Substituted Condensed Azines Targeting Slo-1 Channels for Anthelmintic Control
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Solution Overview
Problem
The growing problem of anthelmintic resistance in veterinary medicine, particularly against nematodes, threatens effective worm control in animals and poses a risk to human helminth treatments due to the loss of efficacy of existing anthelmintic drugs, necessitating new molecular modes of action.
Innovation Solution
Development of novel compounds of general formula (I) that interact with Slo-1 channels of nematodes, causing paralysis and inhibition, offering a new mechanism for controlling gastro-intestinal and extra-intestinal helminth infections.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anthelmintic drugs are used extensively, then worm control is achieved, but resistance develops reducing efficacy
Solution Approach 1:
The patent applies parameter changes by developing compounds with novel molecular structures (general formula I) that differ from existing anthelmintic classes. This structural parameter change enables interaction with new targets (Slo-1 channels) and establishes a new mode of action, thereby overcoming resistance to conventional drugs while maintaining anthelmintic efficacy
Solution Approach 2:
The patent introduces an intermediary mechanism by targeting Slo-1 calcium channels as a mediator between the anthelmintic compound and the nematode. This intermediary target provides a new pathway for drug action that bypasses resistance mechanisms developed against direct targets of existing anthelmintics
2Reliability
If new anthelmintic compounds are developed, then resistance is overcome, but dosage requirements must be optimized
Solution Approach 1:
The patent optimizes dosage parameters by adjusting the molecular structure of compounds according to general formula I to achieve high potency. The structural parameters are modified to enhance binding affinity to Slo-1 channels, thereby reducing the quantity of substance required while maintaining effective anthelmintic activity
3Adaptability or versatility
If compounds are designed for broad spectrum activity, then coverage is improved, but selectivity and toxicity must be managed
Solution Approach 1:
The patent applies local quality by designing compounds that specifically target Slo-1 calcium channels present in nematodes. The molecular structure is optimized to interact with this specific target in helminths while minimizing interaction with mammalian physiological systems, thereby achieving broad spectrum anthelmintic activity with reduced toxicity to the treated organism
Data Source
AI summary
The present invention relates to novel anthelmintic compounds of general formula (I):T-L-A (I)wherein A is A1 or A2#2 indicates the binding position between the group L and A, T is a group T1-T6, L is a group L1-L10, and R1, R2, R3, R4, R5, R6 and Q 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 manufacturing pharmaceutical compositions 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.