Selective HDAC6 Inhibitor Composition for Lower-Toxicity Therapy

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Solution Overview

Problem

Current HDAC inhibitors, particularly non-selective ones, cause side effects such as fatigue and nausea due to the inhibition of class I HDACs, limiting their use in treating diseases like cancer, inflammatory diseases, autoimmune diseases, and neurological disorders, while selective HDAC6 inhibitors with improved bioavailability and reduced toxicity are needed.

Innovation Solution

Development of an oxadiazole derivative compound with selective HDAC6 inhibitory activity, represented by Chemical Formula I, and its stereoisomers or pharmaceutically acceptable salts, which can be used to inhibit HDAC6 activity-related diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If non-selective HDAC inhibitors are used to treat diseases, then anti-cancer activity is achieved, but side effects such as fatigue and nausea occur due to inhibition of class I HDACs

Engineering Contradiction:

Improveanti-cancer activityVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention segments the HDAC inhibitor market by developing selective inhibitors for specific HDAC isoforms (HDAC1, HDAC2, HDAC3, HDAC6, HDAC8) rather than using non-selective inhibitors. This allows targeted inhibition of specific HDAC enzymes responsible for cancer-related pathways while avoiding inhibition of class I HDACs that cause side effects like fatigue and nausea.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies local quality by designing inhibitors with specific molecular structures tailored to bind selectively to particular HDAC isoforms. Different chemical structures are optimized for different HDAC targets, allowing the inhibitor to have high affinity for the desired HDAC isoform while having minimal interaction with other HDAC enzymes, thereby achieving selective therapeutic action.

Inventive Principle:

Principle #3Local quality

2Object-affected harmful factors

If selective HDAC6 inhibitors are developed, then side effects caused by non-selective inhibition are reduced, but bioavailability and toxicity issues remain to be addressed

Engineering Contradiction:

Improvetoxicity reductionVSAvoidbioavailability

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The invention employs parameter changes by systematically modifying chemical parameters of the inhibitor molecules, including substituent groups, molecular weight, lipophilicity, and structural flexibility. These parameter optimizations are designed to improve pharmacokinetic properties such as oral bioavailability, tissue penetration, and metabolic stability while maintaining selective HDAC6 inhibition and reducing toxicity.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS12570646B2Compounds as histone deacetylase 6 inhibitor, and pharmaceutical composition comprising the same

Publication Date: 2026.03.10 CHONG KUN DANG PHARMACEUTICAL CORP

AI summary

The present invention relates to a novel compound having a selective HDAC6 inhibitory activity, stereoisomers thereof, pharmaceutically acceptable salts thereof, a use thereof in preparation of a therapeutic medicament, a pharmaceutical composition containing the same, a therapeutic method using the composition, and a method for preparing the same, wherein the novel compound having the selective HDAC6 inhibitory activity is represented by chemical formula (I) below.