Small Molecule TNFα Inhibitors for Cytokine Diseases

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Solution Overview

Problem

Current treatments for chronic inflammatory diseases mediated by cytokines, such as rheumatoid arthritis, face limitations due to limited tissue penetration, high production costs, immunogenicity, treatment resistance, and increased risk of opportunistic infections with existing biotherapies and small molecule inhibitors.

Innovation Solution

Development of newly synthesized compounds with cytokine-inhibitory activity, specifically a compound of formula (I) that can be used alone or in combination with other active substances for diagnostic, preventive, or therapeutic purposes in cytokine-mediated diseases, offering an alternative therapeutic strategy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If anti-TNFα antibodies (infliximab, golimumab) are used to treat chronic inflammatory diseases, then cytokine activity is neutralized and inflammatory symptoms are alleviated, but tissue penetration is limited, production cost is high, and risk of opportunistic infections increases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidlimited tissue penetration, high production cost, immunogenicity, treatment resistance, increased risk of opportunistic infections

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the molecular parameters from large biologic molecules (antibodies) to small molecule compounds (formula I), altering key properties including tissue penetration capability, production cost structure, and immunogenicity profile. This parameter transformation enables the compound to overcome the limitations of existing anti-TNFα therapies while maintaining therapeutic efficacy.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If small molecule inhibitors (SPD304) are used to prevent TNFα binding to TNFR1, then inflammatory response is inhibited, but potential toxicity increases

Engineering Contradiction:

Improveinflammatory response inhibitionVSAvoidpotential toxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by designing the small molecule compound (formula I) with specific structural characteristics that enable selective interaction with TNFα. The molecular structure includes specific functional groups and spatial arrangement that confer selectivity, allowing the compound to inhibit TNFα binding while minimizing off-target effects and toxicity associated with non-selective small molecule inhibitors.

Inventive Principle:

Principle #3Local quality

3Reliability

If biotherapies are administered subcutaneously or intravenously, then cytokine activity is inhibited, but administration complexity and treatment cost increase

Engineering Contradiction:

Improvecytokine inhibitionVSAvoidadministration route complexity

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent substitutes the mechanical/administrative complexity of parenteral administration (subcutaneous or intravenous injection) with oral administration capability. The small molecule compound (formula I) is designed with pharmacokinetic properties that enable absorption through the gastrointestinal tract, replacing the need for complex injection systems and specialized administration procedures.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS20230416239A1Compounds and methods for treating a cytokine-mediated disease

Publication Date: 2023.12.28 PEPTINOV SAS

AI summary

The present invention relates to a compound of the following formula (I):in particular for use use in the diagnostic, prevention or treatment of a cytokine-mediated disease in an individual.