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PYRIDIN SUBSTITUERET 2-AMINOPYRIDIN PROTEINKINASE-INHIBITORKRYSTAL

机译:吡啶取代和2-氨基吡啶蛋白质中国抑制剂晶体

摘要

The present invention discloses a crystal of citrate salt of pyridine-substituted 2-aminopyridine-based protein kinase inhibitors, in particular, to crystal of 5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-4'-methoxy-6'-((S)-2-methylpiperazin -1-yl)-3,3'-bipyridin-6-amine citrate salt, a method for preparation thereof, a crystalline composition and a pharmaceutical composition comprising the crystal, and further discloses the use of crystals of citrate salt of the compound of Formula I in protein kinase-related diseases. The crystals of citrate salt according to the present invention are superior to 5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-4'-methoxy-6'-((S)-2-methylpiperazin-1-yl)-3,3'-bipyridin-6-amine or other salts of 5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-4'-methoxy-6'-((S)-2-methylpiperazin-1-yl)-3,3'-bipyridin-6-amine in at least one aspect of bioavailability, hygroscopicity, stability, solubility, purity, ease of preparation, and the like.
机译:本发明公开了基于吡啶取代的2-氨基吡啶的蛋白激酶抑制剂的柠檬酸盐的晶体,特别是5-((R)-1-(2,6-二氯-3-氟苯基)乙氧基的晶体)。 -4'-甲氧基-6'-((S)-2-甲基哌嗪-1-基)-3,3'-联吡啶-6-柠檬酸柠檬酸盐,其制备方法,结晶组合物和药物组合物,包括该晶体,并进一步公开了式I化合物的柠檬酸盐晶体在蛋白激酶相关疾病中的用途。根据本发明的柠檬酸盐的晶体优于5-((R)-1-(2,6-二氯-3-氟苯基)乙氧基)-4'-甲氧基-6'-((S)-2 -甲基哌嗪-1-基)-3,3'-联吡啶-6-胺或5-((R)-1-(2,6-二氯-3-氟苯基)乙氧基)-4'-甲氧基的其他盐生物利用度,吸湿性,稳定性,溶解性,纯度,易于制备等方面的至少一方面中的6'-(((S)-2-甲基哌嗪-1-基)-3,3'-联吡啶-6-胺) 。

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