Crystal of 1,3,5-triazine derivative or solvate thereof and method for producing same
Inventors
Kai, Hiroyuki • Murakami, Yuki
Assignees
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Publication Number
US-12312327-B2
Publication Date
2025-05-27
Expiration Date
Abstract
A crystal of a 1,3,5-triazine derivative or a solvate thereof, and a method for producing the same are provided. The present invention relates to a crystal of a compound represented by Formula (I) or a solvate thereof:and relates to a pharmaceutical composition containing the same. The present invention also relates to a crystal of a compound represented by Formula (I), or a solvate thereof.
Core Innovation
The disclosure relates to crystalline solid forms of a compound represented by Formula (I), including anhydrous crystal Form I and a dihydrate crystal. These solid forms are characterized by powder X-ray diffraction (PXRD) and Raman spectrum absorption peaks, and Form I is also described as the imino form (amino form tautomer I').
The disclosure further includes an anhydrous crystal Form II and crystallographic characterization using crystallographic parameters, including a stated space group for Form I at 298.15 K. The solid-state forms are characterized by XRPD, Raman spectroscopy, infrared absorption spectroscopy, DSC, and TG/DVS, together with general statements on acceptable measurement tolerances for the characterization methods.
The disclosure also includes a synthetic route in which Formula (VI) compounds are hydrolyzed to form compounds according to Formula (IV-B) and Formula (V), including formation of specified salts. The process further includes conversion via hydrogenolysis followed by addition of sulfuric acid to obtain Formula (I) compounds.
Claims Coverage
The consolidated claim content covers 2 inventive features directed to crystalline solid-form identification of the Formula (I) compound: anhydrous crystal Form I and a dihydrate crystal, each defined by specific PXRD characteristic peak locations, with dependent characterization by Raman spectrum absorption peaks and pharmaceutical compositions.
Anhydrous crystal form I defined by PXRD characteristic peaks
An anhydrous crystal Form I of a compound represented by Formula (I), having characteristic peaks in a powder X-ray diffraction spectrum at diffraction angles (2θ) of 15.8°±10.2°, 19.4°±10.2°, 21.7°±10.2°, 23.9°±10.2°, and 25.4°±10.2°; or diffraction angles (2θ) of 7.9°±10.2°, 9.3°±10.2°, 12.9°±10.2°, 15.8°±10.2°, and 19.4°±10.2°.
Dihydrate crystal defined by PXRD characteristic peaks
A dihydrate crystal of a compound represented by Formula (I), having characteristic peaks at diffraction angles (2θ) of 5.7°±10.2°, 7.7°±10.2°, 11.8°±10.2°, 15.2°±10.2°, and 17.7°±10.2° in a powder X-ray diffraction spectrum.
The claim set is directed to solid-form identification of the Formula (I) compound by specified PXRD characteristic peak locations for anhydrous crystal Form I and for a dihydrate crystal, with Raman spectrum absorption peak characterization and pharmaceutical compositions also described.
Stated Advantages
Form I and the dihydrate are confirmed to lack hexane residual solvent versus a residual solvent assessment against ICH Q3C PDE for hexane.
Form I has better flowability, low compressibility, and favorable fluidity.
Form I and the dihydrate are more stable, with purity and analogous substance formation under an 80°C/1 week condition for the crystalline compound.
Documented Applications
A pharmaceutical composition comprising the anhydrous crystal Form I is documented/covered.
A pharmaceutical composition comprising the dihydrate crystal is documented/covered.
The crystalline compound is described as being used for chronic cough therapy.
The crystalline compound is described as an API (active pharmaceutical ingredient).
Use as P2X3 antagonists for chronic cough.
Use as P2X2/3 antagonists for refractory chronic cough.
Therapeutic use of a P2X3 and/or P2X2/3 antagonist compound for chronic cough and refractory chronic cough.
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