4-Hydroxybenzomorphans with Carboxamide Groups for Opioid Receptor Affinity

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

The removal or replacement of the phenolic 3-hydroxyl group in opioid receptor-interactive compounds typically results in pharmacologically inactive compounds, limiting the development of effective analgesics and addiction treatments.

Innovation Solution

Substituting the 3-position with small, polar, neutral residues such as carboxamide or thiocarboxamide groups, allowing for the introduction of a hydroxyl at the 4-position, which enhances opioid receptor affinity and activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If the phenolic 3-hydroxyl group is removed or replaced in opioid receptor-interactive compounds, then the compounds become pharmacologically inactive, but this structural modification was attempted to develop new analgesic and addiction treatment agents

Engineering Contradiction:

Improvestructural modification flexibilityVSAvoidpharmacological activity

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent changes the chemical parameters at the 3-position by introducing small, polar, neutral residues (carboxamide, thiocarboxamide) instead of the traditional phenolic hydroxyl group, and simultaneously introduces a hydroxyl group at the 4-position. This parameter change resolves the contradiction by maintaining pharmacological activity despite removing the phenolic 3-hydroxyl group, achieving both structural modification flexibility and reliability of pharmacological activity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates composite structural features by combining carboxamide or thiocarboxamide groups at the 3-position with a hydroxyl group at the 4-position. This composite approach allows the molecule to maintain opioid receptor affinity through the hydroxyl group while the carboxamide/thiocarboxamide group provides structural diversity, thus resolving the contradiction between manufacturing flexibility and pharmacological reliability

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS8680112B2Methods for treating diseases with 4-hydroxybenzomorphans

Publication Date: 2014.03.25 RENESSELAER POLYTECHNIC INST

AI summary

4-Hydroxybenzomorphans containing carboxamide or thiocarboxamide at the 3-position are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications.