Selective Tetrapeptide Kappa Agonists With Reduced Opioid Side Effects
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Solution Overview
Problem
Existing kappa-opioid receptor agonists suffer from side effects such as respiratory depression, dependence, addiction, constipation, diuresis, sedation, and dysphoria, limiting their efficacy in treating medical disorders like pain, depression, autoimmune disorders, and neurological diseases.
Innovation Solution
Development of novel tetrapeptide compounds with specific structural modifications, including acyl coupling and deprotection reactions, to create selective kappa-opioid receptor agonists that minimize these side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional opioid analgesics are used, then analgesic effect is achieved, but side effects such as respiratory depression, dependence, and addiction occur
Solution Approach 1:
The patent modifies the molecular structure of traditional opioid analgesics by changing chemical parameters (adding specific substituents at defined positions) to create compounds that selectively activate kappa-opioid receptors while reducing activation of mu-opioid receptors, thereby maintaining analgesic effects while minimizing side effects like respiratory depression and addiction
Solution Approach 2:
The invention segments the opioid receptor binding interaction by designing compounds with specific structural features that target kappa-receptors separately from mu-receptors, allowing selective activation of the desired receptor subtype while avoiding activation of receptors responsible for harmful side effects
2Object-generated harmful factors
If kappa-opioid receptor agonists are developed to avoid traditional opioid side effects, then side effect profile is improved, but efficacy is reduced leading to clinical trial failures
Solution Approach 1:
The patent applies local quality by introducing specific substituents at particular positions (e.g., position 1 with cyano group, position 2 with fluorine) on the molecular structure to optimize the balance between kappa-receptor selectivity and analgesic efficacy, ensuring the compound maintains therapeutic effectiveness while avoiding harmful side effects
3Reliability
If selective kappa-opioid receptor agonists are synthesized with modified molecular structures, then selectivity is improved, but manufacturing complexity increases
Solution Approach 1:
The patent employs preliminary action by pre-installing protecting groups (such as BOC and FMOC) on amino acid residues before peptide coupling reactions, and using pre-synthesized building blocks with defined stereochemistry, which simplifies the overall synthesis process while maintaining high selectivity and purity of the final kappa-opioid receptor agonist
Data Source
AI summary
The present invention provides compounds which are selective kappa-opioid receptor agonist, method of preparation of these compounds, compositions that comprise these compounds, and methods for treating kappa-opiod receptor agonist related medical disorders.