TRPV1 Antagonists with Dihydroxy Substituent for Pain and Inflammation
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Solution Overview
Problem
Current treatments for pain, urinary incontinence (UI), ulcers, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS) often have incomplete success and are associated with significant side effects.
Innovation Solution
Development of new compounds that exhibit affinity for the TRPV1 receptor, specifically acting as antagonists to treat chronic or acute pain, UI, ulcers, IBD, and IBS, with reduced side effects compared to existing treatments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional pain treatments (non-opioid or opioid analgesics) are administered, then pain relief is achieved, but significant side effects occur
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of TRPV1 antagonist compounds, specifically incorporating a 3,4-dihydroxy substituent pattern that optimizes binding affinity and selectivity for the TRPV1 receptor. This structural parameter optimization enables effective pain relief while reducing off-target effects and side effects compared to traditional analgesics
Solution Approach 2:
The patent uses TRPV1 receptor antagonists as intermediary compounds that selectively block the TRPV1 channel without activating it. These compounds act as mediators between the pain signal and the nervous system, providing analgesia through a different mechanism than traditional opioids or NSAIDs, thereby avoiding their associated side effects
2Reliability
If H2 antagonists are used to treat ulcers, then gastric acid secretion is reduced, but multiple adverse side effects occur
Solution Approach 1:
The patent extracts the beneficial ulcer-healing effect (reduced gastric acid secretion) while eliminating the harmful side effects by using TRPV1 antagonists with a specific 3,4-dihydroxy substituent structure. This selective compound targets the TRPV1 receptor involved in pain and inflammation pathways without affecting H2 receptors, thereby achieving ulcer treatment without the side effects of H2 antagonists
3Reliability
If existing UI treatments are administered, then bladder-detrusor-muscle overactivity is controlled, but complete success is not achieved and significant adverse side effects occur
Solution Approach 1:
The patent optimizes the chemical parameters of TRPV1 antagonist compounds by incorporating a 3,4-dihydroxy substituent, which enhances receptor binding affinity and selectivity. This parameter optimization enables more effective control of bladder-detrusor-muscle overactivity while minimizing adverse side effects compared to existing UI treatments
Data Source
AI summary
The disclosure relates to Compounds of Formula (I):and pharmaceutically acceptable derivatives thereof wherein Ar1, Ar2, L1, L2, X, R3, R22, and m are as defined herein, compositions comprising an effective amount of a Compound of Formula (I), and methods for treating or preventing a condition such as pain, UI, an ulcer, IBD and IBS, comprising administering to an animal in need thereof an effective amount of a Compound of Formula (I).