Amorphous pi3k inhibitor and pharmaceutical composition comprising same
An amorphous and compositional technology, applied in drug combinations, antineoplastic drugs, pharmaceutical formulations, etc., can solve the problems of drug regulation of blood drug concentration, shortened shelf life, difficult release, etc., to achieve high solubility, high bioavailability, The effect of less side effects
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preparation Embodiment 1
[0075] Preparation Example 1. (S)-4-((1-(4,8-dichloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl) Preparation of amino)pyrido[2,3-d]pyrimidin-5(8H)-one
[0076][Formula 1] (S)-4-((1-(4,8-dichloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino ) pyrido[2,3-d]pyrimidin-5(8H)-one
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Embodiment 1
[0079] Embodiment 1. Preparation of amorphous compound
[0080] 3 g of (S)-4-((1-(4,8-dichloro-1-oxo-2-phenyl-1,2-dihydroisoquinoline-3- base)ethyl)amino)pyrido[2,3-d]pyrimidin-5(8H)-one was added to 10mL dimethyl sulfoxide (DMSO) and dissolved, then 100mL pure water (H 2 0), slowly cooled to room temperature and stirred overnight. The resulting solid was filtered and washed with 15 mL of pure water (H 2 O) washing and drying in a hot air dryer at 45° C. to obtain 2.99 g of a solid compound (yield 100%).
[0081] For this solid compound, analyzed X-ray powder diffraction (PXRD) peak and the endothermic peak of differential scanning calorimetry (DSC), its result is shown in respectively figure 1 and figure 2 .
[0082] Such as figure 1 It was confirmed that the solid compound did not have a peak at a specific value, and showed a diffuse halo-like X-ray powder diffraction analysis pattern, which is typical of an amorphous material. The product was confirmed to be amo...
experiment Embodiment 1
[0084] Experimental Example 1. Accelerated Stability Test
[0085] The solid compound powder prepared in the above example 1 is double-sealed in an LDPE bag, then sealed in an aluminum bag, left standing for 0 months and 6 months at 40 ± 2°C, RH 75 ± 5%, and then used Karl Fischer Moisture content was determined by the method, the content was determined by the HPLC method using a standard, and the impurity amount was determined by high-speed liquid chromatography (HPLC) under the following conditions. The results are shown in Table 1 below.
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[0087] -Detector: UV absorption spectrophotometer (wavelength 307nm)
[0088] - Column: Kromasil 100-5C18 (4.6 x 250 mm, 5 μm) or similar
[0089] -Column temperature: 25°C
[0090] - Injection volume: 10 μl
[0091] -Mobile phase: mobile phase A -20mmol / L ammonium acetate buffer solution (pH 4.5, acetic acid), mobile phase B-acetonitrile:methanol=8:2
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[0094] [Table 1]
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[0096] (unit...
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