FEN Lili,ФЭН Лили,GUN Baotsin,ГУН Баоцин,KARPINSKIJ Petr KH.,КАРПИНСКИЙ Петр Х.,VAJKOLE Liladkhar Murlidkhar,ВАЙКОЛЕ Лиладхар Мурлидхар
申请号：
RU2013132947/04
公开号：
RU0002599785C2
申请日:
2011.12.15
申请国别(地区):
RU
年份:
2016
代理人:
摘要：
FIELD: pharmaceutics.SUBSTANCE: invention relates to novel crystalline forms A and B of 5-chloro-N2-(2-isopropoxy-5-methyl-4-piperidin-4-yl-phenyl)-N4-[2-(propane-2-sulphonyl)-phenyl]pyrimidine-2,4-diamine, as well as to versions of method for production thereof. Crystalline forms can be used for preparing a drug for treating anaplastic lymphoma kinase mediated disorders. Such disorders include benign and malignant tumours, various types of cancer selected from anaplastic large cell lymphoma, inflammatory myofibrolastic tumour, sarcoma, lung cancer, bronchus, prostate, etc. Crystalline forms are characterised by x-ray powder diffraction indices, characteristic absorption bands of infrared radiation. Form A has according to differential scanning calorimetry melting point 174 °C, decomposition temperature higher than 250 °C and weight loss during drying equal to 0.1 % at 200 °C as defined thermogravimmetric analysis. Form B according to the differential scanning calorimetry has a melting point 162 °C, decomposition temperature higher than 250 °C and weight loss during drying equal to 0.05 % at 200 °C, established by thermogravimmetric analysis. Method of producing crystalline form involves reaction of 5-chloro-N2-(2-isopropoxy-5-methyl-4-piperidine-4-yl-phenyl)-N4-[2-(propane-2-sulphonyl)-phenyl]pyrimidine-2,4-diamine dihydrochloride with two equivalents of aqueous sodium hydroxide in a solvent acetone:water in ratio 1:1-5:1 and 1:1-1:5 (vol/vol) while heating in range of 30-70 °C, cooling to 20±3 °C with addition of water and drying in vacuum.EFFECT: crystalline forms, as demonstrated by experiments, provides 3 times higher content of substance in plasma, that is have high bioavailability as compared to salt form of compound, and have good solubility.27 cl, 6 dwg, 2 tbl, 4 exИзобретение относится к новым кристаллическим формам А и В 5-хлор-N2-(2-изопропокси-5-метил-4-пиперидин-4-ил-фенил)-N4-[2-(пропан-2-сульфонил)-фенил]пиримидин-2,4-диамина, а также к вариантам спо
