Nitrogenous Tricyclic Compounds as FXR Regulators
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current FXR regulators have limitations in terms of biological activity and pharmacokinetic properties, necessitating the development of novel nitrogenous tricyclic compounds that can effectively bind to the FXR nuclear receptor to treat various diseases mediated by FXR.
Innovation Solution
The development of nitrogenous tricyclic compounds, specifically those adhering to Formula (I), which act as regulators by binding to the FXR (or NR1H4) receptor, offering improved bioactivity and pharmacokinetic properties, and are used in pharmaceutical compositions to treat diseases such as cardiovascular diseases, obesity, and liver-related disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If known FXR regulators are used, then FXR-mediated diseases can be treated, but biological activity and pharmacokinetic properties are insufficient
Solution Approach 1:
The patent applies parameter changes by modifying molecular structure parameters of FXR regulators. Specifically, the invention introduces nitrogenous tricyclic core structures with varying substituents (R1, R2, R3, R4, R5, R6 groups) to optimize biological activity and pharmacokinetic properties. The systematic variation of chemical parameters including ring structures, substituent types, and molecular weight ranges enables improvement of drug performance while managing structural complexity
Solution Approach 2:
The patent employs composite materials principles by creating hybrid molecular structures that combine different functional groups and ring systems. The nitrogenous tricyclic compounds integrate aromatic rings, heterocyclic moieties, and various substituents (such as fluorinated groups, hydroxyl groups, and alkyl chains) into unified molecular architectures, achieving synergistic effects that enhance both biological activity and pharmacokinetic properties
2Adaptability or versatility
If FXR regulators are developed to treat multiple diseases, then therapeutic versatility improves, but development complexity increases
Solution Approach 1:
The patent implements universality by designing nitrogenous tricyclic compounds with broad therapeutic applicability. The core molecular structure (Formula I) serves as a universal scaffold that can regulate FXR activity across multiple disease contexts including cardiovascular diseases, metabolic disorders, inflammatory conditions, and liver diseases. This multi-functional design allows a single compound class to address diverse FXR-mediated pathologies without requiring separate development programs for each indication
Data Source
AI summary
The present invention relates to nitrogenous tricyclic compounds and uses thereof in medicine, in particular, the present invention discloses a novel nitrogenous tricyclic compound used as an FXR active regulator and a stereoisomer, a geometrical isomer, a tautomer, a N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and use of the compound in the manufacture of a drug for treating a disease and/or disorder regulated by FXR. The present invention further discloses a pharmacetically acceptable composition containing the compound and a method of treating a disease and/or disorder mediated by FXR comprising administering the compound or pharmaceutical composition thereof disclosed herein.