Quinoline Ion Channel Modulators for Pain Relief

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Solution Overview

Problem

Current sodium channel and calcium channel blockers for pain management have limited efficacy due to side effects such as CNS disturbances, cardiac arrhythmias, and cardiac failure, and there is a need for more potent compounds with fewer side effects.

Innovation Solution

Development of compounds that inhibit voltage-gated sodium channels and calcium channels, specifically represented by formulas IA, IB, IC, and ID, which are designed to treat various pain conditions and disorders with improved potency and reduced side effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current sodium channel and calcium channel blockers are used for pain management, then pain relief is achieved, but side effects such as CNS disturbances, cardiac arrhythmias, and cardiac failure occur

Engineering Contradiction:

Improvepain relief efficacyVSAvoidside effects (CNS disturbances, cardiac arrhythmias, cardiac failure)

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by developing novel chemical compounds with modified molecular structures (formulas IA, IB, IC, ID) that alter the pharmacological parameters of channel blocking. These structural modifications enable the compounds to achieve effective pain relief while reducing affinity for off-target receptors, thereby minimizing CNS disturbances and cardiac side effects compared to conventional blockers

Inventive Principle:

Principle #35Parameter changes

2Reliability

If more potent channel blockers are developed to improve pain management, then efficacy is enhanced, but risk of harmful side effects increases

Engineering Contradiction:

Improvepain management efficacyVSAvoidcardiac arrhythmias and cardiac failure

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by designing compounds with specific functional groups and molecular features that confer selective affinity for sodium and calcium channels in pain pathways while reducing interaction with cardiac channels. The structural parameters (substituents R1-R6, ring systems) are optimized to create localized chemical properties that enhance pain relief potency while sparing cardiac tissue from harmful effects

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS8372843B2Quinolines useful as modulators of ION channels

Publication Date: 2013.02.12 VERTEX PHARMACEUTICALS INC

AI summary

The present invention relates to compounds useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.