25-10-2012 дата публикации
Номер: US20120270872A1
This invention relates to three crystalline forms of N—[3-fluoro-4-((6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl|oxy)phenyl]—N′—(4-fluorophenyl)cyclopropane-1,1-dicarboxamide. Compound (I), designated as Form A, Form B, and Form C. The invention provides methods for treatment of cancer by exploiting the modulation of protein kinase activity. The invention also provides pharmaceutical compositions containing a crystalline form of Compound (I) and a pharmaceutically acceptable excipient. 1. A crystalline form of N—[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]—N′—(4-fluorophenyl)cyclopropane-1 ,1-dicarboxamide characterized by having at least one of:{'sup': '13', 'a solid state C NMR spectrum with peaks at 161.2, 158.6, 153.3, 146.5, 136.0, 132.6, 128.6, 127.4, and 124.9 ppm±0.2 ppm;'}{'sup': '19', 'sub': '3', 'a solid state F NMR spectrum with peaks at −116.8 and −128.6 ppm±0.2 ppm relative to CFCl; and'}an X-ray powder diffraction pattern with peaks at 7.2, 7.7, 12.5, 15.5, 16.5, 17.1, and 19.1 °2θ±0.7°2θ.2. A crystalline form of N—[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]—N′—(4-fluorophenyl)cyclopropane-1 claim 1 ,1-dicarboxamide according to characterized by at least two of:an X-ray powder diffraction pattern with peaks at 7.2, 7.7, 12.5, 15.5, 16.5, 17.1, and 19.1 °2θ±0.2°2θ:{'sup': '13', 'a solid state C NMR spectrum with peaks at 161.2, 158.6, 153.3, 146.5, 136.0, 132.6, 128.6, 127.4, and 124.9 ppm±0.2 ppm; and'}{'sup': '19', 'sub': '3', 'a solid state F NMR spectrum with peaks at −116.8 and −128.6 ppm±0.2 ppm relative to CFCl.'}3. A crystalline form of N—[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]—N′—(4-fluorophenyl)cyclopropane-1 claim 1 ,1-dicarboxamide characterized by having at least one of:{'sup': '13', 'a solid state C NMR spectrum with peaks at 162.7, 160.5, 147.4, 137.9, 133.5, 131.4, 126.1, and 122.7 ppm±0.2 ppm;'}{' ...
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