| 摘要 |
The present invention relates to 3-(1-{3-[5-(1-methyl-piperidin-4-ylmethoxy)-pyrimidin-2-yl]-benzyl}-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzonitrile hydrochloride solvates and crystalline modifications thereof. The present invention further relates to processes of manufacturing these crystalline modifications as well as their use in the treatment and/or prophylaxis of physiological and/or pathophysiological conditions, which are caused, mediated and/or propagated by the inhibition, regulation and/or modulation of signal transduction of kinases, in particular by the inhibition of tyrosine kinases, e.g. pathophysiological conditions such as cancer. |
| 代理机构 |
Millen, White, Zelano, Branigan, P.C. |
代理人 |
Millen, White, Zelano, Branigan, P.C. |
| 主权项 |
1. A method for the treatment of kidney cancer, kidney cell carcinoma, lung cancer, lung adenocarcinoma, small cell lung carcinoma, or bronchial carcinoma, which in each case is caused, mediated, or propagated by Met-kinase, said method comprising administering to a patient an effective amount of a compound selected from the following compounds:
(a) a crystalline form of a hydrochloride solvate of 3-(1-{3-[5-(1-methyl-piperidin-4-ylmethoxy)-pyrimidin-2-yl]-benzyl}-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzonitrile, excluding 3-(1-{3-[5-(1-methyl-piperidin-4-ylmethoxy)-pyrimidin-2-yl]-benzyl}-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzonitrile hydrochloride monohydrate in the form of a polymorph characterized by the following XRD data:°2θ (Cu—Kα1Peak No.d/Åradiation)(h, k, l)18.7110.1(1, 0, 0)28.2210.8(−1, 1, 1)37.5911.6(1, 2, 0)46.7813.0(0, 3, 1)56.5813.5(−1, 3, 1)65.7315.4(−1, 4, 1)74.9817.8(−1, 1, 2)84.8418.3(−2, 1, 1)94.6819.0(−2, 2, 1)104.4320.0(−2, 3, 1)114.3520.4(2, 0, 0)123.7323.9(−2, 4, 2)133.6424.5(0, 5, 2)143.3926.3(0, 6, 2)153.1328.5(−3, 2, 2) or (b) the hydrochloride anhydrate of the compound 3-(1-{3-[5-(1-methyl-piperidin-4-ylmethoxy)-pyrimidin-2-yl]-benzyl}-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzonitrile. |
