Crystalline forms of (S)-1-(4-fluorophenyl)-1-(2-(4-(6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1- f][1,2,4]triazin-4-yl)piperazinyl)-pyrimidin-5-yl)ethan-1-amine and methods of making
Inventors
Waetzig, Joshua D. • Wilkie, Gordon
Assignees
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Publication Number
US-11964980-B2
Publication Date
2024-04-23
Expiration Date
Abstract
Crystalline Forms of Compound (I): pharmaceutically acceptable salts thereof and solvates of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating disorders and conditions associated with oncogenic KIT and PDGFRA alterations using the same, and methods for making Compound (I) and crystalline forms thereof are also disclosed.
Core Innovation
The invention relates to characterization and preparation of crystalline forms of Compound (I). Crystalline Form A is characterized by an X-ray powder diffractogram comprising at least three peaks at 2θ angles chosen from 11.5±0.2, 15.4±0.2, 16.7±0.2, 20.0±0.2, and 21.6±0.2. Dependent claims further refine the number and selection of diffraction peaks and add DSC thermogram endothermic event temperature constraints.
The document also characterizes other crystalline forms and salts associated with Compound (I), including crystalline Form O, crystalline Form T tosylate, crystalline Form Tr tartrate salt, and crystalline Form H hydrochloride. These forms are supported by XRD 2θ tables, DSC data, 13C NMR shifts, TGA-related notes, solubility in simulated intestinal fluid and simulated gastric fluid, and dynamic vapor sorption behavior.
Claims Coverage
The claims define crystalline Form A of Compound (I) by an X-ray powder diffractogram with specified peak positions. Dependent claims further tighten the diffraction peak count and specific 2θ peak positions, add DSC thermogram endothermic event temperature constraints, and recite a pharmaceutical composition comprising the crystalline Form A with pharmaceutically acceptable excipients.
X-ray powder diffractogram peak set for crystalline Form A
Crystalline Form A of Compound (I) is characterized by an X-ray powder diffractogram which comprises at least three peaks at 2θ angles chosen from 11.5±0.2, 15.4±0.2, 16.7±0.2, 20.0±0.2, and 21.6±0.2.
Minimum number of crystalline Form A diffraction peaks
Crystalline Form A is characterized by an X-ray powder diffractogram comprising at least seven peaks at selected 2θ angles from the specified list.
Specific crystalline Form A 2θ peak subset
Crystalline Form A is characterized by an X-ray powder diffractogram with peaks at 2θ angles 11.5±0.2, 15.4±0.2, 16.7±0.2, 20.0±0.2, and 21.6±0.2.
DSC thermogram endothermic temperature constraint for crystalline Form A
Crystalline Form A is characterized by a DSC thermogram having an endothermic event with a signal at a temperature ranging from 194°C to 195°C or an onset temperature of 193°C.
Pharmaceutical composition comprising crystalline Form A
A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and the crystalline Form A of Compound (I).
The claims cover crystalline Form A of Compound (I) defined by X-ray powder diffractogram peak patterns at specified 2θ values, with dependent claims increasing the minimum peak count, specifying particular peak subsets, adding DSC endothermic event temperature/onset constraints, and extending the definition to a pharmaceutical composition containing pharmaceutically acceptable excipients.
Stated Advantages
Improving solid-state stability.
Providing substantially pure APIs.
Documented Applications
Treating oncogenic KIT/PDGFRA-alteration disorders using Compound (I) as selective inhibitors of KIT and/or PDGFRα, including mastocytosis and GIST.
Clinical relevance is described with ISM/SSM dosing and outcomes, supported by KIT D816V allele fraction-related biomarker graphs.
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