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    • 5. 发明申请
    • Synthetic process, and crystalline forms of a pyrrolotriazine compound
    • 合成方法和吡咯并三嗪化合物的结晶形式
    • US20060014741A1
    • 2006-01-19
    • US11149525
    • 2005-06-10
    • John DiMarcoJack GougoutasBharat Patel
    • John DiMarcoJack GougoutasBharat Patel
    • A61K31/5377C07D487/04
    • C07D487/04
    • The present invention provides a process for preparing pyrrolotriazine compounds of formula (I) or a pharmaceutically acceptable salt thereof. Also provided are crystalline forms of the pyrrolotriazine compound [4-[[1-(3-fluorophenyl)methyl]-1H-indazol-5-ylamino]-5-methyl-pyrrolo[2, 1-f][1,2,4]triazin-6-yl]-carbamic acid, (3S)-3-morpholinylmethyl ester and pharmaceutical compositions comprising at least one crystalline form, as well of methods of using the crystalline forms in the treatment of a proliferative disease, and methods for obtaining such crystalline forms. The compounds of formula (I), including [4-[[1-(3-fluorophenyl)methyl]-1H-indazol-5-ylamino]-5-methyl-pyrrolo[2,1-f][1,2,4]triazin-6-yl]-carbamic acid, (3S)-3-morpholinylmethyl ester, are useful for inhibiting tyrosine kinase activity of growth factor receptors such as HER1, HER2 and HER4 thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.
    • 本发明提供了制备式(I)的吡咯并三嗪化合物或其药学上可接受的盐的方法。 还提供了吡咯并三嗪化合物[4 - [[1-(3-氟苯基)甲基] -1H-吲唑-5-基氨基] -5-甲基 - 吡咯并[2,1-f] [1,2, 4]三嗪-6-基] - 氨基甲酸,(3S)-3-吗啉基甲酯和包含至少一种结晶形式的药物组合物,以及使用结晶形式治疗增殖性疾病的方法,以及用于 获得这样的结晶形式。 式(I)化合物包括[4 - [[1-(3-氟苯基)甲基] -1H-吲唑-5-基氨基] -5-甲基 - 吡咯并[2,1-f] 4]三嗪-6-基] - 氨基甲酸,(3S)-3-吗啉基甲基酯可用于抑制生长因子受体如HER1,HER2和HER4的酪氨酸激酶活性,从而使其可用作抗增殖剂,用于治疗 癌症等疾病。