1,2-Bis-Sulfonamide Derivatives for Ocular Inflammation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current broad spectrum chemokine inhibitors, primarily peptides, have limitations such as low potency, poor pharmacokinetics, and instability in vivo, making them unsuitable for long-term therapeutic use, especially when systemic administration can lead to deleterious side effects, and there is a need for a more effective and targeted approach to treat ocular inflammatory diseases like uveitis, diabetic retinopathy, and dry eye.
Innovation Solution
Development of novel 1,2-bis-sulfonamide derivatives that act as potent and selective chemokine receptor modulators, capable of modulating chemokine receptor activity, which can be used to treat a variety of disorders associated with chemokine receptor modulation, including ocular inflammatory diseases, with improved stability and reduced systemic side effects through local or topical application.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If peptide-based chemokine inhibitors are used, then broad spectrum chemokine inhibition is achieved, but potency is low and pharmacokinetics are poor
Solution Approach 1:
The patent transforms peptide-based chemokine inhibitors into small molecule 1,2-bis-sulfonamide derivatives, fundamentally changing the chemical parameters (molecular size, structure, properties) to achieve improved potency and pharmacokinetics while maintaining chemokine receptor modulation activity
Solution Approach 2:
The patent creates small molecule compounds that copy the functional effect of peptide-based chemokine inhibitors (chemokine receptor modulation) but with superior pharmacological properties including higher potency, better stability, and improved pharmacokinetic profile
2Reliability
If systemic administration of chemokine inhibitors is used, then therapeutic effect is achieved, but deleterious side effects occur
Solution Approach 1:
The patent enables local or topical administration of the small molecule chemokine inhibitors to the eye, creating a localized therapeutic effect that treats ocular inflammatory diseases while minimizing systemic exposure and associated side effects
3Reliability
If peptide-based chemokine inhibitors are used, then chemokine receptor modulation is achieved, but stability in vivo is poor
Solution Approach 1:
The patent changes the chemical composition from peptides to small molecule 1,2-bis-sulfonamide derivatives, which possess superior metabolic stability, chemical stability, and pharmacokinetic properties while maintaining the ability to modulate chemokine receptors
Data Source
AI summary
The present invention relates to novel bis-sulfonamide derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of chemokine receptors.