JP6666849B2 - カボザンチニブ製剤の投与 - Google Patents
カボザンチニブ製剤の投与 Download PDFInfo
- Publication number
- JP6666849B2 JP6666849B2 JP2016558004A JP2016558004A JP6666849B2 JP 6666849 B2 JP6666849 B2 JP 6666849B2 JP 2016558004 A JP2016558004 A JP 2016558004A JP 2016558004 A JP2016558004 A JP 2016558004A JP 6666849 B2 JP6666849 B2 JP 6666849B2
- Authority
- JP
- Japan
- Prior art keywords
- cabozantinib
- auc
- mean
- measured
- metabolite
- 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.)
- Active
Links
- ONIQOQHATWINJY-UHFFFAOYSA-N cabozantinib Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1)=CC=C1NC(=O)C1(C(=O)NC=2C=CC(F)=CC=2)CC1 ONIQOQHATWINJY-UHFFFAOYSA-N 0.000 title claims description 259
- 239000002176 L01XE26 - Cabozantinib Substances 0.000 title claims description 240
- 229960001292 cabozantinib Drugs 0.000 title claims description 239
- 238000002360 preparation method Methods 0.000 title description 7
- 239000002207 metabolite Substances 0.000 claims description 87
- 210000002381 plasma Anatomy 0.000 claims description 72
- 239000008194 pharmaceutical composition Substances 0.000 claims description 47
- 206010028980 Neoplasm Diseases 0.000 claims description 36
- 201000011510 cancer Diseases 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 22
- 238000009472 formulation Methods 0.000 claims description 9
- 210000000481 breast Anatomy 0.000 claims description 7
- 210000004072 lung Anatomy 0.000 claims description 7
- 201000001342 Fallopian tube cancer Diseases 0.000 claims description 6
- 208000013452 Fallopian tube neoplasm Diseases 0.000 claims description 6
- 210000001072 colon Anatomy 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- 210000004369 blood Anatomy 0.000 claims description 5
- 239000008280 blood Substances 0.000 claims description 5
- 210000001685 thyroid gland Anatomy 0.000 claims description 5
- 210000000988 bone and bone Anatomy 0.000 claims description 4
- 230000002496 gastric effect Effects 0.000 claims description 4
- 210000003734 kidney Anatomy 0.000 claims description 4
- 210000004185 liver Anatomy 0.000 claims description 4
- 210000003491 skin Anatomy 0.000 claims description 4
- 230000002611 ovarian Effects 0.000 claims description 3
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical group OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 49
- 238000000034 method Methods 0.000 description 46
- 238000004128 high performance liquid chromatography Methods 0.000 description 44
- 238000011084 recovery Methods 0.000 description 37
- 239000000523 sample Substances 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 150000001875 compounds Chemical class 0.000 description 31
- 210000002700 urine Anatomy 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 201000010099 disease Diseases 0.000 description 25
- 208000035475 disorder Diseases 0.000 description 24
- 239000000047 product Substances 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 17
- 238000000605 extraction Methods 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 239000006228 supernatant Substances 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 208000009956 adenocarcinoma Diseases 0.000 description 11
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 206010025323 Lymphomas Diseases 0.000 description 9
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical group O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 9
- 230000002503 metabolic effect Effects 0.000 description 9
- 150000003839 salts Chemical class 0.000 description 9
- 239000002002 slurry Substances 0.000 description 9
- -1 4-{[6,7-bis (methyloxy) quinolin-4-yl] oxy} phenyl Chemical group 0.000 description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
- 108091000080 Phosphotransferase Proteins 0.000 description 8
- 102000001253 Protein Kinase Human genes 0.000 description 8
- 201000011066 hemangioma Diseases 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- 102000020233 phosphotransferase Human genes 0.000 description 8
- 108060006633 protein kinase Proteins 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 206010039491 Sarcoma Diseases 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 206010041823 squamous cell carcinoma Diseases 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- 206010009944 Colon cancer Diseases 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 6
- 229930182851 human metabolite Natural products 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- 238000007884 metabolite profiling Methods 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 6
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 6
- 230000011664 signaling Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 206010006187 Breast cancer Diseases 0.000 description 5
- 208000026310 Breast neoplasm Diseases 0.000 description 5
- 206010007275 Carcinoid tumour Diseases 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 206010024612 Lipoma Diseases 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 208000002458 carcinoid tumor Diseases 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 208000005017 glioblastoma Diseases 0.000 description 5
- 238000001819 mass spectrum Methods 0.000 description 5
- 201000001441 melanoma Diseases 0.000 description 5
- MGNPLIACIXIYJE-UHFFFAOYSA-N n-fluoroaniline Chemical compound FNC1=CC=CC=C1 MGNPLIACIXIYJE-UHFFFAOYSA-N 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
- 239000005695 Ammonium acetate Substances 0.000 description 4
- 206010005949 Bone cancer Diseases 0.000 description 4
- 208000018084 Bone neoplasm Diseases 0.000 description 4
- 201000008808 Fibrosarcoma Diseases 0.000 description 4
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 4
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 208000007766 Kaposi sarcoma Diseases 0.000 description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 4
- 208000000453 Skin Neoplasms Diseases 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 229940043376 ammonium acetate Drugs 0.000 description 4
- 235000019257 ammonium acetate Nutrition 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 150000001793 charged compounds Chemical class 0.000 description 4
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 206010016629 fibroma Diseases 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 201000005787 hematologic cancer Diseases 0.000 description 4
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 4
- 201000010260 leiomyoma Diseases 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 201000007270 liver cancer Diseases 0.000 description 4
- 208000014018 liver neoplasm Diseases 0.000 description 4
- 201000005202 lung cancer Diseases 0.000 description 4
- 208000020816 lung neoplasm Diseases 0.000 description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 4
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 201000002528 pancreatic cancer Diseases 0.000 description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 description 4
- 150000002989 phenols Chemical class 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 201000000849 skin cancer Diseases 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical group ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 4
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010003571 Astrocytoma Diseases 0.000 description 3
- 229940126062 Compound A Drugs 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 3
- 206010018338 Glioma Diseases 0.000 description 3
- 206010018404 Glucagonoma Diseases 0.000 description 3
- 208000002927 Hamartoma Diseases 0.000 description 3
- 208000001258 Hemangiosarcoma Diseases 0.000 description 3
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 3
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 3
- 208000018142 Leiomyosarcoma Diseases 0.000 description 3
- 208000009018 Medullary thyroid cancer Diseases 0.000 description 3
- 208000034578 Multiple myelomas Diseases 0.000 description 3
- 206010033128 Ovarian cancer Diseases 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- 206010038389 Renal cancer Diseases 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 206010043276 Teratoma Diseases 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 208000015419 gastrin-producing neuroendocrine tumor Diseases 0.000 description 3
- 201000000052 gastrinoma Diseases 0.000 description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
- 206010022498 insulinoma Diseases 0.000 description 3
- 201000010985 invasive ductal carcinoma Diseases 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 201000010982 kidney cancer Diseases 0.000 description 3
- 238000004811 liquid chromatography Methods 0.000 description 3
- 208000025113 myeloid leukemia Diseases 0.000 description 3
- 201000008968 osteosarcoma Diseases 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 208000021255 pancreatic insulinoma Diseases 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 210000002307 prostate Anatomy 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 2
- HXGYPQKHBCZWKO-UHFFFAOYSA-N 1-[[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]carbamoyl]cyclopropane-1-carboxylic acid Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1)=CC=C1NC(=O)C1(C(O)=O)CC1 HXGYPQKHBCZWKO-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- IIDUNAVOCYMUFB-UHFFFAOYSA-N 2-amino-5-fluorophenol Chemical compound NC1=CC=C(F)C=C1O IIDUNAVOCYMUFB-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 2
- 201000003076 Angiosarcoma Diseases 0.000 description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
- 206010004146 Basal cell carcinoma Diseases 0.000 description 2
- 206010073106 Bone giant cell tumour malignant Diseases 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 201000005262 Chondroma Diseases 0.000 description 2
- 201000009047 Chordoma Diseases 0.000 description 2
- 206010048832 Colon adenoma Diseases 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 208000006168 Ewing Sarcoma Diseases 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- 206010019629 Hepatic adenoma Diseases 0.000 description 2
- 101000579425 Homo sapiens Proto-oncogene tyrosine-protein kinase receptor Ret Proteins 0.000 description 2
- 208000002404 Liver Cell Adenoma Diseases 0.000 description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 2
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 2
- 208000014767 Myeloproliferative disease Diseases 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- 201000004404 Neurofibroma Diseases 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 102100028286 Proto-oncogene tyrosine-protein kinase receptor Ret Human genes 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 2
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 2
- 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 150000004703 alkoxides Chemical class 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- HFCFMRYTXDINDK-WNQIDUERSA-N cabozantinib malate Chemical compound OC(=O)[C@@H](O)CC(O)=O.C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1)=CC=C1NC(=O)C1(C(=O)NC=2C=CC(F)=CC=2)CC1 HFCFMRYTXDINDK-WNQIDUERSA-N 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 208000006990 cholangiocarcinoma Diseases 0.000 description 2
- 201000005217 chondroblastoma Diseases 0.000 description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 2
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 239000003517 fume Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 208000006359 hepatoblastoma Diseases 0.000 description 2
- 201000002735 hepatocellular adenoma Diseases 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000005040 ion trap Methods 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 201000004593 malignant giant cell tumor Diseases 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 206010027191 meningioma Diseases 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical compound CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 208000003388 osteoid osteoma Diseases 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 208000000649 small cell carcinoma Diseases 0.000 description 2
- 239000012418 sodium perborate tetrahydrate Substances 0.000 description 2
- IBDSNZLUHYKHQP-UHFFFAOYSA-N sodium;3-oxidodioxaborirane;tetrahydrate Chemical group O.O.O.O.[Na+].[O-]B1OO1 IBDSNZLUHYKHQP-UHFFFAOYSA-N 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 108091008578 transmembrane receptors Proteins 0.000 description 2
- 102000027257 transmembrane receptors Human genes 0.000 description 2
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 2
- 208000022271 tubular adenoma Diseases 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 208000009540 villous adenoma Diseases 0.000 description 2
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- WHTYLRLZUGABTR-UHFFFAOYSA-N 1-n'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide Chemical compound C=1C=C(F)C=CC=1NC(=O)C1(C(=O)N)CC1 WHTYLRLZUGABTR-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- VXEQRXJATQUJSN-UHFFFAOYSA-N 4-(6,7-dimethoxyquinolin-4-yl)oxyaniline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC1=CC=C(N)C=C1 VXEQRXJATQUJSN-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- XQYICHLOAMMXKE-UHFFFAOYSA-N 5-amino-2-fluorophenol Chemical compound NC1=CC=C(F)C(O)=C1 XQYICHLOAMMXKE-UHFFFAOYSA-N 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 241000321096 Adenoides Species 0.000 description 1
- 206010001233 Adenoma benign Diseases 0.000 description 1
- 102000004228 Aurora kinase B Human genes 0.000 description 1
- 108090000749 Aurora kinase B Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 208000009458 Carcinoma in Situ Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010039499 Cartilage sarcomas Diseases 0.000 description 1
- 206010008263 Cervical dysplasia Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000005243 Chondrosarcoma Diseases 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 208000000471 Dysplastic Nevus Syndrome Diseases 0.000 description 1
- 206010062805 Dysplastic naevus Diseases 0.000 description 1
- 201000009051 Embryonal Carcinoma Diseases 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 206010014967 Ependymoma Diseases 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 201000006850 Familial medullary thyroid carcinoma Diseases 0.000 description 1
- 208000007659 Fibroadenoma Diseases 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 208000021309 Germ cell tumor Diseases 0.000 description 1
- 208000000527 Germinoma Diseases 0.000 description 1
- 208000007569 Giant Cell Tumors Diseases 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- 201000005409 Gliomatosis cerebri Diseases 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- 208000037196 Medullary thyroid carcinoma Diseases 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010073148 Multiple endocrine neoplasia type 2A Diseases 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 201000010133 Oligodendroglioma Diseases 0.000 description 1
- 208000000035 Osteochondroma Diseases 0.000 description 1
- 208000007641 Pinealoma Diseases 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
- 102000008022 Proto-Oncogene Proteins c-met Human genes 0.000 description 1
- 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 208000005678 Rhabdomyoma Diseases 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- 208000000097 Sertoli-Leydig cell tumor Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000009311 VIPoma Diseases 0.000 description 1
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 206010048215 Xanthomatosis Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 210000002534 adenoid Anatomy 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 210000002821 alveolar epithelial cell Anatomy 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000035578 autophosphorylation Effects 0.000 description 1
- 208000003373 basosquamous carcinoma Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 238000005574 benzylation reaction Methods 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000003149 breast fibroadenoma Diseases 0.000 description 1
- 210000003123 bronchiole Anatomy 0.000 description 1
- 201000002143 bronchus adenoma Diseases 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 238000004517 catalytic hydrocracking Methods 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000009060 clear cell adenocarcinoma Diseases 0.000 description 1
- 229940034568 cometriq Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000008406 drug-drug interaction Effects 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 108091071773 flk family Proteins 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 201000003115 germ cell cancer Diseases 0.000 description 1
- 201000011610 giant cell glioblastoma Diseases 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 208000002409 gliosarcoma Diseases 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 229930182480 glucuronide Natural products 0.000 description 1
- 150000008134 glucuronides Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 201000004933 in situ carcinoma Diseases 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 208000022013 kidney Wilms tumor Diseases 0.000 description 1
- 208000003849 large cell carcinoma Diseases 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 208000030883 malignant astrocytoma Diseases 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 201000000289 malignant teratoma Diseases 0.000 description 1
- 208000026037 malignant tumor of neck Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 208000009091 myxoma Diseases 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 201000008026 nephroblastoma Diseases 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 208000004649 neutrophil actin dysfunction Diseases 0.000 description 1
- 230000000802 nitrating effect Effects 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 208000008798 osteoma Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 208000024724 pineal body neoplasm Diseases 0.000 description 1
- 201000004123 pineal gland cancer Diseases 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000001855 preneoplastic effect Effects 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 201000006845 reticulosarcoma Diseases 0.000 description 1
- 208000029922 reticulum cell sarcoma Diseases 0.000 description 1
- TZSZZENYCISATO-WIOPSUGQSA-N rodatristat Chemical compound CCOC(=O)[C@@H]1CC2(CN1)CCN(CC2)c1cc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)nc(N)n1 TZSZZENYCISATO-WIOPSUGQSA-N 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 201000002314 small intestine cancer Diseases 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- MFXSJHWNOHCFKS-UHFFFAOYSA-M sodium;1-methoxycarbonylcyclopropane-1-carboxylate Chemical compound [Na+].COC(=O)C1(C([O-])=O)CC1 MFXSJHWNOHCFKS-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000017572 squamous cell neoplasm Diseases 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 230000001180 sulfating effect Effects 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 208000001608 teratocarcinoma Diseases 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 208000013818 thyroid gland medullary carcinoma Diseases 0.000 description 1
- 206010044412 transitional cell carcinoma Diseases 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000003905 vulva Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461954352P | 2014-03-17 | 2014-03-17 | |
| US61/954,352 | 2014-03-17 | ||
| PCT/US2015/021072 WO2015142928A1 (en) | 2014-03-17 | 2015-03-17 | Dosing of cabozantinib formulations |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017507995A JP2017507995A (ja) | 2017-03-23 |
| JP2017507995A5 JP2017507995A5 (enExample) | 2018-04-26 |
| JP6666849B2 true JP6666849B2 (ja) | 2020-03-18 |
Family
ID=52811227
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016558004A Active JP6666849B2 (ja) | 2014-03-17 | 2015-03-17 | カボザンチニブ製剤の投与 |
Country Status (7)
| Country | Link |
|---|---|
| US (3) | US10159666B2 (enExample) |
| EP (1) | EP3119476A1 (enExample) |
| JP (1) | JP6666849B2 (enExample) |
| CN (1) | CN106255499A (enExample) |
| EA (1) | EA201691850A1 (enExample) |
| MA (1) | MA39735A (enExample) |
| WO (1) | WO2015142928A1 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW202112751A (zh) | 2009-01-16 | 2021-04-01 | 美商艾克塞里克斯公司 | 包含n-(4-{[6,7-雙(甲氧基)喹啉-4-基]氧基}苯基)-n'-(4-氟苯基)環丙烷-1,1-二甲醯胺之蘋果酸鹽之醫藥組合物及其用途 |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| HUE057574T2 (hu) | 2011-02-10 | 2022-05-28 | Exelixis Inc | Eljárás kinolin-származékok és ilyen vegyületeket tartalmazó gyógyászati készítmények elõállítására |
| NZ712330A (en) | 2013-03-15 | 2020-04-24 | Exelixis Inc | Metabolites of n-(4-{ [6,7-bis(methyloxy)quinolin-4-yl]oxy} phenyl)-n’-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide |
| US11564915B2 (en) | 2013-04-04 | 2023-01-31 | Exelixis, Inc. | Cabozantinib dosage form and use in the treatment of cancer |
| EP3738952A1 (en) | 2014-02-14 | 2020-11-18 | Exelixis, Inc. | Crystalline solid forms of n-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-n'-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide, processes for making, and methods of use |
| EP3119476A1 (en) | 2014-03-17 | 2017-01-25 | Exelixis, Inc. | Dosing of cabozantinib formulations |
| CN106715397B (zh) * | 2014-07-31 | 2021-07-23 | 埃克塞里艾克西斯公司 | 制备氟-18标记的卡博替尼及其类似物的方法 |
| MA40457A (fr) | 2014-08-05 | 2017-06-14 | Exelixis Inc | Combinaison de médicaments pour traiter le myélome multiple |
| WO2016161952A1 (zh) * | 2015-04-07 | 2016-10-13 | 广东众生药业股份有限公司 | 酪氨酸激酶抑制剂及包含该酪氨酸激酶抑制剂的药物组合物 |
| US11141413B2 (en) | 2016-04-15 | 2021-10-12 | Exelixis, Inc. | Method of treating renal cell carcinoma using N-(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, (2S)-hydroxybutanedioate |
| CN107951850A (zh) * | 2017-12-20 | 2018-04-24 | 深圳万乐药业有限公司 | 一种苹果酸卡博替尼片的制备方法 |
| IL321138A (en) | 2018-01-26 | 2025-07-01 | Exelixis Inc | Compounds for the treatment of kinase-dependent disorders |
| CN115192540A (zh) | 2018-06-15 | 2022-10-18 | 汉达癌症医药责任有限公司 | 激酶抑制剂的盐类及其组合物 |
| AU2024215796A1 (en) | 2023-01-31 | 2025-05-15 | Handa Oncology, Llc | Improved cabozantinib compositions and methods of use |
| WO2025079089A1 (en) * | 2023-10-09 | 2025-04-17 | Msn Laboratories Private Limited, R&D Center | Pharmaceutical composition of cabozantinib |
| WO2025196845A1 (en) * | 2024-03-22 | 2025-09-25 | Meishi Pharma Services Pvt. Ltd. | Improved formulations of cabozantinib |
Family Cites Families (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2210607B1 (en) | 2003-09-26 | 2011-08-17 | Exelixis Inc. | N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide for the treatment of cancer |
| US20080161305A1 (en) | 2005-04-06 | 2008-07-03 | Exelixis, Inc. | C-Met Modulators and Methods of Use |
| CN111643496A (zh) | 2006-12-14 | 2020-09-11 | 埃克塞利希斯股份有限公司 | 使用mek抑制剂的方法 |
| UY31800A (es) | 2008-05-05 | 2009-11-10 | Smithkline Beckman Corp | Metodo de tratamiento de cancer usando un inhibidor de cmet y axl y un inhibidor de erbb |
| UY32142A (es) | 2008-09-26 | 2010-05-31 | Smithkline Beckman Corp | Preparación de una quinoliniloxidifenilciclopropanodicarboxamida |
| WO2010056960A1 (en) | 2008-11-13 | 2010-05-20 | Exelixis Inc. | Methods of preparing quinoline derivatives |
| JP2012511017A (ja) | 2008-12-04 | 2012-05-17 | エグゼリクシス， インコーポレイテッド | キノリン誘導体の調製方法 |
| TW202112751A (zh) | 2009-01-16 | 2021-04-01 | 美商艾克塞里克斯公司 | 包含n-(4-{[6,7-雙(甲氧基)喹啉-4-基]氧基}苯基)-n'-(4-氟苯基)環丙烷-1,1-二甲醯胺之蘋果酸鹽之醫藥組合物及其用途 |
| WO2011009095A1 (en) | 2009-07-17 | 2011-01-20 | Exelixis, Inc. | Crystalline forms of n-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]-quin0lin-4-yl}oxy)phenyl]-n'-(4-fluorophenyl)cyclopropane-1, 1-dicarboxamide |
| UA108618C2 (uk) * | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| KR20130038206A (ko) | 2010-03-12 | 2013-04-17 | 엑셀리시스, 인코포레이티드 | Ｎ-〔3-플루오로-4-(｛6-（메틸옥시）-7-〔（3-모폴린-4-일프로필）옥시〕-퀴놀린-4-일｝옥시）페닐〕-ｎ’-（4-플루오로페닐）사이클로프로판-1,1-디카복사미드의 수화된 결정형 형태 |
| US20120070368A1 (en) | 2010-04-16 | 2012-03-22 | Exelixis, Inc. | Methods of Using C-Met Modulators |
| EA030435B1 (ru) | 2010-07-16 | 2018-08-31 | Экселиксис, Инк. | ТАБЛЕТКА, СОДЕРЖАЩАЯ МОДУЛЯТОР c-MET В ФОРМЕ КРИСТАЛЛИЧЕСКОЙ L-МАЛАТНОЙ СОЛИ (ВАРИАНТЫ), СПОСОБ ЕЕ ПРОИЗВОДСТВА И СПОСОБ ЛЕЧЕНИЯ ОНКОЛОГИЧЕСКОГО ЗАБОЛЕВАНИЯ С ЕЕ ИСПОЛЬЗОВАНИЕМ |
| US20140186407A9 (en) | 2010-07-16 | 2014-07-03 | Exelixis Inc. | C-Met Modulator Pharmaceutical Compositions |
| EA027476B1 (ru) | 2010-09-27 | 2017-07-31 | Экселиксис, Инк. | Применение n-(4-{[6,7-бис-(метилокси)хинолин-4-ил]окси}фенил)-n'-(4-фторфенил)циклопропан-1,1-дикарбоксамида для лечения кастрационно-резистентного рака простаты и остеобластических метастазов в кости |
| CA2812744A1 (en) | 2010-09-27 | 2012-04-05 | Exelixis, Inc. | Dual inhibitors of met and vegf for the treatment of castration resistant prostate cancer and osteoblastic bone metastases |
| JP2013540759A (ja) | 2010-09-27 | 2013-11-07 | エクセリクシス， インク． | 去勢抵抗性前立腺癌および造骨性転移の治療のためのｍｅｔおよびｖｅｇｆの二元阻害薬 |
| EP2643001A4 (en) | 2010-11-22 | 2014-02-19 | Glaxosmithkline Ip Dev Ltd | METHOD OF TREATING CANCER |
| HUE057574T2 (hu) | 2011-02-10 | 2022-05-28 | Exelixis Inc | Eljárás kinolin-származékok és ilyen vegyületeket tartalmazó gyógyászati készítmények elõállítására |
| US20120252840A1 (en) | 2011-04-04 | 2012-10-04 | Exelixis, Inc. | Method of Treating Cancer |
| CN103717221A (zh) | 2011-05-02 | 2014-04-09 | 埃克塞里艾克西斯公司 | 治疗癌症和骨癌疼痛的方法 |
| TW201306842A (zh) | 2011-06-15 | 2013-02-16 | Exelixis Inc | 使用ｐｉ３ｋ／ｍｔｏｒ吡啶並嘧啶酮抑制劑及苯達莫司汀及／或利妥昔單抗治療惡性血液疾病之組合療法 |
| CA2848512A1 (en) | 2011-09-22 | 2013-03-28 | Exelixis, Inc. | Method for treating osteoporosis |
| BR112014009302B1 (pt) | 2011-10-20 | 2020-04-28 | Exelis Inc Us/Us | processo para preparar derivados de quinolina |
| CA2854336A1 (en) | 2011-11-08 | 2013-05-16 | Exelixis, Inc. | Dual inhibitor of met and vegf for treating cancer |
| HK1207587A1 (en) | 2012-05-02 | 2016-02-05 | Exelixis, Inc. | A dual met - vegf modulator for treating osteolytic bone metastases |
| CN114129566A (zh) | 2012-09-07 | 2022-03-04 | 埃克塞里艾克西斯公司 | 用于治疗肺腺癌的met、vegfr和ret的抑制剂 |
| US20140221372A1 (en) | 2013-02-06 | 2014-08-07 | GlaxoSmithKline Intellectual Property (NO 2.) Limited | Method of administration and treatment |
| NZ712330A (en) * | 2013-03-15 | 2020-04-24 | Exelixis Inc | Metabolites of n-(4-{ [6,7-bis(methyloxy)quinolin-4-yl]oxy} phenyl)-n’-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide |
| US11564915B2 (en) | 2013-04-04 | 2023-01-31 | Exelixis, Inc. | Cabozantinib dosage form and use in the treatment of cancer |
| MX2015014046A (es) | 2013-04-04 | 2016-05-16 | Exelixis Inc | Combinaciones de farmacos para tratar cancer. |
| EP3738952A1 (en) | 2014-02-14 | 2020-11-18 | Exelixis, Inc. | Crystalline solid forms of n-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-n'-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide, processes for making, and methods of use |
| EP3119476A1 (en) | 2014-03-17 | 2017-01-25 | Exelixis, Inc. | Dosing of cabozantinib formulations |
| EP3906921A1 (en) | 2014-04-25 | 2021-11-10 | Exelixis, Inc. | Method of treating lung adenocarcinoma |
| CN106715397B (zh) | 2014-07-31 | 2021-07-23 | 埃克塞里艾克西斯公司 | 制备氟-18标记的卡博替尼及其类似物的方法 |
| MA40457A (fr) | 2014-08-05 | 2017-06-14 | Exelixis Inc | Combinaison de médicaments pour traiter le myélome multiple |
| WO2016061253A1 (en) | 2014-10-14 | 2016-04-21 | Exelixis, Inc. | Drug combination to treat melanoma |
-
2015
- 2015-03-17 EP EP15714340.5A patent/EP3119476A1/en not_active Withdrawn
- 2015-03-17 WO PCT/US2015/021072 patent/WO2015142928A1/en not_active Ceased
- 2015-03-17 MA MA039735A patent/MA39735A/fr unknown
- 2015-03-17 US US15/126,767 patent/US10159666B2/en active Active
- 2015-03-17 CN CN201580023083.9A patent/CN106255499A/zh active Pending
- 2015-03-17 JP JP2016558004A patent/JP6666849B2/ja active Active
- 2015-03-17 EA EA201691850A patent/EA201691850A1/ru unknown
-
2018
- 2018-11-14 US US16/190,869 patent/US20190076420A1/en not_active Abandoned
-
2020
- 2020-01-29 US US16/776,139 patent/US20200163954A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CN106255499A (zh) | 2016-12-21 |
| US10159666B2 (en) | 2018-12-25 |
| US20200163954A1 (en) | 2020-05-28 |
| WO2015142928A1 (en) | 2015-09-24 |
| EP3119476A1 (en) | 2017-01-25 |
| US20170087143A1 (en) | 2017-03-30 |
| US20190076420A1 (en) | 2019-03-14 |
| EA201691850A1 (ru) | 2016-12-30 |
| MA39735A (fr) | 2017-01-25 |
| JP2017507995A (ja) | 2017-03-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6666849B2 (ja) | カボザンチニブ製剤の投与 | |
| US20240287002A1 (en) | Metabolites of n-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-n'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide | |
| EP2252605B1 (en) | Labelled analogues of halobenzamides as multimodal radiopharmaceuticals and their precursors | |
| JP7622113B2 (ja) | Ｐｓｍａ阻害剤を含有する１８ｆ標識トリアゾール | |
| CN115701991A (zh) | 吡唑基丙酰胺化合物及其用于治疗前列腺癌的用途 | |
| WO2014145693A1 (en) | Metabolites 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 | |
| CN102267952B (zh) | 喹唑啉类化合物、其制备方法和用途 | |
| HK1220447B (en) | Metabolites of n-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-n'-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide | |
| CN111491669A (zh) | 可用于pet和切伦科夫发光成像的18f标记的肽配体 | |
| Morais et al. | Month 2015 Synthesis and Biological Evaluation of Novel 2-Aryl Benzimidazoles as Chemotherapeutic Agents | |
| TW201617077A (zh) | 用以治療及／或預防呼吸器官疾病之醫藥組成物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180316 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180316 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20181206 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190306 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190426 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190606 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190702 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190917 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200218 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200221 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6666849 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |