CDK9 Inhibitor Salt Polymorphs for Drug Stability
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Solution Overview
Problem
Existing CDK9 inhibitors lack stability and suitability for medical applications, necessitating the development of more stable forms for effective treatment of CDK9-related diseases.
Innovation Solution
The development of pharmaceutically acceptable salts and stable polymorphs of the compound 4-(((4-(5-chloro-2-(((1R,4r)-4-(((R)-1-methoxypropyl-2-yl)amino)cyclohexyl)amino)pyridin-4-yl)thiazol-2-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile, specifically maleate and fumarate forms, with defined X-ray powder diffraction, differential scanning calorimetry, and thermogravimetric analysis characteristics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing CDK9 inhibitors are used, then CDK9 inhibition activity is achieved, but stability and suitability for medical applications deteriorate
Solution Approach 1:
The patent applies parameter changes by transforming the chemical compound into different salt forms (maleate and fumarate) and crystalline polymorphs. This changes the physical and chemical parameters of the inhibitor, thereby improving its stability and suitability for medical applications while maintaining CDK9 inhibition activity
Solution Approach 2:
The patent utilizes phase transitions by developing specific polymorphic crystal forms of the CDK9 inhibitor. The different polymorphs exhibit distinct physical properties including enhanced stability, making the compound more suitable for pharmaceutical formulations and medical use
2Reliability
If polymorphs are developed to enhance stability, then stability improves, but characterization and identification complexity increases
Solution Approach 1:
The patent employs characteristic X-ray powder diffraction (XRPD) patterns as fingerprint identifiers for each polymorph. The distinct diffraction patterns serve as reliable and straightforward methods for polymorph identification and characterization, reducing the difficulty of detection despite the presence of multiple forms
Solution Approach 2:
The patent replaces complex stability testing and identification methods with standardized analytical techniques including XRPD, differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). These instrumental methods provide objective, quantitative data for polymorph characterization
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 stable polymorphs provide enhanced stability and suitability for medical use, enabling effective prevention and treatment of CDK9-related diseases such as various cancers.
Implementation Method 1
the X-ray powder diffraction pattern of the crystal form 1 comprises the diffraction angle 2θ (°) values selected from the following group: 5.48±0.2°, 14.26±0.2°, 19.68±0.2°, 22.44±0.2°
Implementation Method 2
differential scanning calorimetry, and thermogravimetric analysis characteristics
Implementation Method 3
differential scanning calorimetry, and thermogravimetric analysis characteristics
Data Source
AI summary
The present invention provides a polymorph of a CDK9 inhibitor and a preparation method for the polymorph and use thereof. Specifically, disclosed are 4-(((4-(5-chloro-2-(((1R,4r)-4-(((R)-1-methoxypropyl-2-yl)amino)cyclohexyl)amino)pyridine-4-yl)thiazole-2-yl)amino)methyl)tetrahydro-2H-pyrano-4-methylnitrile maleate or fumarate or polymorphs thereof and applications thereof. In addition, also disclosed are a pharmaceutical composition containing the substance and an application of the pharmaceutical composition.