Orvinol Derivatives Modulating Opioid Receptors
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Solution Overview
Problem
Current treatments for drug and alcohol abuse, particularly opioid abuse, lack effective compounds that are potent mu opioid receptor antagonists without significant agonist activity, and have limited options for preventing relapse in recovering addicts.
Innovation Solution
Development of novel orvinol and thevinol compounds with specific structural modifications, including aryl substituents at R2 and R3, which are mu opioid receptor antagonists and kappa opioid receptor antagonists, and have activity at the NOP/ORL-1 receptor, designed to address the limitations of existing treatments by providing a unique pharmacological profile.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If buprenorphine is used for treatment, then mu opioid receptor agonist activity is provided, but significant agonist activity cannot be reduced without losing therapeutic effectiveness
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of orvinol compounds, specifically varying substituents at positions R1-R6 to tune the balance between agonist and antagonist activity. This allows optimization of therapeutic effectiveness while controlling harmful agonist activity through systematic structural modification.
Solution Approach 2:
The patent applies local quality by introducing specific substituents at particular positions on the morphinan core structure. Different substituents at R1-R6 positions create localized changes in receptor interaction, enabling selective modulation of agonist versus antagonist properties at different sites of the molecule.
2Adaptability or versatility
If existing treatment compounds are used, then treatment for opioid abuse is provided, but options for preventing relapse in recovering addicts are limited
Solution Approach 1:
The patent applies universality by designing orvinol derivatives that can serve multiple therapeutic functions: treating active opioid abuse, preventing relapse in recovering addicts, and potentially addressing other substance use disorders. The compounds exhibit broad applicability across different treatment scenarios.
Solution Approach 2:
The patent applies dynamics by creating a series of compounds with varying degrees of agonist and antagonist activity. This dynamic range allows clinicians to select appropriate compounds based on the specific treatment phase and patient needs, whether acute detoxification or long-term relapse prevention.
3Ease of manufacture
If compounds with limited structural variations are used, then synthesis is simplified, but the range of pharmacological profiles is restricted
Solution Approach 1:
The patent applies segmentation by dividing the molecule into a core morphinan structure and variable substituent groups at positions R1-R6. This modular approach allows independent optimization of each segment, simplifying synthesis of the core while enabling diverse pharmacological profiles through combinatorial substitution patterns.
Data Source
AI summary
The invention provides a method of treating drug and alcohol abuse, depression, anxiety, or a compulsive disorder in a subject comprising administering to the subject a compound having the formula:or a pharmaceutically acceptable salt or solvate thereof, wherein R, R1, R2, R3, R4, R5, and X are as defined in the specification.