Quinoline Derivative Mesylate Crystals for Stability and Solubility
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing crystal forms of compounds used as inhibitors for TAM family kinases, CSF1R kinase, and NTRK are lacking in stability, solubility, and pharmacokinetic properties, which hinders their effectiveness in treating drug-resistant cancers and other diseases.
Innovation Solution
Development of specific crystal forms (I, II, III, and IV) of a methanesulfonate of a compound of formula (I), characterized by distinct X-ray powder diffraction patterns, through controlled precipitation methods using various solvents and temperatures, enhancing stability and solubility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing crystal forms of compound (I) are used, then the compound can inhibit TAM family kinases, CSF1R kinase, and NTRK, but the stability and solubility are insufficient
Solution Approach 1:
The patent applies parameter changes by developing multiple crystal forms (Form I, Form II, Form III, Form IV) with different X-ray powder diffraction patterns and physicochemical properties. Each crystal form has distinct stability and solubility characteristics, allowing optimization of these parameters without changing the chemical structure of the compound itself.
Solution Approach 2:
The invention utilizes phase transitions by creating different crystalline phases of the same compound. The patent describes specific preparation methods involving controlled cooling, solvent selection, and temperature conditions to induce formation of different crystal forms, thereby transitioning between phases with improved stability and solubility profiles.
2Reliability
If existing crystal forms are used, then the compound can treat diseases mediated by TAM family kinases, but the pharmacokinetic properties are insufficient
Solution Approach 1:
The patent optimizes pharmacokinetic parameters by developing crystal forms with improved stability and solubility. Form II and Form III specifically show enhanced pharmacokinetic properties compared to existing forms, leading to better therapeutic efficacy and duration of action in treating diseases mediated by TAM family kinases, CSF1R kinase, and NTRK.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The new crystal forms exhibit improved physicochemical properties, better pharmacokinetic profiles, and enhanced therapeutic efficacy against diseases mediated by TAM family kinases, CSF1R kinase, and NTRK, particularly in drug-resistant cancers.
Implementation Method 1
characterized by distinct X-ray powder diffraction patterns
Implementation Method 2
X-ray powder diffraction patterns using Cu-Kα radiation at 2θ angles
Implementation Method 3
controlled precipitation methods using various solvents and temperatures
Implementation Method 4
controlled precipitation methods
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention relates to the technical field of medicines, and in particular, to a mesylate crystalline form of a TAM family kinase and/or CSF1R kinase and/or NTRK inhibitor shown in a formula (I), a preparation method therefor and a pharmaceutical use thereof.