Aryl Pyridine Nav1.7/Nav1.8 Blockers for Neuropathic Pain Relief
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Solution Overview
Problem
Current treatments for neuropathic pain are limited by adverse effects and low efficacy, and there is a need for new compounds that can effectively block Nav 1.7 and/or Nav 1.8 sodium channels to manage pain-related pathologies with reduced side effects.
Innovation Solution
Development of aryl pyridine compounds with blocking activity against Nav 1.7 and/or Nav 1.8 channels, which are used in compositions and kits for treating neuropathic pain, with potential processes for their preparation and administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If opioid analgesics and adjuvant medications are used to treat neuropathic pain, then pain relief is achieved, but adverse effects increase and efficacy is limited
Solution Approach 1:
The patent extracts and targets specific sodium channel subtypes (Nav 1.7 and Nav 1.8) that are predominantly expressed in nociceptive neurons, rather than using non-selective opioid analgesics. This selective blocking approach isolates the therapeutic action to pain pathways while sparing other physiological functions, thereby improving efficacy and reducing adverse effects associated with broad-spectrum opioid activity
Solution Approach 2:
The invention applies local quality by designing compounds with selective affinity for specific sodium channel isoforms (Nav 1.7 and/or Nav 1.8) in nociceptive neurons. This selective blocking provides localized therapeutic action on pain transmission pathways while maintaining normal function in other neuronal populations, thus achieving reliable pain relief with minimized systemic adverse effects
2Reliability
If non-selective sodium channel blockers are used, then pain relief is achieved, but adverse effects such as migraine, epilepsy, paralysis, and cardiac syndromes occur
Solution Approach 1:
The patent implements local quality by developing compounds that selectively block Nav 1.7 and/or Nav 1.8 sodium channel subtypes which are specifically expressed in nociceptive neurons. This selective action confines the therapeutic effect to pain pathways while avoiding blockade of other sodium channels in the brain, heart, and muscles, thereby achieving effective pain relief without the systemic adverse effects of non-selective blockers
Solution Approach 2:
The invention applies segmentation by targeting specific subsets of sodium channels (Nav 1.7 and Nav 1.8 isoforms) rather than all voltage-gated sodium channels. This segmented approach divides the broad class of sodium channels into therapeutic targets (pain-related subtypes) and non-targets (critical functions in heart, brain, muscles), enabling selective pain relief with reduced risk of adverse effects
Data Source
AI summary
The present invention relates to aryl pyridine blocking compounds of Nav 1.7 and/or Nav 1.8. More specifically, the present invention is related to aryl pyridines comprising Formula (I), in which the substituents R1 to R10 are selected independently of the groups defined in the specification, as well as their preparation processes, compositions comprising at least one of these compounds, uses, treatment methods to treat or prevent pain-related pathologies and kits. The present invention belongs to the fields of medicinal chemistry, organic synthesis, as well as to the treatment of pain-related diseases.