Thiophene Compounds for Selective Anti-cancer Activity

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Solution Overview

Problem

There is a need for highly selective and active anti-proliferative compounds to effectively treat hyperproliferative disorders such as cancer, particularly T-cell lymphoma, hepatoma, and prostate cancer, as existing compounds lack selectivity and efficacy.

Innovation Solution

Development of specific combinations of substituents in 2-amino, 3-carboxylic ester thiophenes and their derivatives, which exhibit significant and selective anticancer activity, formulated into pharmaceutical compositions for use as medicines.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing anti-proliferative compounds are used, then some cytostatic activity is achieved, but selectivity against specific cancer types is insufficient

Engineering Contradiction:
ImproveselectivityVSAvoidbroad applicability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by introducing specific substituent patterns at defined positions on the thiophene core structure. Different substituents (R1-R6) are placed at specific locations to create compounds with tailored selectivity for different cancer types, while maintaining the core anti-proliferative mechanism.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent employs parameter changes by systematically varying substituent types, positions, and combinations on the thiophene ring. This includes changing electronic properties, steric effects, and hydrophobicity parameters through different substituent groups to optimize both selectivity and broad applicability across cancer types.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If existing anti-proliferative compounds are used, then general cytostatic activity is achieved, but efficacy against specific cancer types (T-cell lymphoma, hepatoma, prostate cancer) is insufficient

Engineering Contradiction:
ImproveefficacyVSAvoidanti-proliferative activity
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent applies segmentation by dividing the molecule into a core thiophene structure and multiple substituent regions (R1-R6). This allows independent optimization of different molecular regions to achieve both high efficacy against specific cancers and maintained broad anti-proliferative activity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses composite materials by combining the thiophene core with diverse substituent groups including aromatic rings, heterocycles, alkyl chains, and functional groups. This composite structure creates compounds with enhanced efficacy while preserving broad-spectrum anti-proliferative properties.

Inventive Principle:
Principle #40Composite materials

Data Source

PatentEP2864312B1Novel Anti-cancer thiophene compounds
Publication Date: 2021.09.22 KATHOLIEKE UNIV LEUVEN
  • EP2864312B1 patent drawingFigure 1A
  • EP2864312B1 patent drawingFigure 1B
  • EP2864312B1 patent drawingFigure 1C

AI summary

The present invention relates to compounds having cytostatic activity against tumor cells. The compounds of the invention are of formula (I), or derivatives hereof, wherein R0, R1, R2, A, and X have defined meanings as described in claim 1.