Pyrimidine Compounds as Selective Delta Opioid Receptor Modulators
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for new delta opioid receptor modulators as analgesics with reduced side effects, as well as delta and mu opioid receptor agonists and antagonists for treating various conditions including pain, immune function, esophageal reflux, cough, urological dysfunction, and respiratory diseases, with a requirement for compounds that can act as immunosuppressants, anti-inflammatory agents, and agents for neurological and psychiatric conditions.
Innovation Solution
Development of compounds of Formula (I) that include specific phenyl, pyrimidinyl, and pyridinyl substituents, which can act as delta and mu opioid receptor modulators, agonists, and antagonists, formulated into pharmaceutical compositions for use in treating a range of disorders with reduced side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If morphine and related opioids are used as analgesics, then pain relief is achieved, but side effects such as nausea, vomiting, drowsiness, and respiratory depression occur
Solution Approach 1:
The patent segments the opioid receptor system into distinct receptor types (delta, kappa, mu) and develops compounds that selectively target specific receptors. This segmentation allows for analgesic efficacy through delta receptor activation while avoiding side effects associated with mu receptor activation, such as respiratory depression and nausea
Solution Approach 2:
The patent applies local quality by designing compounds with specific molecular structures (Formula I with various substituent patterns) that confer selective affinity for delta opioid receptors. The local chemical structure determines the selective interaction with delta receptors, producing analgesia without the systemic side effects of non-selective opioids
2Object-generated harmful factors
If selective delta opioid receptor agonists are developed, then side effects are reduced, but new compounds with unexplored safety profiles are introduced
Solution Approach 1:
The patent develops a universal compound framework (Formula I) with multiple substituent variations that can produce different pharmacological effects. This multi-functionality allows the same core structure to serve as agonist, antagonist, or partial agonist depending on substituents, enabling comprehensive safety evaluation across multiple therapeutic scenarios
Data Source
AI summary
Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula I as follows: wherein R1, R2, R3, and L, A, and Ra are defined herein.