Pyrazole CFTR Modulators for Mutation-Specific Cystic Fibrosis
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Solution Overview
Problem
Current treatments for cystic fibrosis, particularly those targeting the F508del-CFTR mutation, have limited therapeutic efficacy, necessitating the development of customized CFTR modulators for specific genetic sub-groups of patients.
Innovation Solution
Development of novel pyrazole derivatives that act as CFTR modulators, including correctors and potentiators, to address the trafficking and gating defects caused by CFTR mutations, such as F508del.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current CFTR modulators are used to treat F508del-CFTR mutation, then some therapeutic effect is achieved, but the therapeutic efficacy is limited
Solution Approach 1:
The patent segments the CFTR modulator market into different classes (correctors and potentiators) targeting specific mutation types. The compounds are designed to address particular trafficking and gating defects associated with specific CFTR mutations, enabling customized treatment approaches for different genetic sub-groups of cystic fibrosis patients.
Solution Approach 2:
The patent applies local quality by designing compounds with specific molecular structures (pyrazole derivatives with particular substituent patterns) that target specific defects in CFTR protein function. Different compounds within the series are optimized for different mutation types, providing localized therapeutic solutions for specific genetic variants rather than a universal approach.
2Adaptability or versatility
If novel pyrazole derivatives are developed as CFTR modulators, then targeted therapeutic approach is achieved, but development complexity increases
Solution Approach 1:
The patent employs a universal scaffold (pyrazole ring structure) that can serve multiple functions by incorporating different substituents. The core pyrazole structure provides the basis for both corrector and potentiator activities, allowing a single molecular framework to address multiple aspects of CFTR dysfunction across different mutation types through systematic substitution patterns.
Data Source
AI summary
The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof:It further discloses a pharmaceutical composition comprising the compounds of Formula (I) and their uses, in particular to modulate CFTR protein or ABC protein activities.