Analgesic Compound Formula I Reducing Hepatotoxicity

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Solution Overview

Problem

Acetaminophen-opioid combination drugs pose a risk of hepatotoxicity due to acetaminophen overdose, leading to liver failure and death, and there is a need for a less toxic alternative that does not cause gastric side effects like NSAIDs.

Innovation Solution

A compound of Formula (I) or its pharmaceutically acceptable salt is used to prepare a medicament for reducing or preventing pain and fever, which can be administered to effectively manage pain without the hepatotoxicity risks associated with acetaminophen.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If acetaminophen is used for analgesia, then pain relief is effective, but hepatotoxicity occurs due to overdose

Engineering Contradiction:

Improveanalgesic effectivenessVSAvoidhepatotoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the chemical structure of acetaminophen by replacing the phenolic hydroxyl group with various heteroaryl and aryl substituents (B1 group in Formula I), creating analogs with altered metabolic pathways that reduce NAPQI formation and subsequent liver damage while preserving analgesic activity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates composite molecular structures combining the core acetaminophen scaffold with additional heteroaryl or aryl moieties, producing compounds that maintain the desired analgesic effect while introducing metabolic stability against hepatotoxicity

Inventive Principle:

Principle #40Composite materials

2Reliability

If NSAIDs are used for pain relief, then analgesic effect is achieved, but gastric side effects occur

Engineering Contradiction:

Improveanalgesic effectivenessVSAvoidgastric upset and bleeding

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent alters the chemical parameters of traditional analgesics by introducing heteroaryl substitutions that change the drug's interaction profile with gastric tissues and inflammatory pathways, achieving pain relief through alternative mechanisms that spare the gastric mucosa

Inventive Principle:

Principle #35Parameter changes

3Reliability

If acetaminophen-opioid combination is used for enhanced analgesia, then synergistic pain relief is achieved, but hepatotoxicity risk increases

Engineering Contradiction:

Improveanalgesic effectivenessVSAvoidhepatotoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and replaces the acetaminophen component in combination drugs with structurally modified analogs that eliminate the hepatotoxic metabolic pathway while preserving the analgesic effect, allowing safe use in opioid combination formulations

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The heteroaryl-substituted compounds serve as intermediary agents that provide the desired analgesic effect without undergoing the harmful metabolic transformation to NAPQI, acting as safe replacements in combination therapies

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS10653681B2Analgesic compounds

Publication Date: 2020.05.19 KTHERA LLC

AI summary

Disclosed herein are compounds of Formula (I), methods of synthesizing compounds of Formula (I), and methods of using compounds of Formula (I) as an analgesic.