发明名称 |
Malate salt of N-(4-phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms therof for the treatment of cancer |
摘要 |
Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide. |
申请公布号 |
US2015057310(A1) |
申请公布日期 |
2015.02.26 |
申请号 |
US201414340871 |
申请日期 |
2014.07.25 |
申请人 |
Exelixis, Inc. |
发明人 |
Brown Adrian St. Clair;Lamb Peter;Gallagher William P. |
分类号 |
C07D215/22 |
主分类号 |
C07D215/22 |
代理机构 |
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代理人 |
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主权项 |
1. N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (L) malate salt, wherein said salt is in crystalline Form N-1 and said Form N-1 is characterized by at least one of the following:
(i) a solid state 13C NMR spectrum with four or more peaks selected from 18.1, 42.9, 44.5, 70.4, 123.2, 156.2, 170.8, 175.7, and 182.1, ±0.2 ppm; (ii) a powder x-ray diffraction pattern (CuKα λ=1.5418 Å) comprising four or more 2θ values selected from: 12.8±0.2 °2θ, 13.5±0.2 °2θ, 16.9±0.2 °2θ, 19.4±0.2 °2θ, 21.5±0.2 °2θ, 22.8±0.2 °2θ, 25.1±0.2 °2θ, 27.6±0.2 °2θ, wherein measurement of the crystalline form is at room temperature; and/or (iii) an x-ray powder diffraction (XRPD) pattern substantially in accordance with the pattern shown in FIG. 1. |
地址 |
South San Francisco CA US |