Nitrogen-Containing Tricyclic Crystal Form for FXR Drug Stability

Solution Overview

Problem

Existing nitrogen-containing tricyclic compounds, such as 2-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)-10H-spiro[benzo[6,7]oxepino[3,2-b]pyridine-11,1′-cyclopropane]-7-carboxylic acid, lack specific crystal forms, which can affect drug quality, stability, solubility, and bioavailability, hindering their effective use as FXR modulators for treating various diseases.

Innovation Solution

Development of a novel crystal form A of the compound, characterized by specific X-ray powder diffraction peaks and thermal properties, enhancing stability and pharmacokinetic properties, suitable for pharmaceutical use.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a nitrogen-containing tricyclic compound is used as an FXR modulator, then therapeutic effect is achieved, but drug quality and stability are compromised due to lack of specific crystal form

Engineering Contradiction:

Improvedrug qualityVSAvoidcompound stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by transforming the compound from an amorphous or undefined crystal state to a specific crystalline form (Form A). This phase transition from disordered to ordered structure fundamentally changes the physical and chemical parameters of the compound, resulting in improved stability, solubility, and bioavailability while maintaining therapeutic efficacy.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention utilizes phase transitions by establishing a specific crystal form of the nitrogen-containing tricyclic compound. The transition from an undefined solid state to a well-defined crystalline structure (Form A) with specific X-ray diffraction patterns and thermal properties enhances the compound's pharmaceutical properties including stability, solubility, and bioavailability.

Inventive Principle:

Principle #36Phase transitions

2Reliability

If a nitrogen-containing tricyclic compound is used as an FXR modulator, then therapeutic effect is achieved, but solubility and bioavailability are reduced due to lack of specific crystal form

Engineering Contradiction:

Improvetherapeutic effectVSAvoidsolubility

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent applies parameter changes by transforming the compound from an amorphous or undefined crystal state to a specific crystalline form (Form A). This phase transition from disordered to ordered structure fundamentally changes the physical and chemical parameters of the compound, resulting in improved stability, solubility, and bioavailability while maintaining therapeutic efficacy.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention utilizes phase transitions by establishing a specific crystal form of the nitrogen-containing tricyclic compound. The transition from an undefined solid state to a well-defined crystalline structure (Form A) with specific X-ray diffraction patterns and thermal properties enhances the compound's pharmaceutical properties including stability, solubility, and bioavailability.

Inventive Principle:

Principle #36Phase transitions

Data Source

PatentUS12492211B2Crystalline form of nitrogen-containing tricyclic compound and use thereof

Publication Date: 2025.12.09 SUNSHINE LAKE PHARMA CO LTD

AI summary

A crystalline form A of a nitrogen-containing tricyclic compound shown in formula (I), a pharmaceutical composition containing the crystalline form A, and the use of the crystalline form A or the pharmaceutical composition in the preparation of a medication for preventing, treating or relieving an FXR-mediated disease of a patient.