compounds with specific structural features that can modulate Wnt activity by targeting the Wnt pathway, including various aryl and heteroaryl groups, to regulate cellular functions and treat associated diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Wnt signalling is inhibited to treat diseases, then therapeutic benefit is achieved, but stem cell proliferation and maintenance are blocked
Solution Approach 1:
The patent applies local quality by developing compounds with specific structural modifications at different positions of the purine dione core structure. Different substituents (R1-R6 groups) are introduced to create compounds with differentiated properties that can selectively modulate Wnt pathway activity in specific tissue contexts, potentially achieving therapeutic effects while preserving stem cell function in critical tissues.
Solution Approach 2:
The patent employs parameter changes by systematically varying chemical parameters of the purine dione compounds, including substituent types, positions, and configurations. This allows optimization of compound properties to achieve selective Wnt pathway modulation - potentially differentiating between pathological Wnt activation in diseases versus physiological Wnt signalling in stem cell maintenance.
2Reliability
If purine dione compounds are developed with specific structural features, then Wnt activity modulation is achieved, but compound complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the purine dione compound into distinct functional modules with specific substituent groups (R1-R6). Each substituent can be independently optimized for specific properties such as binding affinity, selectivity, and pharmacokinetic characteristics, allowing systematic development of compounds with tailored Wnt modulation activities.
Solution Approach 2:
The patent employs universality by designing a core purine dione structure that can accommodate multiple different substituent patterns, creating a versatile scaffold capable of modulating Wnt pathway activity through various mechanisms. This multi-functional approach allows a single compound series to address multiple aspects of Wnt pathway dysregulation in different diseases.
Data Source
AI summary
The invention relates to the use of compounds of general structure (I) in modulation of the Wnt pathwaywherein R1, R2, R3, R4 and R5 are each, independently, H or an alkyl group; D is selected from the group consisting of H, halogen, alkyl, cycloalkyl, aryl, and dialkylamino, each (other than H and halogen) being optionally substituted; Ar is an aryl or heteroaryl group, optionally substituted; Cy is an aryl, heteroaryl or a saturated ring containing at least one heteroatom, each being optionally substituted; and n is an integer from 1 to 3.