6,7-Cyclicmorphinan Derivatives for Opioid Receptor Modulation
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Solution Overview
Problem
Current pain management options, particularly for chronic pain, often rely on opioid analgesics that can cause central side effects and have limitations in targeting specific opioid receptors, such as κ-opioid receptors, leading to a need for more effective analgesics that act on both central and peripheral opioid receptors with reduced side effects.
Innovation Solution
Development of compounds represented by Formulae I to XIV, which act as modulators of μ, δ, κ, and ORL-1 opioid receptors, allowing for the treatment of pain and other conditions by administering these compounds to modulate opioid receptors centrally or peripherally, thereby providing analgesia with reduced central side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If centrally penetrating κ agonists are used to treat pain, then analgesic effects are improved, but sedative and psychotomimetic side effects increase
Solution Approach 1:
The patent applies segmentation by developing compounds with selective affinity for specific opioid receptor subtypes (μ, δ, κ, ORL-1) rather than non-selective agonists. This allows targeted modulation of pain pathways while minimizing activation of receptors responsible for side effects, thus segmenting the therapeutic effect from adverse effects.
Solution Approach 2:
The patent employs local quality by designing compounds with specific molecular structures (Formulae I-XIV) that exhibit preferential binding to particular opioid receptor subtypes. This localized receptor selectivity enables the compound to produce analgesia through specific receptor interactions while avoiding broader CNS effects that cause sedation and psychotomimetic symptoms.
2Reliability
If opioid analgesics are administered to manage chronic pain, then pain relief is improved, but central side effects increase
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure and pharmacological properties of opioid compounds to achieve selective receptor binding profiles. The compounds in Formulae I-XIV are designed with specific molecular parameters that confer selectivity for pain-related opioid receptors while reducing affinity for receptors mediating central side effects, thus changing the therapeutic parameter profile.
3Adaptability or versatility
If non-selective opioid receptor agonists are used, then broad analgesic coverage is improved, but specificity for target receptor types decreases
Solution Approach 1:
The patent employs local quality by designing compounds with specific molecular structures (Formulae I-XIV) that exhibit preferential binding to particular opioid receptor subtypes. This localized receptor selectivity enables the compound to produce analgesia through specific receptor interactions while avoiding broader CNS effects that cause sedation and psychotomimetic symptoms.
Solution Approach 2:
The patent applies parameter changes by modifying the chemical structure and pharmacological properties of opioid compounds to achieve selective receptor binding profiles. The compounds in Formulae I-XIV are designed with specific molecular parameters that confer selectivity for pain-related opioid receptors while reducing affinity for receptors mediating central side effects, thus changing the therapeutic parameter profile.
Data Source
AI summary
The application provides compounds of Formula I and pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, R3, R4, R5, dash line a, dash line b, W, Z, X, and m are defined as set forth in the specification. The invention is also directed to use of the compounds of Formula I and the pharmaceutically acceptable salts and solvates thereof to treat disorders responsive to the modulation of one or more opioid receptors, or as synthetic intermediates. In certain embodiments, the Compounds of the Invention are useful for treating pain.