Peptidomimetics for Opioid Receptor Modulation

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Solution Overview

Problem

Current opioid-based pain treatments are limited by severe side effects such as dependence, tolerance, and adverse reactions, necessitating the development of analgesics with reduced or no side effects.

Innovation Solution

Development of peptidomimetic compounds that act as mu-opioid receptor agonists, delta-opioid receptor antagonists, or dual mu-opioid receptor agonist/delta-opioid receptor antagonist agents, which modulate opioid receptors to provide pain relief without the side effects associated with traditional opioids.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional opioid drugs (e.g., morphine) are used for pain treatment, then effective pain relief is achieved, but severe side effects occur including dependence, tolerance, and adverse reactions

Engineering Contradiction:

Improvepain relief effectivenessVSAvoidside effects including dependence and tolerance

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention segments the opioid receptor system into multiple subtypes (MOR, DOR, KOR) and develops compounds that can selectively target specific combinations of these receptors. By dividing the single-receptor-targeting approach into multi-receptor-selective approaches, the patent achieves pain relief through MOR activation while avoiding dependence and tolerance through DOR antagonism, thus resolving the contradiction between effectiveness and harmful side effects

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent changes the pharmacological parameters of opioid receptor modulation by developing compounds with dual or triple activity profiles (e.g., MOR agonist/DOR antagonist, MOR agonist/KOR antagonist). This parameter change from single-receptor agonism to multi-receptor selective modulation allows maintaining analgesic effectiveness while eliminating the development of dependence and tolerance associated with traditional opioids

Inventive Principle:

Principle #35Parameter changes

2Reliability

If opioid drugs are used to treat pain, then analgesic effect is achieved, but the development of dependence and tolerance occurs

Engineering Contradiction:

Improveanalgesic effectVSAvoidduration of dependence and tolerance development

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The invention applies preliminary anti-action by incorporating DOR antagonist or KOR antagonist activity into compounds that also possess MOR agonist activity. This preemptive blocking of DOR/KOR prevents the neuroadaptive changes that lead to dependence and tolerance before they can develop, while still providing effective analgesia through MOR activation

Inventive Principle:

Principle #9Preliminary anti-action

Solution Approach 2:

The patent creates multi-functional compounds that simultaneously act as MOR agonists (providing analgesia) and DOR/KOR antagonists (preventing dependence and tolerance). This universality allows a single compound to address multiple aspects of opioid therapy - both therapeutic benefit and harm prevention - resolving the contradiction between sustained analgesic effect and prevention of long-term adverse outcomes

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS10519114B2Peptidomimetics and methods of using the same

Publication Date: 2019.12.31 THE RGT UNIV OF MICHIGAN

AI summary

Disclosed herein are compounds useful for modulating the mu-opioid receptor (“MOR”) and/or delta-opioid receptor (“DOR”), and methods of using these compounds to treat diseases and conditions, such as pain. In particular, disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salt thereof:wherein the substituents are as described.