Morphinan Compounds Targeting Opioid Receptors for Pruritus Relief
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Solution Overview
Problem
Current treatments for pruritus, or itch, are inadequate as the underlying causes are not fully understood, and existing solutions do not effectively address the condition's complexity, particularly in cases involving anemia, erythropoietin deficiency, histamine release, skin dryness, secondary hyperparathyroidism, and opioid receptor alterations.
Innovation Solution
Development of compounds with specific structural formulas, such as those represented by (I) and (II), which are used in pharmaceutical compositions and dosage forms, including topical and extended-release formulations, to treat pruritus and gastrointestinal conditions by targeting opioid receptors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for pruritus are used, then general symptom relief may be achieved, but the underlying complexity of the condition involving multiple pathogenic factors is not effectively addressed
Solution Approach 1:
The patent applies universality by developing a single compound (Formula I) that can address multiple pathogenic factors associated with pruritus. The compound is designed to interact with various receptors including opioid receptors, histamine receptors, and other targets involved in itch pathways, allowing one treatment to potentially address anemia-related pruritus, histamine release, skin dryness, and opioid receptor alterations simultaneously
2Reliability
If μ-opioid receptor antagonists are used for treating pruritus, then relief from itch sensation may be achieved, but potential side effects and lack of selectivity remain concerns
Solution Approach 1:
The patent applies local quality by designing a compound with specific structural features (Formula I) that enable selective interaction with particular receptor subtypes. The molecular structure includes specific functional groups and spatial arrangement that confer preferential binding to certain opioid receptors while minimizing interaction with others, thereby achieving localized therapeutic effect at the receptor level while reducing systemic side effects
Solution Approach 2:
The patent applies parameter changes by modifying key molecular parameters of the compound including the substituent R1 at position 1 of the morphinan core structure. By varying this parameter and other structural features, the compound's affinity and selectivity for different opioid receptors can be tuned, optimizing the balance between pruritus relief and side effect profile
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compounds provide effective relief from pruritus and gastrointestinal conditions by selectively binding to opioid receptors, offering a targeted approach to managing itch and reducing symptoms with minimal systemic activity.
Implementation Method 1
The compounds provide effective relief from pruritus and gastrointestinal conditions by selectively binding to opioid receptors
Data Source
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AI summary
The present invention includes compounds having structural formula (I), or pharmaceutically acceptable salts, solvates, and/or esters thereof. These compounds are useful for treating itch or a pruritic condition. The present invention also includes compositions comprising the present compounds and methods of treating a pruritic condition. Furthermore, the present invention provides methods for preparing the compounds.