Fused Pentacyclic Imidazole Derivatives for TNFα Modulation

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Solution Overview

Problem

Current pharmacological agents modulating TNFα activity are primarily macromolecular and limited in structural diversity, which restricts their therapeutic applications and efficacy across various inflammatory, autoimmune, neurological, and oncological disorders.

Innovation Solution

Development of fused pentacyclic imidazole derivatives that act as potent modulators of TNFα signaling, offering a new structural class with diverse pharmacological profiles for treating inflammatory, autoimmune, neurological, and oncological disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If macromolecular TNFα inhibitors (antibodies, fusion proteins) are used, then TNFα activity is inhibited, but structural diversity is limited and therapeutic applications are restricted

Engineering Contradiction:

ImproveTNFα inhibition efficacyVSAvoidstructural diversity and therapeutic application range

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the fundamental parameter of molecular size and structural class from macromolecular (antibodies, fusion proteins) to small molecule fused pentacyclic imidazole derivatives. This parameter change enables diverse chemical structures within the small molecule class, allowing adaptation to different TNFα-related targets and disease indications while maintaining potent inhibitory activity through optimized molecular interactions

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates composite chemical structures by fusing multiple rings (imidazole core with additional cyclic structures) to form pentacyclic frameworks. This composite structural approach generates diverse molecular architectures with varying pharmacological profiles, enabling broad therapeutic applications across inflammatory, autoimmune, neurological, and oncological disorders

Inventive Principle:

Principle #40Composite materials

2Reliability

If currently approved macromolecular products are used, then treatment of inflammatory and autoimmune disorders is achieved, but efficacy across other disorder types (neurological, oncological, etc.) is limited

Engineering Contradiction:

Improvetreatment efficacy for inflammatory and autoimmune disordersVSAvoidtherapeutic spectrum across different disorder types

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The fused pentacyclic imidazole derivative platform achieves multi-functionality by targeting different TNFα-related pathways and receptors. The small molecule structure can interact with multiple biological targets (TNFα itself, TNF receptors, downstream signaling molecules), enabling treatment of diverse disease types including inflammatory, autoimmune, neurological, cardiovascular, metabolic, ocular, and oncological disorders from a single chemical platform

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentEP3596078B1Fused pentacyclic imidazole derivatives as modulators of TNF activity

Publication Date: 2023.04.12 UCB BIOPHARMA SPRL

AI summary

A series of substituted fused pentacyclic imidazopyridine and imidazopyridazine derivatives, and analogues thereof, being potent modulators of human TNFα activiy, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.