Slo-1-Targeting Anthelmintic Compounds for Resistant Nematodes

Solution Overview

Problem

The growing resistance of helminths to existing anthelmintics in veterinary and human medicine necessitates the development of new compounds with improved anthelmintic activity against a broad spectrum of helminths, particularly at low dosages, without adverse toxic effects.

Innovation Solution

Compounds of general formula (I) that interact with Slo-1 of nematodes, leading to paralysis or inhibition of gastro-intestinal nematodes and filariae, offering effective control, treatment, and prevention of helminth infections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing anthelmintics are used to control helminth infections, then anthelmintic activity is achieved, but resistance develops in helminth populations

Engineering Contradiction:

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by developing compounds with novel chemical structures (general formula I) that differ from existing anthelmintic classes. These compounds interact with Slo-1 calcium channels, representing a change in the molecular target parameter, thereby achieving anthelmintic activity against resistant helminth populations while maintaining reliability of treatment

Inventive Principle:

Principle #35Parameter changes

2Reliability

If anthelmintic dosages are increased to overcome resistance, then anthelmintic activity improves, but toxic effects increase

Engineering Contradiction:

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent achieves selective toxicity by designing compounds that specifically target Slo-1 calcium channels in helminths. This parameter change in target specificity allows effective anthelmintic activity at low dosages without proportionally increasing toxic effects on the host, as the novel chemical structures and mechanism of action provide selective advantage

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces an intermediary mechanism by targeting Slo-1 calcium channels, which are specific to helminth physiology. This intermediary target allows the compound to mediate its anthelmintic effect selectively on helminths while sparing the host, thereby maintaining high reliability of activity without proportional increase in toxic effects

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

The compounds effectively inhibit gastro-intestinal and extra-intestinal nematodes, including filariae, providing a solution to anthelmintic resistance issues with minimal toxicity.

Implementation Method 1

Compounds of general formula (I) that interact with Slo-1 of nematodes, leading to paralysis or inhibition of gastro-intestinal nematodes and filariae

Methodology Applied

Scientific EffectIon channel interaction:

Data Source

PatentUS12435068B2Anthelmintic compounds

Publication Date: 2025.10.07

AI summary

The present invention relates to novel compounds of general formula (I):withA being A1 or A2:andin which T, X, Y, Ro, R1, R10 and R11 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for the treatment, control and/or prevention of diseases, in particular of helminth infections, as a sole agent or in combination with other active ingredients.