GPR84 Antagonists for Multiple Sclerosis Treatment

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Solution Overview

Problem

Current therapies for multiple sclerosis lack effective antagonists for GPR84, a receptor involved in inflammatory and neuro-inflammatory processes, which contributes to the progression of the disease.

Innovation Solution

Development of novel compounds with a specific formula that antagonize GPR84, potentially used in pharmaceutical compositions to treat multiple sclerosis, by inhibiting its activity and reducing inflammatory responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapies for multiple sclerosis are used, then treatment is provided, but effective antagonists for GPR84 are lacking, limiting therapeutic effectiveness

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidreceptor targeting capability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

Instead of using agonists or other modulators, the invention employs antagonists that block GPR84 receptor activity. This inverted approach of blocking rather than activating the receptor provides novel therapeutic effectiveness for multiple sclerosis by preventing inflammatory signaling through GPR84.

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The invention modifies the chemical parameters of GPR84 ligands by developing compounds with specific molecular structures (Formula I with various substituents R1-R6) that exhibit antagonist activity. By changing structural parameters such as aromatic rings, heteroatoms, and substituent groups, the compounds achieve effective GPR84 antagonism with improved therapeutic properties.

Inventive Principle:

Principle #35Parameter changes

2Object-affected harmful factors

If GPR84 activity is not inhibited, then inflammatory processes continue, but disease progression occurs

Engineering Contradiction:

Improveinflammatory responseVSAvoiddisease progression timeline

Core Design Contradiction:

Object-affected harmful factorsVSDuration of action of stationary object

Solution Approach 1:

The GPR84 antagonists exert preliminary anti-action by blocking the receptor before inflammatory signaling can occur. By pre-emptively inhibiting GPR84 activity, the compounds prevent the initiation of inflammatory cascades that would otherwise contribute to multiple sclerosis pathology and disease progression.

Inventive Principle:

Principle #9Preliminary anti-action

Solution Approach 2:

The invention converts the harmful inflammatory signaling through GPR84 into a beneficial therapeutic effect. By targeting and blocking the receptor that mediates harmful inflammation, the antagonists transform the pathological GPR84 pathway into a therapeutic opportunity, reducing neuroinflammation and potentially slowing disease progression.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentEP3378862B1Dihydropyrimidinoisoquinolinones and pharmaceutical compositions thereof for the treatment of multiple sclerosis

Publication Date: 2022.03.16 GALAPAGOS NV

AI summary

A compound according to Formula la: wherein L1, G, and R1 are as decribed herein. The present invention relates to novel compounds according to Formula I that antagonize GPR84, a G-protein-coupled receptor that is involved in inflammatory conditions, and methods for the production of these novel compounds, pharmaceutical compositions comprising these compounds, and methods for the prevention and/or treatment of inflammatory conditions (for example inflammatory bowel diseases (IBD), rheumatoid arthritis, vasculitis, lung diseases (e.g. chronic obstructive pulmonary disease (COPD) and lung interstitial diseases (e.g. idiopathic pulmonary fibrosis (IPF))), neuroinflammatory conditions, infectious diseases, autoimmune diseases, endocrine and/or metabolic diseases, and/or diseases involving impairment of immune cell functions by administering a compound of the invention.