NLRP3 Inhibitor Compounds With Improved Potency and Specificity
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Solution Overview
Problem
Current treatments for NLRP3-related diseases, such as CAPS, type 2 diabetes, and atherosclerosis, lack compounds with improved pharmacological and physicochemical properties and offer limited potency and specificity in inhibiting the NLRP3 inflammasome.
Innovation Solution
Development of novel organic compounds, including those with specific structural features, that modulate NLRP3 inhibition, potentially offering enhanced therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for NLRP3-related diseases, then existing therapeutic options are available, but potency and specificity in inhibiting the NLRP3 inflammasome are limited
Solution Approach 1:
The patent applies parameter changes by systematically modifying the chemical structure of NLRP3 inhibitor compounds. The core pyridazin-3-amine scaffold is maintained while varying substituents at different positions (R1-R7 groups, heteroaryl rings, cycloalkyl groups) to optimize both potency/specificity for NLRP3 inhibition and pharmacological properties such as solubility, stability, and bioavailability. This structure-activity relationship optimization resolves the contradiction by achieving high NLRP3 specificity while maintaining versatile pharmacological characteristics.
2Reliability
If novel compounds with improved pharmacological properties are developed, then therapeutic efficacy is enhanced, but compound complexity increases
Solution Approach 1:
The patent employs segmentation by dividing the complex molecule into distinct functional modules: a core pyridazin-3-amine pharmacophore responsible for NLRP3 binding, various substituent groups (R1-R7) that modulate pharmacological properties, and optional heteroaryl or cycloalkyl components. This modular segmentation allows systematic optimization of therapeutic efficacy while managing structural complexity through combinatorial assembly of predefined building blocks.
Solution Approach 2:
The patent achieves universality through the versatile pyridazin-3-amine core structure that can accommodate multiple different substituent patterns while maintaining NLRP3 inhibition activity. This universal scaffold allows a single molecular framework to serve multiple therapeutic purposes by simply changing the substituent groups, thereby enhancing therapeutic efficacy without proportionally increasing fundamental structural complexity.
Data Source
AI summary
The invention relates to novel compounds having the general formula (Ib) or (Ib′), (Ib) or (Ib′) wherein R1, R2, R6, A3, A4, A5, X, Y and W are as described herein, composition including the compounds and methods of using the compounds.