Carboxylic Diarythiazepineamines Dual MOR-DOR Agonism

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current mu opioid receptor (MOR) agonists used for pain treatment suffer from tolerance development, high addiction liability, and side effects such as respiratory depression, nausea, and constipation, while also having limited efficacy for depression and borderline personality disorder.

Innovation Solution

A compound with a specific structure that can activate both mu-opioid and delta-opioid receptors, offering improved therapeutic profiles for pain management, depression, and borderline personality disorder, potentially reducing addiction risk and side effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If morphine-derived MOR agonists are used for pain treatment, then analgesic effects are achieved, but tolerance development, addiction liability, and side effects (respiratory depression, nausea, constipation) occur

Engineering Contradiction:

Improveanalgesic efficacyVSAvoidaddiction liability and side effects

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent combines activation of two opioid receptor types (MOR and DOR) into a single compound. The diarythiazepineamine structure simultaneously engages both MOR and DOR, merging the therapeutic effects of MOR agonism (analgesia) with the favorable profile of DOR agonism (lower addiction potential, fewer side effects), thereby resolving the contradiction between efficacy and harmful effects

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The compound serves multiple functions by acting as a dual agonist at both MOR and DOR. This multi-functionality allows the single agent to provide analgesic effects through MOR while simultaneously leveraging DOR activation to reduce tolerance and addiction liability, addressing multiple therapeutic needs with one compound

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If MOR agonists are used for depression treatment, then antidepressant effects may be achieved, but the same side effects and tolerance issues occur

Engineering Contradiction:

Improveantidepressant efficacyVSAvoidaddiction liability and side effects

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The compound merges MOR and DOR activation to treat depression. While MOR activation can produce antidepressant effects, combining it with DOR activation provides a more favorable side effect profile and reduced addiction potential, as DOR agonists have been shown to have lower abuse liability

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The diarythiazepineamine compound represents a composite molecular structure that integrates pharmacophores capable of interacting with both MOR and DOR. This composite structure enables simultaneous engagement of both receptor systems to achieve antidepressant effects with improved safety and tolerability

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS11787772B2Carboxylic diarythiazepineamines as mixed mu- and delta-opioid receptor agonists

Publication Date: 2023.10.17 THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK

AI summary

The present invention provides a compound having the structure:or a pharmaceutically acceptable salt or ester thereof, and a method of treating a subject afflicted with a pain, a depressive disorder, a mood disorder, an anxiety disorder, borderline personality disorder, opioid addiction, or opioid withdrawal symptoms by administering the compound to the subject.