FXR Agonist Compounds With Improved ADME and Lower Side Effects

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing FXR agonists lack excellent physicochemical, in vitro and/or in vivo ADME properties and pharmacokinetics, and are associated with significant side effects.

Innovation Solution

Development of novel compounds with specific structural features, such as the formula (I), which are synthesized through routes A, B, C, or D, to enhance ADME properties and reduce side effects, and are used as FXR agonists.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing FXR agonists are used to treat FXR-mediated diseases, then therapeutic effect is achieved, but side effects are significant and ADME properties are poor

Engineering Contradiction:

Improvetherapeutic effectVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by systematically modifying the chemical structure of FXR agonists through varying substituents (R1-R6, R0) at different positions of the core molecular framework. This includes changing molecular weight, lipophilicity, and other physicochemical parameters to optimize both therapeutic efficacy and reduce side effects while improving ADME properties

Inventive Principle:

Principle #35Parameter changes

2Reliability

If existing FXR agonists are used to treat FXR-mediated diseases, then therapeutic effect is achieved, but ADME properties are poor

Engineering Contradiction:

Improvetherapeutic effectVSAvoidADME properties

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent systematically modifies molecular parameters including substituent types (halogen, alkyl, alkoxy groups), their positions, and combinations to optimize absorption, distribution, metabolism, and excretion properties while maintaining therapeutic efficacy

Inventive Principle:

Principle #35Parameter changes

3Reliability

If novel compounds with optimized structure are developed to improve ADME properties and reduce side effects, then pharmacological properties are improved, but compound structure complexity increases

Engineering Contradiction:

Improvepharmacological propertiesVSAvoidcompound structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the FXR agonist molecule into distinct functional regions: a core structure (naphthalene or indole ring) and multiple substitutable positions (R1-R6, R0) that can be independently optimized. This modular approach allows systematic improvement of pharmacological properties without completely redesigning the entire molecule

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent employs a universal core structure that can accommodate various substituents, creating a platform where a single molecular framework serves multiple therapeutic purposes and can be adapted to optimize different pharmacological properties through substituent variation

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS12600716B2Compounds for modulating activity of FXR and uses thereof

Publication Date: 2026.04.14 GANNEX PHARMA CO LTD

AI summary

Provided are a compound for modulating the activity of FXR having a structure of formula (I), a pharmaceutically acceptable salt, an ester or a stereoisomer thereof.