CN105622577A - Novel crystallographic form of ceritinib and preparation method of novel crystallographic form - Google Patents
Novel crystallographic form of ceritinib and preparation method of novel crystallographic form Download PDFInfo
- Publication number
- CN105622577A CN105622577A CN201410714723.8A CN201410714723A CN105622577A CN 105622577 A CN105622577 A CN 105622577A CN 201410714723 A CN201410714723 A CN 201410714723A CN 105622577 A CN105622577 A CN 105622577A
- Authority
- CN
- China
- Prior art keywords
- carcinoma
- auspicious
- color
- buddhist nun
- crystal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- VERWOWGGCGHDQE-UHFFFAOYSA-N ceritinib Chemical compound CC=1C=C(NC=2N=C(NC=3C(=CC=CC=3)S(=O)(=O)C(C)C)C(Cl)=CN=2)C(OC(C)C)=CC=1C1CCNCC1 VERWOWGGCGHDQE-UHFFFAOYSA-N 0.000 title abstract description 6
- 229960001602 ceritinib Drugs 0.000 title abstract description 5
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 9
- 102100033793 ALK tyrosine kinase receptor Human genes 0.000 claims abstract description 8
- 201000010099 disease Diseases 0.000 claims abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 5
- 101710168331 ALK tyrosine kinase receptor Proteins 0.000 claims abstract description 4
- 239000013078 crystal Substances 0.000 claims description 60
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- 206010009944 Colon cancer Diseases 0.000 claims description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 238000001291 vacuum drying Methods 0.000 claims description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 4
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 4
- 208000012609 Cowden disease Diseases 0.000 claims description 4
- 101000779641 Homo sapiens ALK tyrosine kinase receptor Proteins 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- 208000008770 Multiple Hamartoma Syndrome Diseases 0.000 claims description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 4
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 206010017758 gastric cancer Diseases 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 201000011549 stomach cancer Diseases 0.000 claims description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- 238000010521 absorption reaction Methods 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical class CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 claims description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 2
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 201000009030 Carcinoma Diseases 0.000 claims description 2
- 208000017897 Carcinoma of esophagus Diseases 0.000 claims description 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
- 206010048832 Colon adenoma Diseases 0.000 claims description 2
- 201000002847 Cowden syndrome Diseases 0.000 claims description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 2
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 2
- 208000032612 Glial tumor Diseases 0.000 claims description 2
- 206010018338 Glioma Diseases 0.000 claims description 2
- 201000003803 Inflammatory myofibroblastic tumor Diseases 0.000 claims description 2
- 206010067917 Inflammatory myofibroblastic tumour Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 2
- 208000028018 Lymphocytic leukaemia Diseases 0.000 claims description 2
- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 2
- 206010029260 Neuroblastoma Diseases 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 claims description 2
- 206010034811 Pharyngeal cancer Diseases 0.000 claims description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 206010054184 Small intestine carcinoma Diseases 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 2
- 208000033781 Thyroid carcinoma Diseases 0.000 claims description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
- 201000005179 adrenal carcinoma Diseases 0.000 claims description 2
- 201000005188 adrenal gland cancer Diseases 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 2
- 201000008275 breast carcinoma Diseases 0.000 claims description 2
- 208000003362 bronchogenic carcinoma Diseases 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 238000005119 centrifugation Methods 0.000 claims description 2
- 201000010881 cervical cancer Diseases 0.000 claims description 2
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 2
- 210000001072 colon Anatomy 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- KQTXIZHBFFWWFW-UHFFFAOYSA-L disilver;carbonate Chemical compound [Ag]OC(=O)O[Ag] KQTXIZHBFFWWFW-UHFFFAOYSA-L 0.000 claims description 2
- 201000003914 endometrial carcinoma Diseases 0.000 claims description 2
- 201000005619 esophageal carcinoma Diseases 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 150000002460 imidazoles Chemical class 0.000 claims description 2
- 201000007450 intrahepatic cholangiocarcinoma Diseases 0.000 claims description 2
- 201000005264 laryngeal carcinoma Diseases 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 2
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 2
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 claims description 2
- 208000003747 lymphoid leukemia Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 2
- 210000000214 mouth Anatomy 0.000 claims description 2
- 208000025113 myeloid leukemia Diseases 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 201000005443 oral cavity cancer Diseases 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- 238000001556 precipitation Methods 0.000 claims description 2
- 201000001514 prostate carcinoma Diseases 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- 206010038038 rectal cancer Diseases 0.000 claims description 2
- 201000003780 rectum adenoma Diseases 0.000 claims description 2
- 201000001275 rectum cancer Diseases 0.000 claims description 2
- 201000010174 renal carcinoma Diseases 0.000 claims description 2
- 201000007444 renal pelvis carcinoma Diseases 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 239000001488 sodium phosphate Substances 0.000 claims description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 2
- 235000011008 sodium phosphates Nutrition 0.000 claims description 2
- 201000010700 sporadic breast cancer Diseases 0.000 claims description 2
- 239000001117 sulphuric acid Substances 0.000 claims description 2
- 235000011149 sulphuric acid Nutrition 0.000 claims description 2
- 201000002510 thyroid cancer Diseases 0.000 claims description 2
- 208000013077 thyroid gland carcinoma Diseases 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 claims description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 206010046885 vaginal cancer Diseases 0.000 claims description 2
- 208000013139 vaginal neoplasm Diseases 0.000 claims description 2
- 230000007704 transition Effects 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 6
- 230000001404 mediated effect Effects 0.000 abstract 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- 239000008213 purified water Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000000113 differential scanning calorimetry Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000002441 X-ray diffraction Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000013019 agitation Methods 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000001376 precipitating effect Effects 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000002177 L01XE27 - Ibrutinib Substances 0.000 description 2
- 150000003851 azoles Chemical class 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229960001507 ibrutinib Drugs 0.000 description 2
- XYFPWWZEPKGCCK-GOSISDBHSA-N ibrutinib Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C=C)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XYFPWWZEPKGCCK-GOSISDBHSA-N 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 238000002411 thermogravimetry Methods 0.000 description 2
- 229940122531 Anaplastic lymphoma kinase inhibitor Drugs 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 239000002146 L01XE16 - Crizotinib Substances 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960005061 crizotinib Drugs 0.000 description 1
- KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940052129 zykadia Drugs 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a novel crystallographic form of ceritinib. An X-ray powder diffraction pattern of the novel crystallographic form of ceritinib is as shown in Figure 1. The invention further relates to a method for preparing the crystallographic form, and application of the crystallographic form to preparation of a medicament for treating anaplastic lymphoma kinase mediated diseases.
Description
Technical field
The present invention relates to organic chemistry filed and biomedicine field, relate to color auspicious for a kind of novel crystal forms C of Buddhist nun, Preparation Method And The Use.
Background technology
Color is auspicious for the Buddhist nun's chemistry chloro-N-of 5-(2-isopropoxy-5-methyl-4-(piperidin-4-yl phenyl)-N-2-(isopropelsulfonyl) phenyl)-2,4-diamidogen by name, and structural formula is such as shown in following formula I:
Color is auspicious for Buddhist nun (Ceritinib, original name LDK378) it is a kind of gradually changeable lymphoma enzyme (ALK) the TYR inhibitors of kinases researched and developed by Novartis (Novartis), this medicine is used for the treatment of existing progression of disease or not tolerant transitivity NSCLC patient after gram azoles is for Buddhist nun (Crizotinib) treatment in April, 2014 by FDA approval, and commodity are called Zykadia. Color is auspicious is for second ALK inhibitor of FDA approval after Buddhist nun continue gram azoles for Buddhist nun, is also second medicine giving special approval to passage listing through quadruple after Ibrutinib (Ibrutinib).
It is auspicious for Buddhist nun and preparation method thereof that patent WO2008/073687A1 discloses and protect color; in addition; WO2009120798, WO2008073687, WO2004080980; WO20140066406; WO2011140338, WO209143389, WO2008073687; the patents such as WO2009126515 also disclose the auspicious preparation method for Buddhist nun of color respectively, but its crystal formation is mentioned.
Patent application CN103282359A discloses auspicious two kinds of crystal form A and the B for Buddhist nun of color.
This patent is pointed out, the auspicious XRPD for the crystal form A of Buddhist nun of color is presented in lower group of angle of diffraction place the diffraction maximum of maximum:: 7.2 ��, 8.1 ��, 10.8 ��, 12.0 ��, 12.4 ��, 13.4 ��, 14.4 ��, 14.8 ��, 15.7 ��, 16.9 ��, 17.7 ��, 18.5 ��, 19.0 ��, 19.5 ��, 20.0 ��, 20.3 ��, 21.1 ��, 21.6 ��, 22.4 ��, 22.6 ��, 23.0 ��, 24.1 ��, 24.5 ��, 25.5 ��, 26.0 ��, 26.2 ��, 27.0 ��, 27.3 ��, 28.3 ��, 29.0 ��, 29.1 ��, 30.6 ��, 31.3 ��, 32.8 ��, 33.5 ��, 34.2 �� and 36.4 �� (2 �� degree). , being measured by differential scanning calorimetry, its fusing point is 174 DEG C. , being measured by thermogravimetric analysis, higher than 250 DEG C and at 200 DEG C, loss on drying is 0.1% to its decomposition point.
This patent is pointed out, the auspicious XRPD for the crystal form B of Buddhist nun of color is presented in lower group of angle of diffraction place the diffraction maximum of maximum:: 5.1 ��, 5.5 ��, 5.6 ��, 9.5 ��, 9.6 ��, 10.1 ��, 11.0 ��, 11.8 ��, 12.1 ��, 12.6 ��, 13.7 ��, 14.5 ��, 14.9 ��, 15.2 ��, 16.1 ��, 16.6 ��, 16.7 ��, 17.0 ��, 17.1 ��, 17.5 ��, 17.7 ��, 18.0 ��, 18.8 ��, 19.0 ��, 19.3 ��, 19.5 ��, 20.5 ��, 20.9 ��, 21.5 ��, 21.9 ��, 22.1 ��, 22.4 ��, 22.8 ��, 23.2 ��, 23.7 ��, 23.9 ��, 24.3 ��, 24.5 ��, 24.8 ��, 25.1 ��, 25.4 ��, 25.9 ��, 26.4 ��, 26.8 ��, 27.8 ��, 28.1 ��, 28.6 ��, 29.1 ��, 29.6 ��, 29.8 ��, 30.6 ��, 31.6 ��, 32.7 ��, 33.5 ��, 34.2 ��, 35.4 ��, 35.6 �� and 36.8 �� (2 �� degree). , being measured by differential scanning calorimetry, its fusing point is 162 DEG C. , being measured by thermogravimetric analysis, higher than 250 DEG C and at 200 DEG C, loss on drying is 0.05% to its decomposition point.
The present inventor is in the research auspicious process for Buddhist nun's crystal formation of color, finding and prepare the auspicious another kind of novel crystal forms for Buddhist nun of color, it has and is significantly different from existing X-ray powder diffraction feature, and preparation method is simple, chemical stability is excellent, is suitable for use in several formulations.
Summary of the invention
It is an object of the invention to provide the auspicious crystal formation for Buddhist nun of a kind of new color, temporary called after crystal C.
It is a further object of the present invention to provide the method preparing the auspicious above-mentioned novel crystal forms C for Buddhist nun of color.
The purpose of the present invention can be realized by following approach:
The auspicious feature for Buddhist nun novel crystal forms C of color of the present invention:
Color provided by the invention is auspicious for Buddhist nun novel crystal forms C, and to spend the 2 �� X-ray Powder Diffraction pattern represented at 5.6 ��, 9.5 ��, 12.6 ��, 15.2 ��, 16.2 ��, 16.6 ��, 18.8 ��, there is characteristic diffraction peak at 25.9 �� of places.
Above-mentioned color of the present invention is auspicious for Buddhist nun novel crystal forms C, still further comprises 2 �� values at 8.3 ��, 11.0 ��, 11.9 ��, 12.2 ��, 14.5 ��, 17.0 ��, 17.6 ��, 19.0 ��, 19.5 ��, 20.6 ��, 21.0 ��, 21.7 ��, 21.9 ��, 22.2 ��, 22.4 ��, 22.9 ��, 23.9 ��, 24.3 ��, 24.9 ��, 25.1 ��, 28.1 ��, 28.7 ��, 29.8 ��, 30.7 ��, the position of 31.6 �� is to there being characteristic diffraction peak.
Color provided by the invention is auspicious for Buddhist nun novel crystal forms C, and its x-ray diffraction pattern is as shown in Figure 1.
Color provided by the invention is auspicious relatively sees Fig. 2 for the x-ray diffraction pattern of crystal form A, crystal form B disclosed in Buddhist nun novel crystal forms C and patent application CN103282359A.
It is understandable that, owing to being subject to the impact of many factors (during such as the granularity of test sample, test the processing method of sample, instrument, test parameter, test operation etc.), the X-ray powder diffraction measured by same crystal formation go out peak position or peak intensity has certain difference. In X-ray powder diffraction, the experimental error of diffraction maximum 2 �� value can be �� 0.2 ��.
The differential scanning calorimetry (DSC) of the auspicious novel crystal forms C for Buddhist nun of color of the present invention, it absorbs and changes at 164 �� 2 DEG C.
Differential scanning calorimetry (DSC) figure of the auspicious novel crystal forms C for Buddhist nun of color of the present invention is as shown in Figure 3.
The auspicious infrared absorption pattern recorded for the novel crystal forms C KBr tabletting of Buddhist nun of color of the present invention, is characterized by 3418.6cm-1, 3311.0cm-1, 1597.5cm-1, 1568.7cm-1, 1508.3cm-1, there is absworption peak at place.
The auspicious infrared absorption pattern recorded for the novel crystal forms C KBr tabletting of Buddhist nun of the color of the present invention is as shown in Figure 4.
The auspicious novel crystal forms C for Buddhist nun of color of the present invention, the content (mass content) of its crystal C is generally higher than 70%, it is preferable that more than 80%, optimum more than 90%.
The preparation method that present invention also offers the auspicious novel crystal forms C for Buddhist nun of a kind of color, the method includes dissociating crystallize out by the method for alkali adjustment pH value for Buddhist nun by auspicious for color from souring soln, is separated by crystal, dry, it is thus achieved that novel crystal forms C.
In one specific embodiment, the auspicious preparation method for Buddhist nun novel crystal forms C of color comprises the following steps:
1) dissipating auspicious for color with moisture for Buddhist nun, add suitable acid or acid solution, make system dissolve, obtain the auspicious solution for Buddhist nun's salt of color, solution temperature is 0��60 DEG C, it is preferable that 5��20 DEG C;
2) auspicious for Buddhist nun's saline solution adds suitable alkali or aqueous slkali to above-mentioned color, regulate pH value, make color auspicious for Buddhist nun's crystallize out, and continue stirring 24��168h, recrystallization temperature is 0��60 DEG C, it is preferable that 5��20 DEG C, regulates pH to pH6��14, it is preferable that pH9��12;
3) crystal of precipitation is filtered or centrifugation;
4) carrying out vacuum drying by separating the crystal obtained, baking temperature is 30��150 DEG C, it is preferable that 80��120 DEG C.
In the method for the embodiment above, step 1) described in acid or acid solution include but not limited in hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, nitric acid, formic acid, acetic acid, p-methyl benzenesulfonic acid, methanesulfonic acid, benzenesulfonic acid one or more. Step 2) described in alkali or aqueous slkali be potassium hydroxide, sodium hydroxide, Lithium hydrate, potassium carbonate, sodium carbonate, cesium carbonate, lithium carbonate, Disilver carbonate, sodium bicarbonate, potassium phosphate, sodium phosphate, potassium acetate, sodium acetate, trimethylamine, triethylamine, tri-n-butylamine, 4-dimethylamino pyridine, N, N-dimethylaniline, 1,8-diazabicylo [5.4.0] 11 carbon-7-alkene, N-methylmorpholine, N, N-diisopropylethylamine, pyridine, 2,6-lutidines, imidazoles, N, N, N ', N ' one or more in-tetramethylethylenediamine.
It is a further object to provide the described color auspicious crystal C for Buddhist nun purposes in the medicament of the disease of preparation treatment anaplastic lymphoma kinase ALK Alk receptor tyrosine kinase mediation.
The disease of preferably described anaplastic lymphoma kinase ALK Alk receptor tyrosine kinase mediation is cancer.
Preferred described cancer is primary cutaneous type, non Hodgkin lymphom (non-Hodgkin'slymphoma), Inflammatory myofibroblastic tumor, neuroblastoma, sarcoma, pulmonary carcinoma, bronchogenic carcinoma, carcinoma of prostate, breast carcinoma (comprises sporadic breast carcinoma and cowden's disease (Cowdendisease) patient), cancer of pancreas, human primary gastrointestinal cancers, colon cancer, rectal cancer, colon carcinoma (coloncarcinoma), Colon and rectum adenoma, thyroid carcinoma, hepatocarcinoma, intrahepatic cholangiocarcinoma, hepatocarcinoma, adrenal carcinoma, gastric cancer, stomach cancer, glioma, gliablastoma, carcinoma of endometrium, melanoma, renal carcinoma, carcinoma of renal pelvis, bladder cancer, carcinoma of uterine body, cervical cancer, cancer of vagina, ovarian cancer, multiple myeloma, esophageal carcinoma, leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, Lymphocytic leukemia, myeloid leukemia, the brain cancer, brain cancer tumor, oral cavity and pharyngeal cancer, laryngeal carcinoma, carcinoma of small intestine and melanoma.
The auspicious stability study for Buddhist nun novel crystal forms C of color of the present invention:
Uniformly share auspicious for color to uncovered culture dish for Buddhist nun's crystal C, be positioned under the influence factors such as illumination, high temperature, high humidity, separately sampled detection, and with 0 day result compare. Result is in Table 1.
Table 1 color is auspicious for Buddhist nun's crystal C study on the stability
By above-mentioned result of the test it can be seen that the color that obtains of the present invention auspicious for Buddhist nun novel crystal forms C under the conditions such as illumination, high temperature, high humidity, purity is without large change, stable crystal form. Color provided by the invention is auspicious stable for Buddhist nun's crystal C physicochemical properties, is suitable to long storage periods and is applied to preparation.
Accompanying drawing explanation
Fig. 1 is the auspicious x-ray diffraction pattern for Buddhist nun's crystal C of color of the present invention.
Fig. 2 is that the auspicious x-ray diffraction pattern for crystal form A disclosed in Buddhist nun's crystal C and patent application CN103282359A, crystal form B of color of the present invention compares.
Fig. 3 is the auspicious crystal DSC spectrogram for Buddhist nun's crystal C of color of the present invention.
Fig. 4 is the auspicious crystal IR spectrogram for Buddhist nun's crystal C of color of the present invention.
Detailed description of the invention
Below in conjunction with embodiment, the invention will be further described, it is possible to makes professional and technical personnel in the field be more completely understood by the present invention, but the scope not limited the present invention in any way.
Embodiment 1
(it is equipped with mechanical agitation to the four-hole boiling flask of 2L; thermometer; nitrogen protection; constant pressure funnel) in add color auspicious for Buddhist nun's free alkali (100.0g); it is subsequently added purified water (1L) stirring, controls system temperature 20 DEG C, add hydrochloric acid (6N; 0.22L), nitrogen protection borehole cooling to 15 DEG C. Being added drop-wise in reaction system by sodium hydroxide solution (3N, 0.53L), time for adding controls 120 minutes, starts slowly to become cloudy after dropping a period of time, comparatively fast precipitates out solid subsequently, continues stirring 168 hours after precipitating out solid. Filtering, filter cake purified water (500ml �� 3) is washed, and after vacuum takes out pressure (carrying out under nitrogen protection), is placed in vacuum drying oven by product at 80 DEG C and dries 96h, obtain color auspicious for Buddhist nun crystal C (64g, yield 72%).
Embodiment 2
(it is equipped with mechanical agitation to the four-hole boiling flask of 5L; thermometer; nitrogen protection; constant pressure funnel) in add color auspicious for Buddhist nun (200.0g); it is subsequently added purified water (2L) stirring, controls system temperature 10 DEG C, add hydrochloric acid (3N; 0.8L), nitrogen protection borehole cooling to 5 DEG C. Being added drop-wise in reaction system by potassium hydroxide solution (3N, 0.8L), time for adding controls at 60 minutes, starts slowly to become cloudy after dropping a period of time, comparatively fast precipitates out solid subsequently, at room temperature continues stirring 24 hours after precipitating out solid. Filtering, filter cake purified water (1L �� 3) is washed, and after vacuum takes out pressure (carrying out under nitrogen protection), is placed in vacuum drying oven by product at 100 DEG C and dries 2h, obtain color auspicious for Buddhist nun crystal C (176g, yield 88%).
Embodiment 3
(it is equipped with mechanical agitation to the four-hole boiling flask of 5L; thermometer; nitrogen protection; constant pressure funnel) in add color auspicious for Buddhist nun (200.0g); it is subsequently added purified water (2L) stirring, controls system temperature 5 DEG C, add sulfuric acid solution (6N; 0.22L), under nitrogen protection temperature control to 20 DEG C. Being added drop-wise in reaction system by ammonia (7N, 0.5L), time for adding controls at 180 minutes, starts slowly to become cloudy after dropping a period of time, comparatively fast precipitates out solid subsequently, continues stirring 72 hours after precipitating out solid. Filtering, filter cake purified water (1L �� 3) is washed, and after vacuum takes out pressure (carrying out under nitrogen protection), is placed in vacuum drying oven by product at 120 DEG C and dries 2h, obtain color auspicious for Buddhist nun crystal C (170g, yield 85%).
Claims (10)
1. the auspicious crystal C for Buddhist nun of color, it is characterised in that: to spend the 2 �� X-ray Powder Diffraction pattern represented at 5.6 ��, 9.5 ��, 12.6 ��, 15.2 ��, 16.2 ��, 16.6 ��, 18.8 ��, the position of 25.9 �� is to there being characteristic diffraction peak.
2. crystal C as claimed in claim 1, still further comprises 2 �� values at 8.3 ��, 11.0 ��, 11.9 ��, 12.2 ��, 14.5 ��, 17.0 ��, 17.6 ��, 19.0 ��, 19.5 ��, 20.6 ��, 21.0 ��, 21.7 ��, 21.9 ��, 22.2 ��, 22.4 ��, 22.9 ��, 23.9 ��, 24.3 ��, 24.9 ��, 25.1 ��, 28.1 ��, 28.7 ��, 29.8 ��, 30.7 ��, the position of 31.6 �� is to there being characteristic diffraction peak.
3. crystal C as claimed in claim 1, it is characterised in that: the X-ray powder diffraction figure of described crystal is as shown in Figure 1.
4. the auspicious crystal C for Buddhist nun of color as claimed in claim 1, its DSC endothermic transition is at 164 �� 2 DEG C.
5. the auspicious crystal C for Buddhist nun of color as claimed in claim 1, its infrared absorption pattern has absworption peak at 3418.6cm-1,3311.0cm-1,1597.5cm-1,1568.7cm-1,1508.3cm-1 place.
6. crystal C as claimed in claim 1, its content is more than 70%, it is preferable that more than 80%, optimum more than 90%.
7. the preparation method of the auspicious crystal C for Buddhist nun of color described in a claim 1, it is characterised in that:
1) dissipating auspicious for color with moisture for Buddhist nun, add suitable acid or acid solution, make system dissolve, obtain the auspicious solution for Buddhist nun's salt of color, solution temperature is 0��60 DEG C, it is preferable that 5��20 DEG C;
2) auspicious for Buddhist nun's saline solution adds suitable alkali or aqueous slkali to above-mentioned color, regulate pH value, make color auspicious for Buddhist nun's crystallize out, and continue stirring 24��168h, recrystallization temperature is 0��60 DEG C, it is preferable that 5��20 DEG C, regulates pH to pH6��14, it is preferable that pH9��12;
3) crystal of precipitation is filtered or centrifugation;
4) carrying out vacuum drying by separating the crystal obtained, baking temperature is 30��150 DEG C, it is preferable that 80��120 DEG C.
8. preparation method as claimed in claim 7, it is characterised in that described acid or acid solution include but not limited to one or more in hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, nitric acid, formic acid, acetic acid, p-methyl benzenesulfonic acid, methanesulfonic acid, benzenesulfonic acid; Described alkali or aqueous slkali are potassium hydroxide, sodium hydroxide, Lithium hydrate, potassium carbonate, sodium carbonate, cesium carbonate, lithium carbonate, Disilver carbonate, sodium bicarbonate, potassium phosphate, sodium phosphate, potassium acetate, sodium acetate, trimethylamine, triethylamine, tri-n-butylamine, 4-dimethylamino pyridine, N, N-dimethylaniline, 1,8-diazabicylo [5.4.0] 11 carbon-7-alkene, N-methylmorpholine, N, N-diisopropylethylamine, pyridine, 2,6-lutidines, imidazoles, N, N, N ', N ' one or more in-tetramethylethylenediamine.
9. the color as claimed in claim 1 auspicious crystal C for Buddhist nun purposes in the medicament of the disease of preparation treatment anaplastic lymphoma kinase ALK Alk receptor tyrosine kinase mediation.
10. purposes as claimed in claim 9, wherein said disease is the cancer selected from lower group: primary cutaneous type, non Hodgkin lymphom (non-Hodgkin'slymphoma), Inflammatory myofibroblastic tumor, neuroblastoma, sarcoma, pulmonary carcinoma, bronchogenic carcinoma, carcinoma of prostate, breast carcinoma (comprises sporadic breast carcinoma and cowden's disease (Cowdendisease) patient), cancer of pancreas, human primary gastrointestinal cancers, colon cancer, rectal cancer, colon carcinoma (coloncarcinoma), Colon and rectum adenoma, thyroid carcinoma, hepatocarcinoma, intrahepatic cholangiocarcinoma, hepatocarcinoma, adrenal carcinoma, gastric cancer, stomach cancer, glioma, gliablastoma, carcinoma of endometrium, melanoma, renal carcinoma, carcinoma of renal pelvis, bladder cancer, carcinoma of uterine body, cervical cancer, cancer of vagina, ovarian cancer, multiple myeloma, esophageal carcinoma, leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, Lymphocytic leukemia, myeloid leukemia, the brain cancer, brain cancer tumor, oral cavity and pharyngeal cancer, laryngeal carcinoma, carcinoma of small intestine and melanoma.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410714723.8A CN105622577A (en) | 2014-11-29 | 2014-11-29 | Novel crystallographic form of ceritinib and preparation method of novel crystallographic form |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410714723.8A CN105622577A (en) | 2014-11-29 | 2014-11-29 | Novel crystallographic form of ceritinib and preparation method of novel crystallographic form |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105622577A true CN105622577A (en) | 2016-06-01 |
Family
ID=56037960
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410714723.8A Pending CN105622577A (en) | 2014-11-29 | 2014-11-29 | Novel crystallographic form of ceritinib and preparation method of novel crystallographic form |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105622577A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2651918B1 (en) | 2010-12-17 | 2017-07-12 | Novartis AG | Crystalline forms of 5-chloro-n2-(2-isopropoxy-5-methyl-4-piperidin-4-yl-phenyl)-n4[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine |
| CN108314676A (en) * | 2017-01-18 | 2018-07-24 | 上海医药工业研究院 | The aminopyridine analog derivative and its antitumor application thereof of the segment containing hydroxamic acid |
| WO2021143819A1 (en) * | 2020-01-17 | 2021-07-22 | 山东轩竹医药科技有限公司 | Crystal form of polycyclic anaplastic lymphoma kinase inhibitor |
| CN114901289A (en) * | 2019-10-28 | 2022-08-12 | 奥斯陆大学 | ALK inhibitors for the treatment of ALK negative cancers and plasma cell mediated diseases |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103282359A (en) * | 2010-12-17 | 2013-09-04 | 诺华股份有限公司 | Crystalline forms of 5-chloro-N2-(2-isopropoxy-5-methyl-4-piperidin-4-yl-phenyl)-N4[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine |
-
2014
- 2014-11-29 CN CN201410714723.8A patent/CN105622577A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103282359A (en) * | 2010-12-17 | 2013-09-04 | 诺华股份有限公司 | Crystalline forms of 5-chloro-N2-(2-isopropoxy-5-methyl-4-piperidin-4-yl-phenyl)-N4[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2651918B1 (en) | 2010-12-17 | 2017-07-12 | Novartis AG | Crystalline forms of 5-chloro-n2-(2-isopropoxy-5-methyl-4-piperidin-4-yl-phenyl)-n4[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine |
| EP3121171B1 (en) | 2010-12-17 | 2018-08-15 | Novartis Ag | Crystalline forms of 5-chloro-n2-(2-isopropoxy-5-methyl-4-piperidin-4-yl-phenyl)-n4[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine |
| CN108314676A (en) * | 2017-01-18 | 2018-07-24 | 上海医药工业研究院 | The aminopyridine analog derivative and its antitumor application thereof of the segment containing hydroxamic acid |
| CN108314676B (en) * | 2017-01-18 | 2020-07-14 | 上海医药工业研究院 | Amino pyridine derivative containing hydroxamic acid fragment and anti-tumor application thereof |
| CN114901289A (en) * | 2019-10-28 | 2022-08-12 | 奥斯陆大学 | ALK inhibitors for the treatment of ALK negative cancers and plasma cell mediated diseases |
| WO2021143819A1 (en) * | 2020-01-17 | 2021-07-22 | 山东轩竹医药科技有限公司 | Crystal form of polycyclic anaplastic lymphoma kinase inhibitor |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2013545812A (en) | Of 5-chloro-N2- (2-isopropoxy-5-methyl-4-piperidin-4-yl-phenyl) -N4 [2- (propane-2-sulfonyl) -phenyl] -pyrimidine-2,4-diamine Crystal form | |
| AU2017371134B2 (en) | Pharmaceutical composition for preventing or treating liver cancer, comprising tetraarsenic hexoxide crystalline polymorph | |
| CN118459459A (en) | Heterocyclic compound and its preparation method and use | |
| KR101829595B1 (en) | Novel polymorphic forms of 3-(1-{3-[5-(1-methyl-piperidin-4ylmethoxy)-pyrimidin-2-yl]-benzyl}-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzonitrile hydrochloride salt and processes of manufacturing thereof | |
| IL235297A (en) | DNA-pk suppressors, preparations containing them and their uses | |
| CN105622577A (en) | Novel crystallographic form of ceritinib and preparation method of novel crystallographic form | |
| CN103974949A (en) | Crystalline form i of tyrosine kinase inhibitor dimaleate and preparation methods thereof | |
| TW201427956A (en) | Preparation of MEK inhibitors and formulations comprising MEK inhibitors | |
| JP6779972B2 (en) | N-[(3-amino-3-oxetanyl) methyl] -2- (2,3-dihydro-1,1-dioxide-1,4-benzo) for the treatment of respiratory syncytial virus (RSV) infections Crystal form of thiazepine-4 (5H) -yl) -6-methyl-4-quinazolineamine | |
| TW201925207A (en) | Salts of 4-amino-N-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-D]pyrimidine-7-carboxamide, and crystalline forms thereof | |
| CN112010839A (en) | Crystalline forms of a targeted silk/threonine kinase inhibitor | |
| US10323035B2 (en) | Co-crystal of a CDK inhibitor and an MEK inhibitor and process of preparation thereof | |
| CN102070618A (en) | Compound and crystals thereof | |
| CN105294649B (en) | A kind of Ceritinib compound and its pharmaceutical composition | |
| CN103664890A (en) | Crystal of quinoline derivative and preparation method of crystal | |
| CN104119321B (en) | The 2-maleate and its polymorph of indolinone derivative | |
| CN104557869B (en) | A kind of crystal formation of pyridinylamine compound fumarate | |
| CN106117199A (en) | The dihydroxy ethyl sulfonate of a kind of cell cycle protein dependent kinase inhibitor, its crystal form and preparation method thereof | |
| CN110790748B (en) | Crystal form of p-toluenesulfonate of cyclin dependent kinase inhibitor and preparation method and application thereof | |
| WO2017152858A1 (en) | Crystal form of ceritinib and preparation method thereof | |
| JP7710449B2 (en) | Heterocyclic compounds and their preparation and use | |
| CN104470929B (en) | The crystal form of Conmana and its application | |
| CN107629048A (en) | A kind of crystal form of malate of tyrosine kinase inhibitor and preparation method thereof | |
| CN108752318A (en) | A kind of crystal form of polyfluoro substitution virtue connection heterocycle compound, preparation method and application | |
| CN104961688A (en) | Phosphate of epidermal growth factor receptor kinase inhibitor and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20201229 Address after: 570311 No. 2 Yaogu No. 3 Road, Xiuying District, Haikou City, Hainan Province Applicant after: Hainan Simcere Pharmaceutical Co.,Ltd. Applicant after: JIANGSU SIMCERE PHARMACEUTICAL Co.,Ltd. Address before: 210042 699 Xuanwu Road, Xuanwu District, Nanjing, Jiangsu -18 Applicant before: JIANGSU SIMCERE PHARMACEUTICAL Co.,Ltd. |
|
| TA01 | Transfer of patent application right | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160601 |
|
| RJ01 | Rejection of invention patent application after publication |