Cinnamic Amide FXR Agonists With Broader Structural Diversity
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Solution Overview
Problem
Current FXR agonists, such as GW4064, require further study on structural diversity to enhance their effectiveness in managing metabolic diseases by activating FXR and regulating bile acid, lipid, and glucose metabolism.
Innovation Solution
A cinnamic amide derivative or its isomer, solvate, or pharmaceutically acceptable salt is developed to activate FXR, which is incorporated into a pharmaceutical composition for preventing, ameliorating, or treating metabolic diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current FXR agonists (e.g., GW4064) are used to activate FXR and regulate metabolism, then metabolic disease management is improved, but structural diversity and effectiveness are insufficient
Solution Approach 1:
The patent applies parameter changes by systematically modifying chemical structure parameters of FXR agonists. The invention introduces a cinnamic amide core structure with variable substituents at multiple positions (R1-R6 groups), creating a series of derivatives with different molecular weights, lipophilicities, and steric properties. This systematic parameter variation enables exploration of structure-activity relationships while maintaining FXR activation capability, thereby resolving the contradiction between reliability of FXR activation and structural diversity.
2Adaptability or versatility
If a new cinnamic amide derivative is developed to enhance structural diversity, then adaptability and effectiveness are improved, but further study and development time are required
Solution Approach 1:
The patent applies segmentation by dividing the FXR agonist molecule into distinct functional segments: a core cinnamic amide structure and multiple interchangeable substituent groups (R1-R6). This modular segmentation allows independent optimization of different molecular regions, enabling parallel synthesis of multiple derivatives with varying properties. By segmenting the molecular design, the patent accelerates the discovery process while maintaining structural diversity, thus reducing the overall development time.
Solution Approach 2:
The patent applies universality by designing a cinnamic amide core structure that serves as a universal scaffold for multiple FXR agonist derivatives. This universal scaffold can accommodate various substituent patterns while maintaining the essential FXR activation function. The multi-functional design allows a single core structure to generate numerous derivatives with different pharmacological profiles, thereby enhancing structural diversity without requiring separate development pathways for each compound class.
Data Source
AI summary
The present disclosure relates to a pharmaceutical composition containing a cinnamic amide derivative that activates FXR or an isomer, solvate, or pharmaceutically acceptable salt thereof, and a method for preparing the same.