Fused Triterpene Compounds as RORγ Modulators

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Solution Overview

Problem

Current treatments for autoimmune diseases and inflammatory disorders mediated by retinoid-related orphan receptors gamma (RORγ) and interleukin-17 (IL-17) lack effective modulators and inhibitors, which are crucial for managing conditions such as asthma, multiple sclerosis, and rheumatoid arthritis.

Innovation Solution

Development of fused triterpene compounds that act as modulators of RORγ and inhibitors of IL-17, formulated into pharmaceutical compositions to treat diseases mediated by RORγ and/or IL-17, utilizing specific structural modifications to enhance biological activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for autoimmune diseases and inflammatory disorders are used, then existing therapeutic options are available, but effective modulators and inhibitors of RORγ and IL-17 are lacking

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidavailability of RORγ modulators and IL-17 inhibitors

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent segments the therapeutic approach by developing separate compound classes: fused triterpene compounds as RORγ modulators and distinct compounds as IL-17 inhibitors. This segmentation allows targeted intervention at different points in the pathogenic pathway, addressing the lack of effective modulators and inhibitors through specialized compound designs for each specific target.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent employs parameter changes by modifying chemical structures (fused triterpene framework with various substituents) to optimize biological activity. By systematically varying structural parameters of the core triterpene skeleton, the invention generates compounds with enhanced RORγ modulatory and IL-17 inhibitory effects, thereby improving therapeutic effectiveness.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If fused triterpene compounds are developed as RORγ modulators and IL-17 inhibitors, then therapeutic potential for autoimmune and inflammatory disorders is achieved, but complexity of compound structure increases

Engineering Contradiction:

Improvetherapeutic potentialVSAvoidstructural complexity of compounds

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The fused triterpene compounds employ a nested structural approach where additional rings are fused to the core triterpene skeleton. This nesting of cyclic structures creates the necessary structural complexity for high therapeutic potential while maintaining a systematic framework that allows for rational drug design and optimization.

Inventive Principle:

Principle #7Nested doll (Nesting)

Solution Approach 2:

The compounds represent composite molecular structures combining the triterpene core with various heterocyclic and functional group substitutions. This composite approach integrates multiple structural elements that work synergistically to achieve both RORγ modulatory and IL-17 inhibitory activities, thereby enhancing therapeutic potential despite increased structural complexity.

Inventive Principle:

Principle #40Composite materials

Data Source

PatentEP3160981B1Fused triterpene compounds and uses thereof

Publication Date: 2024.01.24 PIRAMAL ENTERPRISES LTD

AI summary

The present invention discloses fused triterpene compounds, represented by the compounds of Formula I (as described herein), processes for their preparation, pharmaceutical compositions comprising the said compounds, their use as retinoid-related orphan receptors gamma (RORγ) modulators and/or interleukin-17 (IL-17) inhibitors and methods for their use in the treatment of a disease or a disorder mediated by RORγ and/or IL-17.