Fluorophenyl beta-hydroxyethylamines for selective glucose uptake

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Solution Overview

Problem

Current treatments for hyperglycaemia, particularly in conditions like type 2 diabetes and severe insulin resistance, are not sufficiently effective and often come with undesirable side effects.

Innovation Solution

Development of certain fluoro-substituted β-hydroxyethylamines that act as agonists at the β2-adrenergic receptor, increasing glucose uptake in skeletal muscle without significant cAMP release, thereby reducing common side effects associated with traditional β2-adrenergic agonists.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional β2-adrenergic agonists are used to increase glucose uptake, then glucose uptake in skeletal muscle is improved, but significant cAMP release causes harmful side effects

Engineering Contradiction:

Improveglucose uptakeVSAvoidcAMP release side effects

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent modifies the chemical structure of β2-adrenergic agonists by introducing specific fluorophenyl and hydroxyethylamine groups, which changes the pharmacological parameters of the compound. This structural modification allows the compound to activate the β2-adrenergic receptor while minimizing cAMP release, thereby resolving the contradiction between effective glucose uptake and harmful side effects

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention introduces specific functional groups (fluorophenyl and hydroxyethylamine) at particular positions in the molecule to create localized structural features that selectively modulate receptor interaction. This local structural optimization enables the compound to achieve beneficial glucose uptake effects while avoiding the harmful cAMP-mediated side effects

Inventive Principle:

Principle #3Local quality

2Productivity

If current standard treatments (metformin or insulin supplement) are used for severe insulin resistance, then glucose homeostasis is partially improved, but treatment effectiveness is insufficient

Engineering Contradiction:

Improveglucose homeostasis controlVSAvoidtreatment effectiveness

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent employs β2-adrenergic receptor activation as an intermediary mechanism to improve glucose homeostasis in severe insulin resistance. Instead of directly targeting the insulin pathway (which is dysfunctional in SIR), the invention uses adrenergic signaling as an alternative mediator to stimulate glucose uptake in skeletal muscle, bypassing the defective insulin receptor pathway

Inventive Principle:

Principle #24Intermediary (Mediator)

3Ease of operation

If conventional diabetes treatments are used, then some glucose regulation is achieved, but multiple side effects occur including downregulation of insulin pathway

Engineering Contradiction:

Improveglucose regulationVSAvoidinsulin pathway downregulation

Core Design Contradiction:

Ease of operationVSObject-generated harmful factors

Solution Approach 1:

The patent inverts the conventional approach to diabetes treatment by not targeting the insulin pathway directly, but rather using the adrenergic system to achieve glucose regulation. This inverse strategy avoids the harmful downregulation and desensitization of the insulin pathway that occurs with conventional treatments, while still achieving effective glucose control

Inventive Principle:

Principle #13The other way round (Inversion)

Data Source

PatentUS12280023B2Fluorophenyl beta-hydroxyethylamines and their use in the treatment of hyperglycaemia

Publication Date: 2025.04.22 ATROGI

AI summary

There is herein provided a compound of formula (I).