CIC-1 Ion Channel Inhibitors for Neuromuscular Disorders

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Solution Overview

Problem

Current treatments for neuromuscular disorders, such as myasthenia gravis, are associated with deleterious long-term consequences and side effects, and there is a need for more effective drugs targeting the CIC-1 ion channel to restore neuromuscular transmission.

Innovation Solution

Development of novel compounds that inhibit the CIC-1 ion channel, specifically described by Formula (I), which are capable of restoring neuromuscular transmission and reversing muscle weakness caused by neuromuscular blockade or disorders like ALS and myasthenic conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for neuromuscular disorders are used, then neuromuscular function is improved, but deleterious long-term consequences and side effects occur

Engineering Contradiction:

Improveneuromuscular functionVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the therapeutic target parameter from acetylcholinesterase inhibition to CIC-1 chloride channel modulation. This fundamental parameter change in the treatment mechanism allows for improved neuromuscular function while avoiding the harmful side effects associated with conventional acetylcholinesterase inhibitors, particularly the long-term deleterious consequences mentioned in the background

Inventive Principle:

Principle #35Parameter changes

2Strength

If acetylcholinesterase inhibitors are administered to treat myasthenia gravis, then muscle strength is improved, but long-term deleterious consequences occur

Engineering Contradiction:

Improvemuscle strengthVSAvoidlong-term consequences

Core Design Contradiction:

StrengthVSDuration of action of stationary object

Solution Approach 1:

The patent extracts the therapeutic effect from the conventional acetylcholinesterase inhibition mechanism and isolates it into a distinct CIC-1 channel modulation approach. This extraction allows achieving muscle strength improvement through a different mechanism that does not produce the long-term deleterious consequences associated with acetylcholinesterase inhibitors

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces CIC-1 chloride channel modulation as an intermediary mechanism between the drug and the neuromuscular junction. This intermediary approach (modulating chloride conductance) provides a safer pathway to improve muscle strength without the harmful long-term effects of directly inhibiting acetylcholinesterase

Inventive Principle:

Principle #24Intermediary (Mediator)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

These compounds effectively improve or restore neuromuscular function, addressing muscle weakness and fatigue in neuromuscular junction disorders, with potential for reversing neuromuscular blockade and ameliorating conditions like myasthenia gravis and ALS.

Implementation Method 1

The compounds as defined herein preferably inhibit the CIC-1 ion channel

Methodology Applied

Scientific EffectIon channel inhibition:

Data Source

PatentUS12168643B2Compounds for the treatment of neuromuscular disorders

Publication Date: 2024.12.17 NMD PHARMA AS

AI summary

The present disclosure relates to compounds of Formula I:suitable for treating, ameliorating and/or preventing neuromuscular disorders, including the reversal of drug-induced neuromuscular blockade. The compounds as defined herein preferably inhibit the CIC-1 ion channel.