Steroid Derivative FXR Agonist Structure Optimization
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Solution Overview
Problem
Current compounds fail to effectively activate mouse and human FXR, and there is uncertainty regarding the endogenous FXR ligand, limiting their therapeutic potential for FXR-related diseases.
Innovation Solution
Development of a compound represented by formula (I) or its pharmaceutically acceptable salt, which acts as an FXR agonist, specifically designed to treat FXR-related diseases by modulating FXR activity, including the use of various substituents and ring structures to enhance therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If bile acid derivatives are used as FXR ligands, then FXR activation is achieved, but therapeutic efficacy is limited due to uncertainty of endogenous ligand nature
Solution Approach 1:
The patent modifies the chemical structure of bile acid derivatives by introducing specific substituents at defined positions (R1-R6, R8-R11) to optimize FXR binding affinity and activation efficacy. This structural parameter optimization resolves the contradiction by creating compounds that reliably activate FXR while overcoming limitations of natural bile acids.
Solution Approach 2:
The invention creates composite molecular structures combining the steroid nucleus with modified side chains and aromatic substituents. These composite structures integrate beneficial properties of natural bile acids with enhanced pharmacological characteristics, achieving both reliable FXR activation and improved therapeutic versatility for treating FXR-related diseases.
2Reliability
If existing FXR ligands are used, then some FXR activity is achieved, but therapeutic potential is limited
Solution Approach 1:
The patent introduces specific substituent patterns at localized positions on the steroid nucleus (particularly R1-R6 on the aromatic ring and R8-R11 on the side chain) to enhance FXR binding. This local optimization of molecular quality creates compounds with superior FXR activation and therapeutic efficacy compared to existing ligands.
Solution Approach 2:
By systematically varying substituent types, positions, and configurations in the bile acid derivative structure, the patent optimizes both FXR activation reliability and therapeutic productivity. The modified structural parameters enable enhanced drug efficacy while maintaining reliable receptor activation.
Data Source
AI summary
The present invention relates to a compound represented by formula (I), a tautomer thereof or a pharmaceutically acceptable salt thereof, and relates to applications thereof in the preparation of drugs for treating FXR related diseases.