Deuterated HDAC Inhibitors for Subtype Selectivity and Stability

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Solution Overview

Problem

Current HDAC inhibitors lack selectivity towards specific subtypes, limiting their effectiveness in enhancing tumor immune synergy and metabolic stability, and there is a need for improved combinations with PD-1 and VEGF inhibitors to enhance anti-tumor efficacy.

Innovation Solution

Development of a class of unique HDAC inhibitors with selectivity towards specific subtypes, combined with PD-1 and VEGF inhibitors, to enhance tumor immune synergy and metabolic stability, leading to remarkable synergistic effects in tumor regression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current HDAC inhibitors are used, then they can inhibit tumor cell growth, but they lack selectivity towards specific subtypes and have limited metabolic stability

Engineering Contradiction:

Improveselectivity towards specific HDAC subtypesVSAvoideffectiveness in enhancing tumor immune synergy

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces deuterium atoms at specific positions (X1-X15) of the HDAC inhibitor molecule to create localized modifications. This selective deuteration enhances metabolic stability and selectivity for specific HDAC subtypes without altering the overall molecular structure, thereby improving reliability while maintaining adaptability for tumor immune synergy.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent changes the isotopic parameter of hydrogen to deuterium at specific positions in the molecule. This parameter change increases metabolic stability and enhances selectivity for specific HDAC subtypes, resolving the contradiction between reliability and adaptability by improving both selectivity and therapeutic effectiveness simultaneously.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If HDAC inhibitors are used alone, then they can inhibit tumor cell growth, but they have limited anti-tumor efficacy compared to combination therapy

Engineering Contradiction:

Improveanti-tumor efficacyVSAvoidcombination therapy regimen

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent designs HDAC inhibitors with pre-optimized deuterium substitution patterns that enhance metabolic stability and selectivity before administration. This preliminary structural optimization ensures that the compound achieves maximum anti-tumor efficacy when used in combination therapy, reducing the complexity of regimen design while improving productivity.

Inventive Principle:

Principle #10Preliminary action

3Reliability

If deuterium substitution is introduced to enhance metabolic stability, then the compound structure becomes more complex, but this may affect synthesis difficulty

Engineering Contradiction:

Improvemetabolic stabilityVSAvoidsynthesis difficulty

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent divides the HDAC inhibitor molecule into specific positions (X1-X15) where deuterium substitution can be independently introduced. This segmentation allows for systematic optimization of metabolic stability at key positions without requiring complete deuteration of the molecule, thereby maintaining ease of manufacture while improving reliability.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentEP4631931A1HDAC inhibitor and use thereof

Publication Date: 2025.10.15 WIGEN BIOMEDICINE TECH (SHANGHAI) CO LTD

AI summary

An HDAC inhibitor and the use thereof. Specifically, the present invention relates to a compound as represented by general formula (1) and a preparation method therefor, and the use of the compound of general formula (1) and each isomer, each crystal form, a pharmaceutically acceptable salt, hydrate or solvate thereof as an HDAC inhibitor in the preparation of an anti-tumor drug.