1,3-Disubstituted Ketene Compound for PPAR Agonism

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Solution Overview

Problem

Current treatments for non-alcoholic fatty liver disease (NAFLD) and associated conditions, such as non-alcoholic steatohepatitis (NASH), lack effective therapeutic options that target the underlying metabolic and inflammatory pathways, particularly those involving peroxisome proliferator-activated receptors (PPARs).

Innovation Solution

A novel 1,3-disubstituted ketene compound with specific structural features acts as a PPAR agonist, modulating PPARα and PPARδ activities, which can be used to treat NAFLD, NASH, and other metabolic disorders like diabetes and cardiovascular diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments are used for NAFLD and NASH, then current therapeutic options are limited, but effective targeting of underlying metabolic and inflammatory pathways is lacking

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidpathway targeting capability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The compound of formula (II) is designed to simultaneously activate multiple PPAR subtypes (PPARα, PPARγ, and/or PPARδ), enabling a single therapeutic agent to target multiple metabolic and inflammatory pathways involved in NAFLD and NASH pathogenesis, thereby overcoming the limitation of conventional single-pathway targeting approaches

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If PPAR agonists are developed to target multiple pathways, then therapeutic effectiveness improves, but compound structure complexity increases

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidcompound structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The compound of formula (II) incorporates distinct structural domains that correspond to pharmacophores for different PPAR subtypes: an aryl ketone moiety for PPARα interaction, a thiazole or oxazole ring for PPARγ binding, and additional substituents for PPARδ engagement. This segmentation allows each PPAR subtype to be targeted by a specific structural element within the overall molecule

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent merges multiple PPAR-targeting pharmacophores into a single integrated molecular framework of formula (II), combining the aryl ketone, heterocyclic ring, and substituent groups into one cohesive structure that can simultaneously interact with multiple PPAR subtypes, thereby achieving multi-pathway targeting without requiring separate compounds

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentEP3653613B11,3-di-substituted ketene compound and application thereof

Publication Date: 2022.11.16 BEBETTER MED INC

Figure 1

AI summary

Provided are a 1,3-di-substituted ketene compound having a structure as represented by formula (I) and an application thereof. Such a type of compound primarily activates peroxisome proliferator-activated receptor (PPAR) α, and also activates PPPAδ and PPPAγ. The compound may be used to treat various diseases associated with PPAR regulation and control abnormality, such as non-alcoholic fatty liver disease, and especially in treating non-alcoholic hepatitis, and may potentially be used in the treatment of diseases comprising diabetes, obesity, fibrotic diseases, cardiovascular diseases (comprising heart failure, atherosclerosis, and so on), kidney diseases (comprising chronic kidney disease, renal failure, and so on), and brain degenerative diseases (comprising Alzheimer's disease and so on), having great application value.