Piperidine Derivative FLT3 Inhibition for AML Relapse

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Solution Overview

Problem

Current treatments for acute myeloid leukemia (AML) are ineffective against mutant FLT3 and often result in relapse due to the expression of mutant FLT3 and wild-type FLT3, necessitating the development of new drugs that target both forms of the receptor.

Innovation Solution

A piperidine derivative compound with specific structural features, its stereoisomers, or pharmaceutically acceptable salts are developed to inhibit FLT3 activity, offering therapeutic potential for FLT3-related diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional FLT3 inhibitors are used to treat AML, then wild-type FLT3 activity is suppressed, but mutant FLT3 expression reduces drug effectiveness and leads to relapse

Engineering Contradiction:

Improvedrug effectivenessVSAvoidtarget coverage

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The piperidine derivative compound is designed to simultaneously inhibit both wild-type FLT3 and mutant FLT3 (including FLT3-ITD and FLT3-TKD) through a single molecular structure. This universal inhibitor approach allows one drug to target multiple forms of the FLT3 receptor, resolving the contradiction between drug effectiveness and target coverage by making the drug effective across all FLT3 variants rather than requiring separate inhibitors for each type.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If standard chemotherapy is used for AML treatment, then initial response may be achieved, but frequent relapse occurs due to persistent mutant FLT3 expression

Engineering Contradiction:

Improvetreatment responseVSAvoidremission duration

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The piperidine derivative provides continuous inhibition of FLT3 signaling pathways, preventing the transient or intermittent effect of conventional chemotherapy. By maintaining sustained suppression of both wild-type and mutant FLT3 activity throughout the treatment course and during remission, the drug ensures continuous useful action that prevents disease resurgence and extends remission duration, directly addressing the relapse issue.

Inventive Principle:

Principle #20Continuity of useful action

3Reliability

If conventional drugs target FLT3, then some inhibition is achieved, but mutant FLT3 expression creates drug resistance and poor prognosis

Engineering Contradiction:

ImproveprognosisVSAvoiddrug resistance

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The piperidine derivative introduces structural parameter changes compared to conventional FLT3 inhibitors, specifically incorporating a piperidine ring with specific substituents (X, Y, Z groups) that alter the binding characteristics. This structural modification enables the drug to effectively bind to and inhibit both wild-type and mutant FLT3 receptors with different binding affinities, thereby overcoming drug resistance mechanisms that arise from mutant FLT3 expression and improving patient prognosis.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP4620950A1Piperidine derivative, salt of same, and pharmaceutical composition containing same as active ingredient

Publication Date: 2025.09.24 PHARMCADD CO LTD

AI summary

The present invention relates to a piperidine derivative compound and a use thereof. The piperidine derivative compound of the present invention exhibits excellent inhibitory activity against FLT3, and thus can be usefully employed in the treatment or prevention of FLT3-related diseases.