Morphinan Derivative Selective δ Receptor Agonist
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Solution Overview
Problem
Current antidepressants and anxiolytic drugs have limitations such as high adverse effects, dependence, and limited efficacy, and existing analgesics often cause respiratory depression and other side effects, necessitating the development of a medication that can effectively treat depression, anxiety, and pain with reduced adverse effects.
Innovation Solution
A compound represented by the general formula (I) with specific structural features that selectively activates the opioid δ receptor, minimizing activation of μ and κ receptors, thereby reducing adverse effects and providing potent antidepressive, anxiolytic, and analgesic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If morphine is used to activate opioid μ receptor for analgesic effect, then analgesic potency is improved, but adverse effects such as dependence, respiratory depression, and gastrointestinal suppression worsen
Solution Approach 1:
The invention segments the opioid receptor system into distinct subtypes (μ, δ, κ) and develops compounds that selectively target only the δ receptor. This segmentation allows achieving analgesic effects through δ receptor activation while avoiding the adverse effects associated with μ and κ receptor activation, thus resolving the contradiction between efficacy and safety
Solution Approach 2:
The patent applies local quality by designing compounds with specific molecular structures (general formula I) that exhibit high selectivity for the δ receptor subtype. The local structural features of the compound enable preferential binding to δ receptors in pain pathways while minimizing interaction with μ and κ receptors, thereby achieving targeted analgesia with reduced side effects
2Reliability
If eptazocine is used to activate opioid κ receptor for analgesic effect, then analgesic potency is improved, but adverse effects such as sweating, nausea, vomiting, and thirst worsen
Solution Approach 1:
The invention segments the opioid receptor system into distinct subtypes (μ, δ, κ) and develops compounds that selectively target only the δ receptor. This segmentation allows achieving analgesic effects through δ receptor activation while avoiding the adverse effects associated with μ and κ receptor activation, thus resolving the contradiction between efficacy and safety
3Reliability
If existing antidepressants are used to treat depression and anxiety, then some therapeutic effect is achieved, but adverse effects, dependence, and limited efficacy worsen
Solution Approach 1:
The invention applies universality by developing a δ receptor agonist that simultaneously provides multiple therapeutic benefits including antidepressive, anxiolytic, and analgesic effects. This multi-functional compound addresses several psychiatric and pain conditions with a single mechanism of action, improving therapeutic versatility while maintaining a favorable safety profile
4Reliability
If conventional analgesics are used to treat pain, then analgesic effect is achieved, but respiratory depression and other side effects worsen
Solution Approach 1:
The invention segments the opioid receptor system into distinct subtypes (μ, δ, κ) and develops compounds that selectively target only the δ receptor. This segmentation allows achieving analgesic effects through δ receptor activation while avoiding the adverse effects associated with μ and κ receptor activation, thus resolving the contradiction between efficacy and safety
Data Source
AI summary
A morphinan derivative represented by the following general formula (I):wherein R1 represents hydrogen, C1-10 alkyl, cycloalkylalkyl where the cycloalkyl moiety has 3 to 6 carbon atoms, and the alkylene moiety has 1 to 5 carbon atoms, etc.; R2 represents heterocyclic ring containing 1 to 4 heteroatoms selected from N, O and S and at least one carbon atom as ring-constituting atoms, containing at least one set of adjacent ring-constituting atoms bound by a double bond, and further substituted with at least one oxo group; Y binds to a carbon atom as a ring-constituting atom of R2; R3, R4, and R5 represent hydrogen, hydroxy, etc.; R6a and R6b represent hydrogen, etc.; R7 and R8 represent hydrogen, etc.; R9 and R10, which are the same or different, represent hydrogen, etc.; X represents O or CH2; and Y represents C(═O)); a tautomer or stereoisomer of the compound, or a pharmaceutically acceptable salt thereof, or a solvate thereof is used as an anxiolytic drug, antidepressant, etc.