KR101937704B1 - 2-(2,4,5-치환 아닐린)피리미딘 유도체, 이의 약물 조성물 및 이의 용도 - Google Patents
2-(2,4,5-치환 아닐린)피리미딘 유도체, 이의 약물 조성물 및 이의 용도 Download PDFInfo
- Publication number
- KR101937704B1 KR101937704B1 KR1020177007190A KR20177007190A KR101937704B1 KR 101937704 B1 KR101937704 B1 KR 101937704B1 KR 1020177007190 A KR1020177007190 A KR 1020177007190A KR 20177007190 A KR20177007190 A KR 20177007190A KR 101937704 B1 KR101937704 B1 KR 101937704B1
- Authority
- KR
- South Korea
- Prior art keywords
- cancer
- methyl
- amino
- acid salt
- pharmaceutically acceptable
- 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
- 150000003230 pyrimidines Chemical class 0.000 title claims abstract description 22
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 title claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 11
- 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 title abstract 4
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 239000003814 drug Substances 0.000 claims abstract description 23
- 239000012453 solvate Substances 0.000 claims abstract description 18
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 16
- 201000011510 cancer Diseases 0.000 claims abstract description 8
- 239000000463 material Substances 0.000 claims abstract description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 41
- -1 tri-substituted methyl group Chemical group 0.000 claims description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 229940079593 drug Drugs 0.000 claims description 19
- 150000001448 anilines Chemical class 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 12
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 9
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 8
- 208000032612 Glial tumor Diseases 0.000 claims description 6
- 206010018338 Glioma Diseases 0.000 claims description 6
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 6
- 239000005551 L01XE03 - Erlotinib Substances 0.000 claims description 6
- 206010029260 Neuroblastoma Diseases 0.000 claims description 6
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 6
- 229960001433 erlotinib Drugs 0.000 claims description 6
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 6
- 201000002510 thyroid cancer Diseases 0.000 claims description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical class OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 5
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 5
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 5
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical class CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 claims description 3
- 206010003571 Astrocytoma Diseases 0.000 claims description 3
- 206010005003 Bladder cancer Diseases 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 3
- 206010014733 Endometrial cancer Diseases 0.000 claims description 3
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 3
- 206010027406 Mesothelioma Diseases 0.000 claims description 3
- 208000034578 Multiple myelomas Diseases 0.000 claims description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
- 206010060862 Prostate cancer Diseases 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
- 206010038389 Renal cancer Diseases 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- 208000000728 Thymus Neoplasms Diseases 0.000 claims description 3
- 208000033781 Thyroid carcinoma Diseases 0.000 claims description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 3
- 150000008107 benzenesulfonic acids Chemical class 0.000 claims description 3
- 201000010881 cervical cancer Diseases 0.000 claims description 3
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 3
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 claims description 3
- 201000010536 head and neck cancer Diseases 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
- 201000010982 kidney cancer Diseases 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 201000007270 liver cancer Diseases 0.000 claims description 3
- 208000014018 liver neoplasm Diseases 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 201000002528 pancreatic cancer Diseases 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 201000006845 reticulosarcoma Diseases 0.000 claims description 3
- 208000029922 reticulum cell sarcoma Diseases 0.000 claims description 3
- 201000009377 thymus cancer Diseases 0.000 claims description 3
- 208000013077 thyroid gland carcinoma Diseases 0.000 claims description 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 2
- 239000003798 L01XE11 - Pazopanib Substances 0.000 claims description 2
- 229960000397 bevacizumab Drugs 0.000 claims description 2
- 229960005395 cetuximab Drugs 0.000 claims description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 2
- 229960004316 cisplatin Drugs 0.000 claims description 2
- 229960002949 fluorouracil Drugs 0.000 claims description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 2
- 229960001756 oxaliplatin Drugs 0.000 claims description 2
- 229960000639 pazopanib Drugs 0.000 claims description 2
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 claims description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 4
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 claims 2
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 claims 2
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims 2
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 claims 2
- 229940072107 ascorbate Drugs 0.000 claims 2
- 235000010323 ascorbic acid Nutrition 0.000 claims 2
- 239000011668 ascorbic acid Substances 0.000 claims 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims 2
- 229940077388 benzenesulfonate Drugs 0.000 claims 2
- 229940044170 formate Drugs 0.000 claims 2
- 229940050411 fumarate Drugs 0.000 claims 2
- 229940050410 gluconate Drugs 0.000 claims 2
- 229940097042 glucuronate Drugs 0.000 claims 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims 2
- 229960001860 salicylate Drugs 0.000 claims 2
- 229940071182 stannate Drugs 0.000 claims 2
- 125000005402 stannate group Chemical group 0.000 claims 2
- 150000003460 sulfonic acids Chemical class 0.000 claims 2
- FAKFSJNVVCGEEI-UHFFFAOYSA-J tin(4+);disulfate Chemical compound [Sn+4].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O FAKFSJNVVCGEEI-UHFFFAOYSA-J 0.000 claims 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims 2
- 229910000096 monohydride Inorganic materials 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 19
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 abstract description 4
- 108010017384 Blood Proteins Proteins 0.000 abstract description 2
- 102000004506 Blood Proteins Human genes 0.000 abstract description 2
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- 230000000259 anti-tumor effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 238000012360 testing method Methods 0.000 description 25
- 102000001301 EGF receptor Human genes 0.000 description 20
- 108060006698 EGF receptor Proteins 0.000 description 20
- 239000000203 mixture Substances 0.000 description 18
- 229960003278 osimertinib Drugs 0.000 description 18
- DUYJMQONPNNFPI-UHFFFAOYSA-N osimertinib Chemical compound COC1=CC(N(C)CCN(C)C)=C(NC(=O)C=C)C=C1NC1=NC=CC(C=2C3=CC=CC=C3N(C)C=2)=N1 DUYJMQONPNNFPI-UHFFFAOYSA-N 0.000 description 18
- 239000007787 solid Substances 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 15
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 239000000376 reactant Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 8
- 229920002472 Starch Polymers 0.000 description 7
- 125000004431 deuterium atom Chemical group 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 239000008107 starch Substances 0.000 description 7
- 235000019698 starch Nutrition 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- JSYBAZQQYCNZJE-UHFFFAOYSA-N benzene-1,2,4-triamine Chemical compound NC1=CC=C(N)C(N)=C1 JSYBAZQQYCNZJE-UHFFFAOYSA-N 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 230000004614 tumor growth Effects 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000012065 filter cake Substances 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 230000002440 hepatic effect Effects 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000002207 metabolite Substances 0.000 description 4
- 210000001589 microsome Anatomy 0.000 description 4
- 238000011580 nude mouse model Methods 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000005995 Aluminium silicate Substances 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 102000003992 Peroxidases Human genes 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 235000012211 aluminium silicate Nutrition 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 235000019864 coconut oil Nutrition 0.000 description 3
- 239000003240 coconut oil Substances 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 238000001647 drug administration Methods 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 239000012089 stop solution Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- BLRHMMGNCXNXJL-UHFFFAOYSA-N 1-methylindole Chemical compound C1=CC=C2N(C)C=CC2=C1 BLRHMMGNCXNXJL-UHFFFAOYSA-N 0.000 description 2
- BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
- IIBWXYHPBMUNJP-UHFFFAOYSA-N 3-(2-chloropyrimidin-4-yl)-1-methylindole Chemical compound C12=CC=CC=C2N(C)C=C1C1=CC=NC(Cl)=N1 IIBWXYHPBMUNJP-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 241000512259 Ascophyllum nodosum Species 0.000 description 2
- SFSGCHNQJUPDRK-UHFFFAOYSA-N CC1(C=CC(NC2=NC=CC(C3=C(C)NC4=CC=CC=C34)=N2)=CC1N)N Chemical compound CC1(C=CC(NC2=NC=CC(C3=C(C)NC4=CC=CC=C34)=N2)=CC1N)N SFSGCHNQJUPDRK-UHFFFAOYSA-N 0.000 description 2
- 0 CN(C)CCN(C)c(c(NC(C=C)=O)c1)cc(OC(*)(*)*)c1Nc1nccc(-c2c[n](C)c3ccccc23)n1 Chemical compound CN(C)CCN(C)c(c(NC(C=C)=O)c1)cc(OC(*)(*)*)c1Nc1nccc(-c2c[n](C)c3ccccc23)n1 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical class OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007942 layered tablet Substances 0.000 description 2
- 239000006194 liquid suspension Substances 0.000 description 2
- 210000005265 lung cell Anatomy 0.000 description 2
- IBIKHMZPHNKTHM-RDTXWAMCSA-N merck compound 25 Chemical compound C1C[C@@H](C(O)=O)[C@H](O)CN1C(C1=C(F)C=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C1CC1 IBIKHMZPHNKTHM-RDTXWAMCSA-N 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 210000003370 receptor cell Anatomy 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 229960003604 testosterone Drugs 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical class OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- CBCKQZAAMUWICA-UHFFFAOYSA-N 1,4-phenylenediamine Chemical compound NC1=CC=C(N)C=C1 CBCKQZAAMUWICA-UHFFFAOYSA-N 0.000 description 1
- SWWQQSDRUYSMAR-UHFFFAOYSA-N 1-[(4-hydroxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-diol;hydrochloride Chemical group Cl.C1=CC(O)=CC=C1CC1C2=CC(O)=C(O)C=C2CCN1 SWWQQSDRUYSMAR-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- YXYUGWUUQKSUCB-UHFFFAOYSA-N 4-[4-(1-methylindol-3-yl)pyrimidin-2-yl]cyclohexa-1,5-diene-1,2,4-triamine Chemical compound CN1C=C(C2=CC=CC=C12)C1=NC(=NC=C1)C1(CC(=C(C=C1)N)N)N YXYUGWUUQKSUCB-UHFFFAOYSA-N 0.000 description 1
- FYSIGSQCZXQTIH-UHFFFAOYSA-N 4-fluoro-2-methoxy-5-nitroaniline Chemical compound COC1=CC(F)=C([N+]([O-])=O)C=C1N FYSIGSQCZXQTIH-UHFFFAOYSA-N 0.000 description 1
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 239000005711 Benzoic acid Chemical class 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical class OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical class OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 1
- XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical class O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Chemical class OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- IHJFCKMAQSYVJG-UHFFFAOYSA-N dichloromethane iodomethane Chemical class IC.ClCCl IHJFCKMAQSYVJG-UHFFFAOYSA-N 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 150000002314 glycerols Chemical class 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960004891 lapatinib Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000001853 liver microsome Anatomy 0.000 description 1
- 230000007056 liver toxicity Effects 0.000 description 1
- 208000018883 loss of balance Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000001630 malic acid Chemical class 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZFRKQXVRDFCRJG-UHFFFAOYSA-N skatole Chemical compound C1=CC=C2C(C)=CNC2=C1 ZFRKQXVRDFCRJG-UHFFFAOYSA-N 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- QHGNHLZPVBIIPX-UHFFFAOYSA-N tin(ii) oxide Chemical class [Sn]=O QHGNHLZPVBIIPX-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410401604.7A CN104140418B (zh) | 2014-08-15 | 2014-08-15 | 2-(2，4，5-取代苯胺)嘧啶衍生物及其用途 |
| CN201410401604.7 | 2014-08-15 | ||
| PCT/CN2015/085714 WO2016023422A1 (zh) | 2014-08-15 | 2015-07-31 | 2-(2,4,5-取代苯胺)嘧啶衍生物、其药物组合物及其用途 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20170036107A KR20170036107A (ko) | 2017-03-31 |
| KR101937704B1 true KR101937704B1 (ko) | 2019-01-14 |
Family
ID=51849768
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020177007190A Active KR101937704B1 (ko) | 2014-08-15 | 2015-07-31 | 2-(2,4,5-치환 아닐린)피리미딘 유도체, 이의 약물 조성물 및 이의 용도 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US10414756B2 (enExample) |
| EP (1) | EP3181559B8 (enExample) |
| JP (1) | JP6418622B2 (enExample) |
| KR (1) | KR101937704B1 (enExample) |
| CN (1) | CN104140418B (enExample) |
| AU (1) | AU2015303641B2 (enExample) |
| CA (1) | CA2958095C (enExample) |
| WO (1) | WO2016023422A1 (enExample) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104140418B (zh) * | 2014-08-15 | 2016-08-24 | 常州润诺生物科技有限公司 | 2-(2，4，5-取代苯胺)嘧啶衍生物及其用途 |
| CN105237515B (zh) * | 2014-10-10 | 2018-06-05 | 益方生物科技（上海）有限公司 | 氘代嘧啶类化合物、其制备方法、药物组合物和用途 |
| SI3205650T1 (sl) | 2014-10-11 | 2021-10-29 | Shanghai Hansoh Biomedical Co Ltd | Zaviralec EGFR-ja in priprava ter uporaba le-tega |
| CN105085489B (zh) | 2014-11-05 | 2019-03-01 | 益方生物科技（上海）有限公司 | 嘧啶或吡啶类化合物、其制备方法和医药用途 |
| CN105712998B (zh) * | 2014-12-05 | 2019-12-13 | 上海润诺生物科技有限公司 | 氮杂吲哚类衍生物、其制备方法及其在医药上的应用 |
| CN105001208A (zh) * | 2015-08-06 | 2015-10-28 | 南京雷科星生物技术有限公司 | 一种表皮生长因子受体egfr抑制剂及其制备方法与用途 |
| CN105153122B (zh) * | 2015-08-27 | 2018-07-20 | 上海圣考医药科技有限公司 | [(吲哚-3-基)嘧啶-2-基]氨基苯基丙-2-烯酰胺衍生物及盐、制备方法、应用 |
| KR102051609B1 (ko) * | 2015-08-31 | 2019-12-03 | 우시 상량 바이오테크놀로지 씨오., 엘티디. | 2-아릴아미노피리딘, 피리미딘 또는 트리아진 유도체 및 그 제조방법과 사용 |
| CN110483485A (zh) * | 2015-09-02 | 2019-11-22 | 益方生物科技（上海）有限公司 | 嘧啶类化合物、其制备方法和医药用途 |
| AU2016380190B2 (en) * | 2015-12-27 | 2019-03-14 | NeuForm Pharmaceuticals, Inc. | Deuterated compounds for treating cancer and related diseases and conditions, and compositions and methods thereof |
| CN108610331A (zh) * | 2016-01-22 | 2018-10-02 | 焦玉奇 | 2-(2,4,5-取代苯胺)嘧啶衍生物 |
| CN107043369A (zh) * | 2016-02-06 | 2017-08-15 | 焦玉奇 | 2‑(2,4,5‑取代苯胺)嘧啶衍生物 |
| JP7007287B2 (ja) * | 2016-03-22 | 2022-01-24 | ジエンス ハンセン ファーマセウティカル グループ カンパニー リミテッド | Ｅｇｆｒ阻害薬フリー塩基または酸性塩の多結晶形、その製造方法、および応用 |
| EP3464275B1 (en) | 2016-05-26 | 2024-05-08 | Recurium IP Holdings, LLC | Egfr inhibitor compounds |
| US10654851B2 (en) * | 2016-09-19 | 2020-05-19 | Nanjing Chuangte Pharmaceutical Technology Co., Ltd. | Deuterated 3-(4,5-substituted aminopyrimidine)phenyl derivatives and use thereof |
| CN108129342A (zh) * | 2016-11-30 | 2018-06-08 | 浙江九洲药物科技有限公司 | 一种奥希替尼中间体及其制备方法 |
| CN108047205B (zh) * | 2016-12-14 | 2019-08-27 | 河南真实生物科技有限公司 | 2-(2，4，5-取代苯氨基)嘧啶衍生物、其制备方法及其在制备抗肿瘤药物中的应用 |
| CN106957304B (zh) * | 2017-04-25 | 2017-12-01 | 孔令廷 | 一种石墨烯负载FeCl3催化剂的制备方法及其在制备抗癌药物中间体的用途 |
| CN107192773B (zh) * | 2017-05-17 | 2019-09-27 | 张家港威胜生物医药有限公司 | 一种检测奥希替尼含量和有关物质的高效液相法 |
| CN108929311B (zh) * | 2017-05-22 | 2020-07-28 | 焦玉奇 | 2-(2,4,5-取代苯胺)嘧啶衍生物 |
| CN108558835B (zh) * | 2017-05-24 | 2024-08-16 | 浙江同源康医药股份有限公司 | 一种氘代azd9291的晶型、制备方法及用途 |
| WO2019001425A1 (zh) * | 2017-06-27 | 2019-01-03 | 浙江同源康医药股份有限公司 | 一种氘代奥斯替尼衍生物及其应用 |
| TWI702205B (zh) * | 2017-10-06 | 2020-08-21 | 俄羅斯聯邦商拜奧卡德聯合股份公司 | 表皮生長因子受體抑制劑 |
| CN107954918B (zh) * | 2017-11-30 | 2022-01-25 | 郑州泰基鸿诺医药股份有限公司 | 一种n-氘代甲基吲哚类化合物的合成方法 |
| CN108047207A (zh) * | 2018-01-30 | 2018-05-18 | 天津大学 | N-[5-(嘧啶-2-氨基)-2,4-二取代苯基]-2-氟代丙烯酰胺氘代物及应用 |
| CN110272420A (zh) * | 2018-03-16 | 2019-09-24 | 江苏正大丰海制药有限公司 | 氘代3-(4,5-取代氨基嘧啶)苯基化合物单甲磺酸盐晶型及其制备方法 |
| CN110950847B (zh) * | 2018-09-27 | 2022-11-01 | 浙江同源康医药股份有限公司 | 氘代azd9291化合物的新晶型及其用途 |
| CN110003183A (zh) * | 2019-04-09 | 2019-07-12 | 河南真实生物科技有限公司 | 2-（2，4，5-取代苯氨基）嘧啶衍生物及其晶形b |
| CN111909135A (zh) * | 2020-08-15 | 2020-11-10 | 天津大学 | 一种azd9291氘代物甲磺酸盐新盐型及其制备方法 |
| WO2022146201A1 (en) * | 2020-12-30 | 2022-07-07 | Joint Stock Company "Biocad" | Epidermal growth factor receptor inhibitors |
| CN113387935B (zh) * | 2021-07-23 | 2022-06-10 | 苏州雅深智慧科技有限公司 | 抑制三突变表皮生长因子受体酪氨酸激酶的化合物及用途 |
| CN113582976B (zh) * | 2021-08-24 | 2023-03-17 | 郑州大学 | 氘代2-取代苯胺-4-吲哚基嘧啶类衍生物及其制备方法和应用 |
| WO2025092926A1 (zh) * | 2023-10-31 | 2025-05-08 | 浙江同源康医药股份有限公司 | 一种嘧啶类衍生物的药物组合物 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013014448A1 (en) * | 2011-07-27 | 2013-01-31 | Astrazeneca Ab | 2 - (2, 4, 5 - substituted -anilino) pyrimidine derivatives as egfr modulators useful for treating cancer |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012502038A (ja) | 2008-09-03 | 2012-01-26 | テバ ファーマシューティカル インダストリーズ リミティド | 免疫機能の２−オキソ−１，２−ジヒドロ−キノリンモジュレーター |
| CN101676266B (zh) * | 2008-09-19 | 2011-10-26 | 苏州泽璟生物制药有限公司 | 氘代的ω-二苯基脲及衍生物以及包含该化合物的药物组合物 |
| CN104140418B (zh) * | 2014-08-15 | 2016-08-24 | 常州润诺生物科技有限公司 | 2-(2，4，5-取代苯胺)嘧啶衍生物及其用途 |
-
2014
- 2014-08-15 CN CN201410401604.7A patent/CN104140418B/zh active Active
-
2015
- 2015-07-31 EP EP15832588.6A patent/EP3181559B8/en active Active
- 2015-07-31 KR KR1020177007190A patent/KR101937704B1/ko active Active
- 2015-07-31 US US15/553,892 patent/US10414756B2/en active Active
- 2015-07-31 JP JP2017527959A patent/JP6418622B2/ja active Active
- 2015-07-31 CA CA2958095A patent/CA2958095C/en active Active
- 2015-07-31 WO PCT/CN2015/085714 patent/WO2016023422A1/zh not_active Ceased
- 2015-07-31 AU AU2015303641A patent/AU2015303641B2/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013014448A1 (en) * | 2011-07-27 | 2013-01-31 | Astrazeneca Ab | 2 - (2, 4, 5 - substituted -anilino) pyrimidine derivatives as egfr modulators useful for treating cancer |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2015303641A1 (en) | 2017-03-23 |
| CN104140418B (zh) | 2016-08-24 |
| US10414756B2 (en) | 2019-09-17 |
| US20180016258A1 (en) | 2018-01-18 |
| WO2016023422A1 (zh) | 2016-02-18 |
| CA2958095C (en) | 2023-09-26 |
| AU2015303641B2 (en) | 2018-04-12 |
| EP3181559A1 (en) | 2017-06-21 |
| EP3181559A4 (en) | 2017-06-21 |
| KR20170036107A (ko) | 2017-03-31 |
| CN104140418A (zh) | 2014-11-12 |
| JP2017523247A (ja) | 2017-08-17 |
| JP6418622B2 (ja) | 2018-11-07 |
| EP3181559B8 (en) | 2018-11-14 |
| EP3181559B1 (en) | 2018-10-03 |
| CA2958095A1 (en) | 2016-02-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101937704B1 (ko) | 2-(2,4,5-치환 아닐린)피리미딘 유도체, 이의 약물 조성물 및 이의 용도 | |
| US12049460B2 (en) | EGFR inhibitor compounds | |
| USRE49556E1 (en) | Compounds and compositions as protein kinase inhibitors | |
| CA3087089C (en) | Fused ring compounds | |
| JP6945015B2 (ja) | Ｎ２，ｎ４−ジフェニルピリミジン−２，４−ジアミン誘導体、その製造方法、およびこれを有効成分として含む癌の予防または治療用の薬学的組成物 | |
| ES3000079T3 (en) | 2,4-disubstituted pyrimidine derivative, preparation method for same, and uses thereof | |
| BR112012011287A2 (pt) | compostos inibidores de cinase, sua formulação farmacêutica e seus usos | |
| KR20180098361A (ko) | 아실아닐리드 유도체, 이의 제조 방법 및 약학에서의 적용 | |
| EP3697416A1 (en) | Inhibitors of mutant egfr family tyrosine-kinases | |
| KR20220128590A (ko) | 암세포 성장 억제 효과를 나타내는 신규한 피리미딘 유도체 | |
| HK40003936A (en) | Egfr inhibitor compounds | |
| HK1167390B (en) | Compounds and compositions as protein kinase inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| PA0105 | International application |
Patent event date: 20170315 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PA0201 | Request for examination | ||
| PG1501 | Laying open of application | ||
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20180416 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20181018 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20190107 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20190108 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| PR1001 | Payment of annual fee |
Payment date: 20220103 Start annual number: 4 End annual number: 4 |