CN1134438C - 二环杂芳族化合物、其制备方法以及用途 - Google Patents
二环杂芳族化合物、其制备方法以及用途 Download PDFInfo
- Publication number
- CN1134438C CN1134438C CNB998038873A CN99803887A CN1134438C CN 1134438 C CN1134438 C CN 1134438C CN B998038873 A CNB998038873 A CN B998038873A CN 99803887 A CN99803887 A CN 99803887A CN 1134438 C CN1134438 C CN 1134438C
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- China
- Prior art keywords
- phenyl
- amine
- methyl
- benzyloxy
- methylsulfonyl
- 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.)
- Expired - Lifetime
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- -1 Bicyclic heteroaromatic compounds Chemical class 0.000 title claims abstract description 296
- 239000005483 tyrosine kinase inhibitor Substances 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 177
- 238000002360 preparation method Methods 0.000 claims abstract description 116
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 93
- 150000003839 salts Chemical class 0.000 claims abstract description 64
- 239000012453 solvate Substances 0.000 claims abstract description 54
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000001257 hydrogen Substances 0.000 claims abstract description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 21
- 239000003814 drug Substances 0.000 claims abstract description 7
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims abstract description 5
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 3
- 125000001475 halogen functional group Chemical group 0.000 claims abstract 10
- 150000001875 compounds Chemical class 0.000 claims description 198
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 77
- 239000001301 oxygen Substances 0.000 claims description 51
- 229910052760 oxygen Inorganic materials 0.000 claims description 51
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 49
- 150000002240 furans Chemical group 0.000 claims description 41
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 34
- 230000000694 effects Effects 0.000 claims description 30
- 238000011282 treatment Methods 0.000 claims description 29
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 24
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 24
- 201000010099 disease Diseases 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 239000003153 chemical reaction reagent Substances 0.000 claims description 20
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 14
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 14
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
- 230000014509 gene expression Effects 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 238000006073 displacement reaction Methods 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 239000003981 vehicle Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- HQHSVSSDBPWQBD-UHFFFAOYSA-N n-(3-bromo-4-phenylmethoxyphenyl)-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2N=CC3=NC=NC(NC=4C=C(Br)C(OCC=5C=CC=CC=5)=CC=4)=C3C=2)=C1 HQHSVSSDBPWQBD-UHFFFAOYSA-N 0.000 claims description 2
- PSLPNMRXSBQHQB-UHFFFAOYSA-N n-(3-bromo-4-phenylmethoxyphenyl)-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]quinazolin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2C=C3C(NC=4C=C(Br)C(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)=C1 PSLPNMRXSBQHQB-UHFFFAOYSA-N 0.000 claims description 2
- AXVKGZLOECWENV-UHFFFAOYSA-N n-(3-chloro-4-phenylmethoxyphenyl)-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]quinazolin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2C=C3C(NC=4C=C(Cl)C(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)=C1 AXVKGZLOECWENV-UHFFFAOYSA-N 0.000 claims description 2
- RPBYFFUZCIDSBL-UHFFFAOYSA-N n-(3-fluoro-4-phenylmethoxyphenyl)-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2N=CC3=NC=NC(NC=4C=C(F)C(OCC=5C=CC=CC=5)=CC=4)=C3C=2)=C1 RPBYFFUZCIDSBL-UHFFFAOYSA-N 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims 17
- 239000011737 fluorine Substances 0.000 claims 17
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 14
- 230000002682 anti-psoriatic effect Effects 0.000 claims 1
- 229940030999 antipsoriatics Drugs 0.000 claims 1
- LPHALCCJJMLFMZ-UHFFFAOYSA-N n-(3-chloro-4-phenylmethoxyphenyl)-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2N=CC3=NC=NC(NC=4C=C(Cl)C(OCC=5C=CC=CC=5)=CC=4)=C3C=2)=C1 LPHALCCJJMLFMZ-UHFFFAOYSA-N 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 abstract description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 21
- 150000002431 hydrogen Chemical class 0.000 abstract description 15
- 229910052720 vanadium Inorganic materials 0.000 abstract description 7
- 229910052736 halogen Inorganic materials 0.000 abstract description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 abstract description 4
- 150000002367 halogens Chemical class 0.000 abstract description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 4
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 3
- 150000002390 heteroarenes Chemical class 0.000 abstract description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 abstract description 2
- 229930192474 thiophene Natural products 0.000 abstract description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 abstract 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 2
- 125000001041 indolyl group Chemical group 0.000 abstract 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 abstract 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 113
- 239000007787 solid Substances 0.000 description 88
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 82
- 239000002585 base Substances 0.000 description 81
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Substances O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 75
- 239000000203 mixture Substances 0.000 description 72
- 150000001412 amines Chemical class 0.000 description 67
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 62
- 238000006243 chemical reaction Methods 0.000 description 60
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 54
- 238000005160 1H NMR spectroscopy Methods 0.000 description 52
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
- 239000000047 product Substances 0.000 description 39
- 239000000243 solution Substances 0.000 description 39
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 38
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- 238000003756 stirring Methods 0.000 description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 31
- 125000005843 halogen group Chemical group 0.000 description 31
- 239000002904 solvent Substances 0.000 description 29
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
- 125000001153 fluoro group Chemical group F* 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 23
- 125000004122 cyclic group Chemical group 0.000 description 22
- 238000005406 washing Methods 0.000 description 22
- 238000000746 purification Methods 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 21
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 20
- 238000001914 filtration Methods 0.000 description 19
- 150000003254 radicals Chemical class 0.000 description 19
- BDAIUOPDSRAOKI-UHFFFAOYSA-N 4-chloro-6-iodoquinazoline Chemical compound C1=C(I)C=C2C(Cl)=NC=NC2=C1 BDAIUOPDSRAOKI-UHFFFAOYSA-N 0.000 description 18
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000012141 concentrate Substances 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 16
- 235000008504 concentrate Nutrition 0.000 description 16
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 14
- 125000001309 chloro group Chemical group Cl* 0.000 description 14
- 101150028321 Lck gene Proteins 0.000 description 13
- 239000003513 alkali Substances 0.000 description 13
- 238000004440 column chromatography Methods 0.000 description 13
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- 238000001291 vacuum drying Methods 0.000 description 13
- 239000007788 liquid Substances 0.000 description 12
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- 238000001556 precipitation Methods 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 229910052799 carbon Inorganic materials 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 11
- 238000010898 silica gel chromatography Methods 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
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- 239000012074 organic phase Substances 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical group C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 9
- 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 9
- 230000026731 phosphorylation Effects 0.000 description 9
- 238000006366 phosphorylation reaction Methods 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 108060006698 EGF receptor Proteins 0.000 description 8
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 8
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
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- 230000000903 blocking effect Effects 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 125000004175 fluorobenzyl group Chemical group 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
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- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 7
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- 239000000284 extract Substances 0.000 description 7
- 229910052740 iodine Inorganic materials 0.000 description 7
- 239000011630 iodine Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000000376 reactant Substances 0.000 description 7
- DZSDPGLVFIHJMM-UHFFFAOYSA-N 2-methylsulfonyl-N-[(2-pyridin-2-yl-1,3-thiazol-4-yl)methyl]ethanamine Chemical compound CS(=O)(=O)CCNCC1=CSC(C=2N=CC=CC=2)=N1 DZSDPGLVFIHJMM-UHFFFAOYSA-N 0.000 description 6
- BRYNKBKRYHGHEL-UHFFFAOYSA-N 2-methylsulfonyl-N-[(2-pyridin-2-yl-1,3-thiazol-5-yl)methyl]ethanamine Chemical compound CS(=O)(=O)CCNCC1=CN=C(S1)C2=CC=CC=N2 BRYNKBKRYHGHEL-UHFFFAOYSA-N 0.000 description 6
- RKPBTXCXXLRIRP-UHFFFAOYSA-N 2-methylsulfonyl-N-[(3-pyridin-2-ylphenyl)methyl]ethanamine Chemical compound CS(=O)(=O)CCNCC1=CC=CC(=C1)C1=CC=CC=N1 RKPBTXCXXLRIRP-UHFFFAOYSA-N 0.000 description 6
- JUIZKGUHSBVPJF-UHFFFAOYSA-N 2-methylsulfonyl-N-[(4-pyridin-2-yl-1,3-thiazol-2-yl)methyl]ethanamine Chemical compound CS(=O)(=O)CCNCC1=NC(=CS1)C2=CC=CC=N2 JUIZKGUHSBVPJF-UHFFFAOYSA-N 0.000 description 6
- LSQAKMULRDHVJL-UHFFFAOYSA-N 2-methylsulfonyl-N-[(4-pyridin-2-ylphenyl)methyl]ethanamine Chemical compound CS(=O)(=O)CCNCC1=CC=C(C=C1)C2=CC=CC=N2 LSQAKMULRDHVJL-UHFFFAOYSA-N 0.000 description 6
- RCNGMZLBOJMNAD-UHFFFAOYSA-N 2-methylsulfonyl-N-[(5-pyridin-2-yl-1,3-thiazol-2-yl)methyl]ethanamine Chemical compound CS(=O)(=O)CCNCC1=NC=C(S1)C2=CC=CC=N2 RCNGMZLBOJMNAD-UHFFFAOYSA-N 0.000 description 6
- GYGVLTPJGBTTPG-UHFFFAOYSA-N 2-methylsulfonyl-N-[(5-pyridin-2-ylfuran-3-yl)methyl]ethanamine Chemical compound CS(=O)(=O)CCNCC1=COC(=C1)C2=CC=CC=N2 GYGVLTPJGBTTPG-UHFFFAOYSA-N 0.000 description 6
- AULWPXHFRBLPAE-UHFFFAOYSA-N 6-chloropyridine Chemical compound ClC1=C=CC=C[N]1 AULWPXHFRBLPAE-UHFFFAOYSA-N 0.000 description 6
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- 208000026310 Breast neoplasm Diseases 0.000 description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
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- 230000008020 evaporation Effects 0.000 description 6
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- 238000004128 high performance liquid chromatography Methods 0.000 description 6
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- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 6
- IVDNIDWMJHKOSW-UHFFFAOYSA-N n-(furan-2-ylmethyl)-2-methylsulfonylethanamine Chemical compound CS(=O)(=O)CCNCC1=CC=CO1 IVDNIDWMJHKOSW-UHFFFAOYSA-N 0.000 description 6
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- KRFXKLWWUDJFJY-UHFFFAOYSA-N 4-chloro-7-fluoro-6-iodoquinazoline Chemical compound C1=NC(Cl)=C2C=C(I)C(F)=CC2=N1 KRFXKLWWUDJFJY-UHFFFAOYSA-N 0.000 description 5
- FIIDVVUUWRJXLF-UHFFFAOYSA-N 4-phenylmethoxyaniline Chemical compound C1=CC(N)=CC=C1OCC1=CC=CC=C1 FIIDVVUUWRJXLF-UHFFFAOYSA-N 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 5
- 102000007624 ZAP-70 Protein-Tyrosine Kinase Human genes 0.000 description 5
- 108010046882 ZAP-70 Protein-Tyrosine Kinase Proteins 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 5
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
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- 230000002829 reductive effect Effects 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
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- HHTDXGKATRNJNN-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-7-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]quinolin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC(C=2C=C3N=CC=C(NC=4C=CC(OCC=5C=CC(F)=CC=5)=CC=4)C3=CC=2)=C1 HHTDXGKATRNJNN-UHFFFAOYSA-N 0.000 description 1
- SBDCLCNNXTXHPV-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-7-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-5-yl]quinolin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=NC=C1C1=CC=C(C(NC=2C=CC(OCC=3C=CC(F)=CC=3)=CC=2)=CC=N2)C2=C1 SBDCLCNNXTXHPV-UHFFFAOYSA-N 0.000 description 1
- QMHPOCQSOCGYSK-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-7-[3-[(2-methylsulfonylethylamino)methyl]phenyl]quinolin-4-amine Chemical compound CS(=O)(=O)CCNCC1=CC=CC(C=2C=C3N=CC=C(NC=4C=CC(OCC=5C=CC(F)=CC=5)=CC=4)C3=CC=2)=C1 QMHPOCQSOCGYSK-UHFFFAOYSA-N 0.000 description 1
- KRZZVRMYWQYYJM-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-7-[4-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-2-yl]quinazolin-4-amine Chemical compound CS(=O)(=O)CCNCC1=CSC(C=2C=C3N=CN=C(NC=4C=CC(OCC=5C=CC(F)=CC=5)=CC=4)C3=CC=2)=N1 KRZZVRMYWQYYJM-UHFFFAOYSA-N 0.000 description 1
- GJHIKSULQNFIKA-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-7-[4-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound CS(=O)(=O)CCNCC1=COC(C=2C=C3N=CN=C(NC=4C=CC(OCC=5C=CC(F)=CC=5)=CC=4)C3=CC=2)=C1 GJHIKSULQNFIKA-UHFFFAOYSA-N 0.000 description 1
- FCLXRHSNORHBDH-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-7-[4-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinolin-4-amine Chemical compound CS(=O)(=O)CCNCC1=COC(C=2C=C3N=CC=C(NC=4C=CC(OCC=5C=CC(F)=CC=5)=CC=4)C3=CC=2)=C1 FCLXRHSNORHBDH-UHFFFAOYSA-N 0.000 description 1
- KYFYZBVHYXQLFU-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-7-[4-[(2-methylsulfonylethylamino)methyl]phenyl]quinolin-4-amine Chemical compound C1=CC(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(C(NC=2C=CC(OCC=3C=CC(F)=CC=3)=CC=2)=CC=N2)C2=C1 KYFYZBVHYXQLFU-UHFFFAOYSA-N 0.000 description 1
- PGYYIPWAUCETBU-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-7-[5-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-2-yl]quinazolin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=CN=C1C1=CC=C(C(NC=2C=CC(OCC=3C=CC(F)=CC=3)=CC=2)=NC=N2)C2=C1 PGYYIPWAUCETBU-UHFFFAOYSA-N 0.000 description 1
- FKSMCCLFZLTWPR-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-7-[5-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-2-yl]quinolin-4-amine Chemical compound S1C(CNCCS(=O)(=O)C)=CN=C1C1=CC=C(C(NC=2C=CC(OCC=3C=CC(F)=CC=3)=CC=2)=CC=N2)C2=C1 FKSMCCLFZLTWPR-UHFFFAOYSA-N 0.000 description 1
- JZARILKSTIILFY-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-7-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(C(NC=2C=CC(OCC=3C=CC(F)=CC=3)=CC=2)=NC=N2)C2=C1 JZARILKSTIILFY-UHFFFAOYSA-N 0.000 description 1
- XWJQFSZZXBAJKO-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-7-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(C(NC=2C=CC(OCC=3C=CC(F)=CC=3)=CC=2)=CC=N2)C2=C1 XWJQFSZZXBAJKO-UHFFFAOYSA-N 0.000 description 1
- JLVLBDODYLEYOY-UHFFFAOYSA-N n-phenylpyrimidin-4-amine Chemical class C=1C=NC=NC=1NC1=CC=CC=C1 JLVLBDODYLEYOY-UHFFFAOYSA-N 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 229940026778 other chemotherapeutics in atc Drugs 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- SMPAPEKFGLKOIC-UHFFFAOYSA-N oxolane;hydrochloride Chemical compound Cl.C1CCOC1 SMPAPEKFGLKOIC-UHFFFAOYSA-N 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
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- 239000003182 parenteral nutrition solution Substances 0.000 description 1
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- QQVIHTHCMHWDBS-UHFFFAOYSA-N perisophthalic acid Natural products OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 description 1
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- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000007715 potassium iodide Nutrition 0.000 description 1
- 229960004839 potassium iodide Drugs 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical compound C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 description 1
- 150000008518 pyridopyrimidines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910000108 silver(I,III) oxide Inorganic materials 0.000 description 1
- 235000011182 sodium carbonates Nutrition 0.000 description 1
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- PODWXQQNRWNDGD-UHFFFAOYSA-L sodium thiosulfate pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[O-]S([S-])(=O)=O PODWXQQNRWNDGD-UHFFFAOYSA-L 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 229940120293 vaginal suppository Drugs 0.000 description 1
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- 230000004862 vasculogenesis Effects 0.000 description 1
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Classifications
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- 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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C07D411/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D411/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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Abstract
Description
底物磷酸化作用 | ||
实施例 | erbB2-测定(b) | EGF-r-测定(a) |
1 | +++ | +++ |
2 | +++ | +++ |
3 | +++ | +++ |
4 | ++ | +++ |
5 | +++ | +++ |
6 | ++ | |
7 | +++ | +++ |
底物磷酸化作用 | |
实施例 | erbB2-测定(b) |
8 | +++ |
9 | +++ |
10 | +++ |
11 | +++ |
12 | ++ |
13 | ++ |
14 | +++ |
15 | +++ |
16 | +++ |
17 | +++ |
18 | +++ |
19 | +++ |
20 | +++ |
21 | +++ |
22 | +++ |
23 | +++ |
24 | +++ |
25 | +++ |
26 | +++ |
27 | +++ |
28 | +++ |
29 | +++ |
33 | +++ |
34 | +++ |
35 | +++ |
36 | +++ |
37 | +++ |
IC50值 | 符号 |
<0.10μM | +++ |
0.10-1.0μM | ++ |
1.0-10.0μM | + |
>10.0μM | - |
未测定 | ND |
底物磷酸化作用 | ||
实施例 | lck | ZAP-70 |
30 | ++ | ++ |
31 | ++ | ++ |
32 | + | + |
IC50值 | 符号 |
0.01-0.10μM | ++ |
0.10-1.0μM | + |
未测定 | ND |
实施例 | 细胞增殖 | ||||
HB4a etnB2 | HB4a ras | BT474 | HN5 | N87 | |
1 | +++ | + | +++ | +++ | +++ |
2 | +++ | + | +++ | +++ | +++ |
3 | +++ | + | +++ | +++ | +++ |
4 | +++ | - | +++ | +++ | +++ |
5 | +++ | - | +++ | +++ | +++ |
6 | +++ | + | +++ | +++ | +++ |
7 | +++ | ++ | +++ | +++ | +++ |
8 | +++ | ++ | +++ | +++ | +++ |
9 | +++ | ++ | +++ | +++ | +++ |
10 | +++ | ++ | +++ | +++ | +++ |
11 | +++ | - | +++ | +++ | +++ |
12 | +++ | - | +++ | ++ | +++ |
13 | ++ | - | ++ | + | ++ |
14 | +++ | - | +++ | +++ | +++ |
15 | +++ | - | +++ | +++ | +++ |
16 | +++ | ++ | +++ | +++ | +++ |
17 | ++ | ++ | +++ | ++ | ++ |
18 | +++ | ++ | +++ | +++ | +++ |
19 | +++ | - | +++ | +++ | +++ |
20 | +++ | - | +++ | ++ | +++ |
21 | +++ | ++ | +++ | +++ | +++ |
22 | +++ | + | +++ | +++ | +++ |
23 | +++ | + | +++ | +++ | +++ |
24 | ++ | - | ++ | +++ | ++ |
25 | +++ | - | +++ | +++ | +++ |
26 | +++ | ++ | +++ | +++ | +++ |
27 | +++ | ++ | +++ | +++ | +++ |
28 | +++ | + | +++ | +++ | +++ |
29 | +++ | - | +++ | +++ | +++ |
33 | +++ | +++ | +++ | +++ | +++ |
34 | +++ | - | +++ | +++ | +++ |
35 | +++ | + | +++ | +++ | +++ |
36 | ++ | - | ++ | ++ | ++ |
37 | +++ | + | +++ | +++ | +++ |
IC50值 | 符号 |
<5μM | +++ |
5-25μM | ++ |
25-50μM | + |
>50μM | - |
未测定 | ND |
Claims (22)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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GB9800569.7 | 1998-01-12 | ||
GBGB9800569.7A GB9800569D0 (en) | 1998-01-12 | 1998-01-12 | Heterocyclic compounds |
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CN1292788A CN1292788A (zh) | 2001-04-25 |
CN1134438C true CN1134438C (zh) | 2004-01-14 |
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CNB998038873A Expired - Lifetime CN1134438C (zh) | 1998-01-12 | 1999-01-08 | 二环杂芳族化合物、其制备方法以及用途 |
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Cited By (5)
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Families Citing this family (410)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6294532B1 (en) | 1997-08-22 | 2001-09-25 | Zeneca Limited | Oxindolylquinazoline derivatives as angiogenesis inhibitors |
RS49779B (sr) * | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
PT1119567E (pt) | 1998-10-08 | 2005-08-31 | Astrazeneca Ab | Derivados de quinazolina |
GB2345486A (en) * | 1999-01-11 | 2000-07-12 | Glaxo Group Ltd | Heteroaromatic protein tyrosine kinase inhibitors |
PL205557B1 (pl) | 1999-02-10 | 2010-05-31 | Astrazeneca Ab | Pochodne indolu |
GB9910579D0 (en) | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
GB9910580D0 (en) | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
UA71976C2 (en) | 1999-06-21 | 2005-01-17 | Boehringer Ingelheim Pharma | Bicyclic heterocycles and a medicament based thereon |
US6933299B1 (en) | 1999-07-09 | 2005-08-23 | Smithkline Beecham Corporation | Anilinoquinazolines as protein tyrosine kinase inhibitors |
AU5783300A (en) * | 1999-07-09 | 2001-01-30 | Glaxo Group Limited | Anilinoquinazolines as protein tyrosine kinase inhibitors |
BR0014116A (pt) * | 1999-09-21 | 2002-05-21 | Astrazeneca Ab | Uso de um composto, composto, métodos para preparação de um composto, e para inibir aurora 2 quinase em um animal de sangue quente, e, composição farmacêutica |
UA74803C2 (uk) | 1999-11-11 | 2006-02-15 | Осі Фармасьютікалз, Інк. | Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування |
JP2003520855A (ja) * | 2000-01-28 | 2003-07-08 | アストラゼネカ アクチボラグ | 化学的化合物 |
GB0002952D0 (en) * | 2000-02-09 | 2000-03-29 | Pharma Mar Sa | Process for producing kahalalide F compounds |
US6521618B2 (en) | 2000-03-28 | 2003-02-18 | Wyeth | 3-cyanoquinolines, 3-cyano-1,6-naphthyridines, and 3-cyano-1,7-naphthyridines as protein kinase inhibitors |
AR035851A1 (es) * | 2000-03-28 | 2004-07-21 | Wyeth Corp | 3-cianoquinolinas, 3-ciano-1,6-naftiridinas y 3-ciano-1,7-naftiridinas como inhibidoras de proteina quinasas |
US6462238B2 (en) | 2000-05-02 | 2002-10-08 | Array Biopharma, Inc. | Process for the reduction of cyano-substituted sulfones to aminoalkylene-substituted sulfones |
MXPA02012870A (es) | 2000-06-22 | 2003-05-14 | Pfizer Prod Inc | Derivados biciclicos sustituidos para el tratamiento del crecimiento celular anormal. |
PL360439A1 (en) | 2000-06-28 | 2004-09-06 | Astrazeneca Ab | Substituted quinazoline derivatives and their use as inhibitors |
EP1792902A1 (en) * | 2000-06-30 | 2007-06-06 | Glaxo Group Limited | Processes for preparation of 5-(6-quinazolinyl)-furan-2-carbaldehydes |
BR0111947A (pt) * | 2000-06-30 | 2003-05-06 | Glaxo Group Ltd | Composto, composição farmacêutica, método para o tratamento de um distúrbio em um mamìfero, uso de um composto e processo para preparar, um composto |
WO2002012226A1 (en) | 2000-08-09 | 2002-02-14 | Astrazeneca Ab | Quinoline derivatives having vegf inhibiting activity |
CA2422488A1 (en) | 2000-09-20 | 2002-03-28 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | 4-amino-quinazolines |
DE60134679D1 (de) | 2000-10-20 | 2008-08-14 | Eisai R&D Man Co Ltd | Stickstoff enthaltende aromatische Heterozyklen |
US7776315B2 (en) | 2000-10-31 | 2010-08-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and additional active ingredients |
WO2002036570A1 (en) | 2000-11-02 | 2002-05-10 | Astrazeneca Ab | 4-substituted quinolines as antitumor agents |
WO2002044166A1 (en) | 2000-11-02 | 2002-06-06 | Astrazeneca Ab | Substituted quinolines as antitumor agents |
US7019012B2 (en) | 2000-12-20 | 2006-03-28 | Boehringer Ingelheim International Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
PE20020801A1 (es) | 2001-01-05 | 2002-09-06 | Pfizer | Anticuerpos contra el receptor del factor de crecimiento similar a insulina |
JP4458746B2 (ja) * | 2001-01-16 | 2010-04-28 | グラクソ グループ リミテッド | 癌の治療方法 |
EP1488809A1 (en) | 2001-01-16 | 2004-12-22 | Glaxo Group Limited | Pharmaceutical combination containing a 4-quinazolineamine and another anti-neoplastic agent for the treatment of cancer |
US6812251B2 (en) * | 2001-03-15 | 2004-11-02 | Rhode Island Hospital | Taurine compounds |
DK1370552T3 (da) * | 2001-03-23 | 2007-05-07 | Bayer Pharmaceuticals Corp | Rho-kinase-inhibitorer |
CA2441492C (en) * | 2001-03-23 | 2011-08-09 | Bayer Corporation | Rho-kinase inhibitors |
EP1249451B1 (en) | 2001-04-13 | 2006-06-21 | Pfizer Products Inc. | Bicyclic-substituted 4-amino-pyridopyrimidine derivatives |
WO2002092578A1 (en) * | 2001-05-14 | 2002-11-21 | Astrazeneca Ab | Quinazoline derivatives |
AU2002345792A1 (en) | 2001-06-21 | 2003-01-08 | Pfizer Inc. | Thienopyridine and thienopyrimidine anticancer agents |
US20090197852A9 (en) * | 2001-08-06 | 2009-08-06 | Johnson Robert G Jr | Method of treating breast cancer using 17-AAG or 17-AG or a prodrug of either in combination with a HER2 inhibitor |
US7829566B2 (en) | 2001-09-17 | 2010-11-09 | Werner Mederski | 4-amino-quinazolines |
AR039067A1 (es) | 2001-11-09 | 2005-02-09 | Pfizer Prod Inc | Anticuerpos para cd40 |
ES2305435T3 (es) | 2002-01-10 | 2008-11-01 | Bayer Healthcare Ag | Inhibidores de la rho-quinasa. |
EP1471910A2 (en) | 2002-01-17 | 2004-11-03 | Neurogen Corporation | Substituted quinazolin-4-ylamine analogues as modulators of capsaicin receptors |
CA2473910C (en) | 2002-01-23 | 2011-03-15 | Bayer Pharmaceuticals Corporation | Pyrimidine derivatives as rho-kinase inhibitors |
MXPA04007191A (es) | 2002-01-23 | 2005-03-31 | Bayer Pharmaceuticals Corp | Derivados de pirimidina como inhibidores de rho-quinasa. |
RU2362774C1 (ru) | 2002-02-01 | 2009-07-27 | Астразенека Аб | Хиназолиновые соединения |
AU2003207291A1 (en) * | 2002-02-06 | 2003-09-02 | Ube Industries, Ltd. | Process for producing 4-aminoquinazoline compound |
EP1492568A1 (en) * | 2002-04-08 | 2005-01-05 | SmithKline Beecham Corporation | Cancer treatment method comprising administration of an erb-family inhibitor and a raf and/or ras inhibitor |
DE10221018A1 (de) | 2002-05-11 | 2003-11-27 | Boehringer Ingelheim Pharma | Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie |
WO2003101491A1 (fr) * | 2002-06-03 | 2003-12-11 | Mitsubishi Pharma Corporation | Moyens preventifs et/ou therapeutiques destines a des sujets presentant l'expression ou l'activation de her2 et/ou egfr |
UA77303C2 (en) | 2002-06-14 | 2006-11-15 | Pfizer | Derivatives of thienopyridines substituted by benzocondensed heteroarylamide useful as therapeutic agents, pharmaceutical compositions and methods for their use |
US20040048887A1 (en) * | 2002-07-09 | 2004-03-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and EGFR kinase inhibitors |
JP2005536486A (ja) | 2002-07-09 | 2005-12-02 | アストラゼネカ アクチボラグ | 癌の処置に使用するためのキナゾリン誘導体 |
GB0215823D0 (en) | 2002-07-09 | 2002-08-14 | Astrazeneca Ab | Quinazoline derivatives |
ES2400339T3 (es) | 2002-07-15 | 2013-04-09 | Symphony Evolution, Inc. | Compuestos, composiciones farmacéuticas de los mismos y su uso en el tratamiento del cáncer |
GB0304367D0 (en) * | 2003-02-26 | 2003-04-02 | Pharma Mar Sau | Methods for treating psoriasis |
GB0225579D0 (en) | 2002-11-02 | 2002-12-11 | Astrazeneca Ab | Chemical compounds |
TWI229650B (en) * | 2002-11-19 | 2005-03-21 | Sharp Kk | Substrate accommodating tray |
BR0317168A (pt) * | 2002-12-13 | 2005-11-01 | Neurogen Corp | Composto ou uma forma farmaceuticamente aceitável do mesmo, composição farmacêutica, métodos de reduzir condutância de cálcio de um receptor de capsaicina celular, e de inibir ligação de ligante vanilóide a um receptor de capsaicina, métodos de tratar uma condição responsiva à modulação de receptor de capsaicina, dor, coceira, tosse ou soluços, incontinência urinária, de promover perda de peso em paciente, e de determinar a presença ou ausência de receptor de capsaicina em uma amostra, preparação farmacêutica embalada, e, uso de um composto |
JP3814285B2 (ja) | 2002-12-19 | 2006-08-23 | ファイザー・インク | 眼疾患の治療に有用なプロテインキナーゼ阻害剤としての2−(1h−インダゾール−6−イルアミノ)−ベンズアミド化合物 |
AU2003292435A1 (en) * | 2002-12-23 | 2004-07-14 | Astrazeneca Ab | 4- (pyridin-4-ylamino) -quinazoline derivatives as anti-tumor agents |
US20060167026A1 (en) * | 2003-01-06 | 2006-07-27 | Hiroyuki Nawa | Antipsychotic molecular-targeting epithelial growth factor receptor |
US7223749B2 (en) | 2003-02-20 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
NZ541861A (en) | 2003-02-26 | 2009-05-31 | Sugen Inc | Aminoheteroaryl compounds as protein kinase inhibitors |
MXPA05012939A (es) | 2003-05-30 | 2006-05-17 | Astrazeneca Uk Ltd | Procedimiento. |
TW200510373A (en) | 2003-07-14 | 2005-03-16 | Neurogen Corp | Substituted quinolin-4-ylamine analogues |
US7329664B2 (en) | 2003-07-16 | 2008-02-12 | Neurogen Corporation | Substituted (7-pyridyl-4-phenylamino-quinazolin-2-yl)-methanol analogues |
NZ544797A (en) | 2003-07-18 | 2011-04-29 | Amgen Fremont Inc | Specific antibodies that bind HGF and neutralise binding of HGF to met |
WO2005011607A2 (en) | 2003-08-01 | 2005-02-10 | Smithkline Beecham Corporation | Treatment of cancers expressing p95 erbb2 |
JP2007504122A (ja) | 2003-08-29 | 2007-03-01 | ファイザー・インク | 新規抗血管形成剤として有用なチエノピリジン−フェニルアセトアミドおよびその誘導体 |
GB0321066D0 (en) * | 2003-09-09 | 2003-10-08 | Pharma Mar Sau | New antitumoral compounds |
AR045563A1 (es) | 2003-09-10 | 2005-11-02 | Warner Lambert Co | Anticuerpos dirigidos a m-csf |
EP2609919A3 (en) * | 2003-09-26 | 2014-02-26 | Exelixis, Inc. | c-Met modulators and methods of use |
DE10349113A1 (de) | 2003-10-17 | 2005-05-12 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung von Aminocrotonylverbindungen |
EP1682123A1 (en) * | 2003-11-07 | 2006-07-26 | SmithKline Beecham (Cork) Limited | Cancer treatment method |
EP1683785B1 (en) | 2003-11-11 | 2013-10-16 | Eisai R&D Management Co., Ltd. | Urea derivative and process for producing the same |
GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
EA013904B1 (ru) * | 2003-12-18 | 2010-08-30 | Янссен Фармацевтика Н.В. | Пиридо- и пиримидопиримидиновые производные в качестве антипролиферативных агентов |
GB0330002D0 (en) | 2003-12-24 | 2004-01-28 | Astrazeneca Ab | Quinazoline derivatives |
WO2005105094A2 (en) * | 2004-04-16 | 2005-11-10 | Smithkline Beecham Corporation | Cancer treatment method |
AU2005239878B9 (en) | 2004-05-06 | 2010-01-07 | Warner-Lambert Company Llc | 4-phenylamino-quinazolin-6-yl-amides |
JP2008501690A (ja) * | 2004-06-03 | 2008-01-24 | スミスクライン ビーチャム (コーク) リミテッド | がんの治療方法 |
EP1781293A1 (en) * | 2004-06-04 | 2007-05-09 | Amphora Discovery Corporation | Quinoline- and isoquinoline-based compounds exhibiting atp-utilizing enzyme inhibitory activity, and compositions, and uses thereof |
BRPI0511765A (pt) * | 2004-06-04 | 2008-01-08 | Smithkline Beechman Cork Ltd | métodos de tratar cáncer de mama, de pulmão, e colo-retal em um mamìfero |
US20100226931A1 (en) * | 2004-06-24 | 2010-09-09 | Nicholas Valiante | Compounds for immunopotentiation |
EP2277595A3 (en) | 2004-06-24 | 2011-09-28 | Novartis Vaccines and Diagnostics, Inc. | Compounds for immunopotentiation |
US20060035893A1 (en) | 2004-08-07 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders |
PL1786785T3 (pl) | 2004-08-26 | 2010-08-31 | Pfizer | Enancjomerycznie czyste związki aminoheteroarylowe jako kinazy białkowe |
ES2322175T3 (es) | 2004-09-17 | 2009-06-17 | EISAI R&D MANAGEMENT CO., LTD. | Composicion medicinal con estabilidad mejorada y gelificacion reducida. |
TW200621251A (en) | 2004-10-12 | 2006-07-01 | Neurogen Corp | Substituted biaryl quinolin-4-ylamine analogues |
US7652009B2 (en) | 2004-11-30 | 2010-01-26 | Amgem Inc. | Substituted heterocycles and methods of use |
GB0427131D0 (en) * | 2004-12-10 | 2005-01-12 | Glaxosmithkline Biolog Sa | Novel combination |
ATE501148T1 (de) | 2004-12-14 | 2011-03-15 | Astrazeneca Ab | Pyrazolopyrimidinverbindungen als antitumormittel |
EP1824492B1 (en) * | 2004-12-17 | 2013-07-10 | SmithKline Beecham (Cork) Limited | Lapatinib for treating breast cancer brain metastases |
US7812022B2 (en) | 2004-12-21 | 2010-10-12 | Glaxosmithkline Llc | 2-pyrimidinyl pyrazolopyridine ErbB kinase inhibitors |
WO2006068826A2 (en) * | 2004-12-21 | 2006-06-29 | Smithkline Beecham Corporation | 2-pyrimidinyl pyrazolopyridine erbb kinase inhibitors |
PE20060777A1 (es) | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas |
CA2593482A1 (en) * | 2005-01-14 | 2006-07-20 | Neurogen Corporation | Heteroaryl substituted quinolin-4-ylamine analogues |
LT3248600T (lt) | 2005-02-18 | 2020-07-27 | Abraxis Bioscience, Llc | Terapinių agentų deriniai bei įvedimo būdai ir kombinuotas gydymas |
US8735394B2 (en) | 2005-02-18 | 2014-05-27 | Abraxis Bioscience, Llc | Combinations and modes of administration of therapeutic agents and combination therapy |
US20060216288A1 (en) * | 2005-03-22 | 2006-09-28 | Amgen Inc | Combinations for the treatment of cancer |
EP1863848A4 (en) | 2005-03-31 | 2009-09-23 | Agensys Inc | CORRESPONDING ANTIBODIES AND MOLECULES THAT ATTACH PROTEINS 161P2F10B |
BRPI0609962B1 (pt) | 2005-04-19 | 2022-01-18 | Novartis Ag | Composição farmacêutica oral |
MX2007013304A (es) | 2005-04-26 | 2007-12-13 | Pfizer | Anticuerpos de p-caderina. |
JP4989476B2 (ja) | 2005-08-02 | 2012-08-01 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 血管新生阻害物質の効果を検定する方法 |
PL2447283T3 (pl) | 2005-09-07 | 2015-12-31 | Amgen Fremont Inc | Ludzkie przeciwciała monoklonalne przeciwko kinazie podobnej do receptora aktywiny-1 (ALK-1) |
ES2374450T3 (es) | 2005-09-20 | 2012-02-16 | OSI Pharmaceuticals, LLC | Marcadores biológicos predictivos de respuesta anticancerígena para inhibidores de cinasa del receptor del factor de crecimiento 1 similar a insulina. |
DE602006018331D1 (de) | 2005-09-20 | 2010-12-30 | Astrazeneca Ab | 4-(1h-indazol-5-ylamino)chinazolinverbindungen als inhibitoren der erbb-rezeptortyrosinkinase zur behandlung von krebs |
UA96139C2 (uk) | 2005-11-08 | 2011-10-10 | Дженентек, Інк. | Антитіло до нейропіліну-1 (nrp1) |
EP1948179A1 (en) | 2005-11-11 | 2008-07-30 | Boehringer Ingelheim International GmbH | Quinazoline derivatives for the treatment of cancer diseases |
ES2421450T3 (es) * | 2005-12-05 | 2013-09-02 | Glaxosmithkline Llc | 2-Pirimidinil-pirazolopiridinas inhibidoras de la quinasa ErbB |
JO2660B1 (en) | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
CN101003514A (zh) * | 2006-01-20 | 2007-07-25 | 上海艾力斯医药科技有限公司 | 喹唑啉衍生物、其制备方法及用途 |
AR059066A1 (es) * | 2006-01-27 | 2008-03-12 | Amgen Inc | Combinaciones del inhibidor de la angiopoyetina -2 (ang2) y el inhibidor del factor de crecimiento endotelial vascular (vegf) |
AU2007211684A1 (en) * | 2006-01-31 | 2007-08-09 | F. Hoffmann-La Roche Ag | 7H-pyrido[3,4-d]pyrimidin-8-ones, their manufacture and use as protein kinase inhibitors |
PE20070978A1 (es) * | 2006-02-14 | 2007-11-15 | Novartis Ag | COMPUESTOS HETEROCICLICOS COMO INHIBIDORES DE FOSFATIDILINOSITOL 3-QUINASAS (PI3Ks) |
TW200808739A (en) * | 2006-04-06 | 2008-02-16 | Novartis Vaccines & Diagnostic | Quinazolines for PDK1 inhibition |
US20090203718A1 (en) * | 2006-04-13 | 2009-08-13 | Smithkline Beecham (Cork) Ltd. | Cancer treatment method |
CA2648809A1 (en) | 2006-04-19 | 2007-11-01 | Novartis Ag | Indazole compounds and methods for inhibition of cdc7 |
MEP43308A (en) | 2006-05-09 | 2011-02-10 | Pfizer Prod Inc | Cycloalkylamino acid derivatives and pharmaceutical compositions thereof |
NL2000613C2 (nl) | 2006-05-11 | 2007-11-20 | Pfizer Prod Inc | Triazoolpyrazinederivaten. |
WO2007136103A1 (ja) | 2006-05-18 | 2007-11-29 | Eisai R & D Management Co., Ltd. | 甲状腺癌に対する抗腫瘍剤 |
EP1862802B1 (en) * | 2006-06-01 | 2008-12-10 | Cellzome Ag | Methods for the identification of ZAP-70 interacting molecules and for the purification of ZAP-70 |
EP2032989B2 (en) | 2006-06-30 | 2015-10-28 | Merck Sharp & Dohme Corp. | Igfbp2 biomarker |
US8217177B2 (en) | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
PE20080403A1 (es) | 2006-07-14 | 2008-04-25 | Amgen Inc | Derivados heterociclicos fusionados y metodos de uso |
US20080051422A1 (en) * | 2006-08-22 | 2008-02-28 | Concert Pharmaceuticals Inc. | 4-Aminoquinazoline derivatives and methods of use thereof |
US20110053964A1 (en) * | 2006-08-22 | 2011-03-03 | Roger Tung | 4-aminoquinazoline derivatives and methods of use thereof |
WO2008026748A1 (fr) | 2006-08-28 | 2008-03-06 | Eisai R & D Management Co., Ltd. | Agent antitumoral pour cancer gastrique non différencié |
PT2068880E (pt) | 2006-09-18 | 2012-07-12 | Boehringer Ingelheim Int | Método para tratamento do cancro apresentando mutações no egfr |
JP2010505811A (ja) * | 2006-10-04 | 2010-02-25 | ファイザー・プロダクツ・インク | カルシウム受容体アンタゴニストとしてのピリド[4,3−d]ピリミジン−4(3H)−オン誘導体 |
EP2073807A1 (en) | 2006-10-12 | 2009-07-01 | Astex Therapeutics Limited | Pharmaceutical combinations |
US8916552B2 (en) | 2006-10-12 | 2014-12-23 | Astex Therapeutics Limited | Pharmaceutical combinations |
WO2008054633A1 (en) * | 2006-10-31 | 2008-05-08 | Janssen Pharmaceutica N.V. | Hydrazone derivatives as kinase inhibitors |
WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
AU2007334456A1 (en) | 2006-12-13 | 2008-06-26 | Merck Sharp & Dohme Corp. | Methods of cancer treatment with IGF1R inhibitors |
EP2125781A2 (en) | 2006-12-20 | 2009-12-02 | Amgen Inc. | Substituted heterocycles and methods of use |
ES2449482T3 (es) | 2007-01-09 | 2014-03-19 | Amgen Inc. | Derivados de bis-aril-amida útiles para el tratamiento de cáncer |
KR101445892B1 (ko) | 2007-01-29 | 2014-09-29 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 미분화형 위암 치료용 조성물 |
CN101245050A (zh) * | 2007-02-14 | 2008-08-20 | 上海艾力斯医药科技有限公司 | 4-苯胺喹唑啉衍生物的盐 |
JP2010519204A (ja) | 2007-02-16 | 2010-06-03 | アムジエン・インコーポレーテツド | 窒素含有複素環ケトン類およびそれらのc−Met阻害薬としての使用 |
EP2076289B1 (en) | 2007-04-13 | 2014-11-12 | Dana-Farber Cancer Institute, Inc. | Methods for treating cancer resistant to erbb therapeutics |
KR20090130347A (ko) * | 2007-05-09 | 2009-12-22 | 화이자 인코포레이티드 | 치환된 헤테로사이클릭 유도체 및 조성물 및 항균제로서의 이의 약학적 용도 |
WO2008154469A1 (en) * | 2007-06-11 | 2008-12-18 | Smithkline Beecham (Cork) Limited | Quinazoline salt compounds |
UY31137A1 (es) * | 2007-06-14 | 2009-01-05 | Smithkline Beecham Corp | Derivados de quinazolina como inhibidores de la pi3 quinasa |
SI2188313T1 (en) | 2007-08-21 | 2018-04-30 | Amgen, Inc. | HUMAN C-FMS ANTIGEN TRANSFER PROTEIN |
CA2698287A1 (en) | 2007-09-07 | 2009-03-12 | Agensys, Inc. | Antibodies and related molecules that bind to 24p4c12 proteins |
US20090215802A1 (en) * | 2007-09-13 | 2009-08-27 | Protia, Llc | Deuterium-enriched lapatinib |
EP2207561A2 (en) * | 2007-10-19 | 2010-07-21 | Pharma Mar, S.A. | Improved antitumoral treatments |
WO2009055343A2 (en) | 2007-10-22 | 2009-04-30 | Schering Corporation | Fully human anti-vegf antibodies and methods of using |
JP2011502141A (ja) | 2007-10-29 | 2011-01-20 | ナトコ ファーマ リミテッド | 抗癌剤としての4‐(テトラゾール‐5‐イル)‐キナゾリン誘導体 |
US8952035B2 (en) | 2007-11-09 | 2015-02-10 | Eisai R&D Management Co., Ltd. | Combination of anti-angiogenic substance and anti-tumor platinum complex |
CA2710122A1 (en) | 2007-12-20 | 2009-07-02 | Novartis Ag | Thiazole derivatives used as pi 3 kinase inhibitors |
CN101492445A (zh) * | 2008-01-22 | 2009-07-29 | 孙飘扬 | 杂芳族化合物、其制备方法以及其用途 |
EP2252315A1 (en) * | 2008-01-30 | 2010-11-24 | Pharma Mar, S.A. | Improved antitumoral treatments |
WO2009109649A1 (en) * | 2008-03-07 | 2009-09-11 | Pharma Mar, S.A. | Improved antitumoral treatments |
EP3692988A3 (en) | 2008-03-18 | 2020-10-14 | Genentech, Inc. | Combinations of an anti-her2 antibody-drug conjugate and 5-fu, anti-vegf antibody, carboplatin or abt-869 and methods of use |
WO2009137714A2 (en) * | 2008-05-07 | 2009-11-12 | Teva Pharmaceutical Industries Ltd. | Forms of lapatinib ditosylate and processes for preparation thereof |
US20090306106A1 (en) * | 2008-05-15 | 2009-12-10 | Leonid Metsger | Forms of crystalline lapatinib and processes for preparation thereof |
CN101584696A (zh) | 2008-05-21 | 2009-11-25 | 上海艾力斯医药科技有限公司 | 包含喹唑啉衍生物的组合物及制备方法、用途 |
US20100197915A1 (en) * | 2008-08-06 | 2010-08-05 | Leonid Metsger | Lapatinib intermediates |
EP2158913A1 (en) | 2008-08-25 | 2010-03-03 | Ratiopharm GmbH | Pharmaceutical composition comprising N-[3-chhloro-4-[(3-fluorophenyl)methoxy]phenyl]6-(5[[[2-(methylsulfonyl)ethyl]amino]methyl]-2-furyl]-4-quinazolinamine |
EP2158912A1 (en) | 2008-08-25 | 2010-03-03 | Ratiopharm GmbH | Pharmaceutical composition comprising N-[3-chhloro-4-[3-fluorophenyl)methoxy)phenyl]6-[5[[[2-(methylsulfonyl)ethyl]amino]methyl]-2-furyl]-4-quinazolinamine |
US20100087459A1 (en) * | 2008-08-26 | 2010-04-08 | Leonid Metsger | Forms of lapatinib compounds and processes for the preparation thereof |
US8476410B2 (en) | 2008-10-16 | 2013-07-02 | University of Pittsburgh—of the Commonwealth System of Higher Education | Fully human antibodies to high molecular weight-melanoma associated antigen and uses thereof |
CA2740977A1 (en) | 2008-11-03 | 2010-06-03 | Natco Pharma Limited | A novel process for the preparation of lapatinib and its pharmaceutically acceptable salts |
MX2011004824A (es) | 2008-11-07 | 2012-01-12 | Triact Therapeutics Inc | Uso de derivados de butano catecólico en terapia contra el cáncer. |
TW202241853A (zh) | 2009-01-16 | 2022-11-01 | 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 |
CN102307875A (zh) | 2009-02-09 | 2012-01-04 | 苏伯俭股份有限公司 | 吡咯并嘧啶基axl激酶抑制剂 |
US20120189641A1 (en) | 2009-02-25 | 2012-07-26 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
EP2400990A2 (en) | 2009-02-26 | 2012-01-04 | OSI Pharmaceuticals, LLC | In situ methods for monitoring the emt status of tumor cells in vivo |
JP2012519281A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ,エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
JP2012519282A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ,エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
WO2010098866A1 (en) | 2009-02-27 | 2010-09-02 | Supergen, Inc. | Cyclopentathiophene/cyclohexathiophene dna methyltransferase inhibitors |
WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
EP2403339B1 (en) | 2009-03-06 | 2017-01-18 | Merck Sharp & Dohme Corp. | Combination cancer therapy with an akt inhibitor and other anticancer agents |
US20120064072A1 (en) | 2009-03-18 | 2012-03-15 | Maryland Franklin | Combination Cancer Therapy Comprising Administration of an EGFR Inhibitor and an IGF-1R Inhibitor |
MY152068A (en) | 2009-03-20 | 2014-08-15 | Genentech Inc | Bispecific anti-her antibodies |
WO2010120388A1 (en) | 2009-04-17 | 2010-10-21 | Nektar Therapeutics | Oligomer-protein tyrosine kinase inhibitor conjugates |
US8530492B2 (en) | 2009-04-17 | 2013-09-10 | Nektar Therapeutics | Oligomer-protein tyrosine kinase inhibitor conjugates |
US8293753B2 (en) | 2009-07-02 | 2012-10-23 | Novartis Ag | Substituted 2-carboxamide cycloamino ureas |
HUE044629T2 (hu) | 2009-07-06 | 2019-11-28 | Boehringer Ingelheim Int | Eljárás BIBW2992, annak sói, valamint e hatóanyagot tartalmazó szilárd gyógyászati készítmények szárítására |
UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
ES2589377T3 (es) | 2009-08-21 | 2016-11-14 | Novartis Ag | Lapatinib para el tratamiento del cáncer |
EP2473500A2 (en) | 2009-09-01 | 2012-07-11 | Pfizer Inc. | Benzimidazole derivatives |
US20120245351A1 (en) * | 2009-09-29 | 2012-09-27 | Natco Pharma Limited | Process for the preparation of lapatinib and its pharmaceutically acceptable salts |
WO2011058164A1 (en) | 2009-11-13 | 2011-05-19 | Pangaea Biotech, S.A. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
CN102079759B (zh) * | 2009-12-01 | 2014-09-17 | 天津药物研究院 | 6位取代的喹唑啉类衍生物、其制备方法和用途 |
AR079256A1 (es) | 2009-12-04 | 2012-01-04 | Genentech Inc | Metodo para el tratamiento del cancer de mama metastasico con trastuzumab-mcc-dm1 |
CN102791715B (zh) | 2009-12-31 | 2016-04-27 | 卡洛斯三世国家癌症研究中心基金会 | 用作激酶抑制剂的三环化合物 |
CA2787714C (en) | 2010-01-22 | 2019-04-09 | Joaquin Pastor Fernandez | Inhibitors of pi3 kinase |
CN104876937B (zh) | 2010-02-12 | 2017-07-28 | 辉瑞公司 | 8‑氟‑2‑{4‑[(甲氨基)甲基]苯基}‑1,3,4,5‑四氢‑6H‑氮杂*并[5,4,3‑cd]吲哚‑6‑酮的马来酸盐、其药物组合物及其用途 |
WO2011101644A1 (en) | 2010-02-18 | 2011-08-25 | Centro Nacional De Investigaciones Oncologicas (Cnio) | Triazolo [4, 5 - b] pyridin derivatives |
US20110275644A1 (en) | 2010-03-03 | 2011-11-10 | Buck Elizabeth A | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
EP2542893A2 (en) | 2010-03-03 | 2013-01-09 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
TWI453202B (zh) * | 2010-03-23 | 2014-09-21 | Scinopharm Taiwan Ltd | 製備拉帕替尼之方法及中間體 |
US8710221B2 (en) | 2010-03-23 | 2014-04-29 | Scinopharm Taiwan, Ltd. | Process and intermediates for preparing lapatinib |
AU2011232862B2 (en) | 2010-03-29 | 2016-03-03 | Abraxis Bioscience, Llc | Methods of enhancing drug delivery and effectiveness of therapeutic agents |
SG10201906075VA (en) | 2010-03-29 | 2019-08-27 | Abraxis Bioscience Llc | Methods of treating cancer |
WO2011121317A1 (en) | 2010-04-01 | 2011-10-06 | Centro Nacional De Investigaciones Oncologicas (Cnio) | Imidazo [2,1-b] [1,3,4] thiadiazoles as protein or lipid kinase inhibitors |
US20130072507A1 (en) | 2010-05-21 | 2013-03-21 | Glaxosmithkline Llc | Combination |
ES2530755T3 (es) | 2010-05-21 | 2015-03-05 | Glaxosmithkline Llc | Terapia de combinación para el tratamiento del cáncer |
NZ706745A (en) | 2010-06-04 | 2017-01-27 | Abraxis Bioscience Llc | Methods of treatment of pancreatic cancer |
JP2013538042A (ja) | 2010-06-16 | 2013-10-10 | ユニバーシティ オブ ピッツバーグ − オブ ザ コモンウェルス システム オブ ハイヤー エデュケイション | エンドプラスミンに対する抗体およびその使用 |
WO2011161217A2 (en) | 2010-06-23 | 2011-12-29 | Palacký University in Olomouc | Targeting of vegfr2 |
BR112012032462A2 (pt) | 2010-06-25 | 2016-11-08 | Eisai R&D Man Co Ltd | agente antitumoral empregando compostos que, em combinação, têm efeito inibidor de quinase. |
WO2012006503A1 (en) | 2010-07-09 | 2012-01-12 | Genentech, Inc. | Anti-neuropilin antibodies and methods of use |
CN102344445B (zh) * | 2010-07-23 | 2015-11-25 | 岑均达 | 光学纯喹唑啉类化合物 |
CN102344444B (zh) * | 2010-07-23 | 2015-07-01 | 岑均达 | 光学纯喹唑啉类化合物 |
AR082418A1 (es) | 2010-08-02 | 2012-12-05 | Novartis Ag | Formas cristalinas de 1-(4-metil-5-[2-(2,2,2-trifluoro-1,1-dimetil-etil)-piridin-4-il]-tiazol-2-il)-amida de 2-amida del acido (s)-pirrolidin-1,2-dicarboxilico |
DK2612151T3 (en) | 2010-08-31 | 2017-10-02 | Genentech Inc | BIOMARKETS AND METHODS OF TREATMENT |
ES2543151T3 (es) | 2010-10-20 | 2015-08-17 | Pfizer Inc | Derivados de 2-piridina como moduladores del receptor Smoothened |
WO2012052745A1 (en) | 2010-10-21 | 2012-04-26 | Centro Nacional De Investigaciones Oncológicas (Cnio) | Combinations of pi3k inhibitors with a second anti -tumor agent |
US20130236467A1 (en) | 2010-11-24 | 2013-09-12 | Jeremy Griggs | Multispecific antigen binding proteins targeting hgf |
CN102558159A (zh) * | 2010-12-20 | 2012-07-11 | 天津药物研究院 | 4-取代间甲磺酰胺苯胺基-喹唑啉衍生物及其制备方法和用途 |
CN102558160B (zh) * | 2010-12-20 | 2015-09-23 | 天津药物研究院 | 4-取代对甲磺酰胺苯胺基-喹唑啉衍生物及其制备方法和用途 |
EP2468883A1 (en) | 2010-12-22 | 2012-06-27 | Pangaea Biotech S.L. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
US8952154B2 (en) | 2010-12-23 | 2015-02-10 | Apotex Pharmachem Inc. | Process for the preparation of lapatinib and its ditosylate salt |
US9134297B2 (en) | 2011-01-11 | 2015-09-15 | Icahn School Of Medicine At Mount Sinai | Method and compositions for treating cancer and related methods |
WO2012098387A1 (en) | 2011-01-18 | 2012-07-26 | Centro Nacional De Investigaciones Oncológicas (Cnio) | 6, 7-ring-fused triazolo [4, 3 - b] pyridazine derivatives as pim inhibitors |
PL2670753T3 (pl) | 2011-01-31 | 2017-05-31 | Novartis Ag | Nowe pochodne heterocykliczne |
US20120214830A1 (en) | 2011-02-22 | 2012-08-23 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma |
EP2492688A1 (en) | 2011-02-23 | 2012-08-29 | Pangaea Biotech, S.A. | Molecular biomarkers for predicting response to antitumor treatment in lung cancer |
KR102061743B1 (ko) | 2011-03-04 | 2020-01-03 | 뉴젠 세러퓨틱스 인코포레이티드 | 알킨 치환된 퀴나졸린 화합물 및 그것의 사용 방법 |
CA2829131C (en) | 2011-03-04 | 2018-11-20 | Glaxosmithkline Intellectual Property (No.2) Limited | Amino-quinolines as kinase inhibitors |
MX2013010330A (es) | 2011-03-09 | 2014-11-26 | Richard G Pestell | Líneas de célula cancerosa de próstata, signaturas de gen, y usos de las mismas. |
CN103648500B (zh) | 2011-03-17 | 2016-05-04 | 宾夕法尼亚大学理事会 | 双功能酶制钳型分子的方法和用途 |
US9295676B2 (en) | 2011-03-17 | 2016-03-29 | The Trustees Of The University Of Pennsylvania | Mutation mimicking compounds that bind to the kinase domain of EGFR |
WO2012129145A1 (en) | 2011-03-18 | 2012-09-27 | OSI Pharmaceuticals, LLC | Nscle combination therapy |
WO2012129344A1 (en) | 2011-03-23 | 2012-09-27 | Amgen Inc. | Fused tricyclic dual inhibitors of cdk 4/6 and flt3 |
ES2620644T3 (es) | 2011-04-01 | 2017-06-29 | Genentech, Inc. | Combinaciones de compuestos inhibidores de AKT y agentes quimioterapéuticos, y métodos de uso |
WO2012142164A1 (en) | 2011-04-12 | 2012-10-18 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Human monoclonal antibodies that bind insulin-like growth factor (igf) i and ii |
US8962650B2 (en) | 2011-04-18 | 2015-02-24 | Eisai R&D Management Co., Ltd. | Therapeutic agent for tumor |
US20140178368A1 (en) | 2011-04-19 | 2014-06-26 | Leslie Lynne SHARP | Combinations of anti-4-1bb antibodies and adcc-inducing antibodies for the treatment of cancer |
US9896730B2 (en) | 2011-04-25 | 2018-02-20 | OSI Pharmaceuticals, LLC | Use of EMT gene signatures in cancer drug discovery, diagnostics, and treatment |
WO2012155339A1 (zh) * | 2011-05-17 | 2012-11-22 | 江苏康缘药业股份有限公司 | 4-苯胺-6-丁烯酰胺-7-烷醚喹唑啉衍生物及其制备方法和用途 |
EP2524918A1 (en) | 2011-05-19 | 2012-11-21 | Centro Nacional de Investigaciones Oncológicas (CNIO) | Imidazopyrazines derivates as kinase inhibitors |
KR101953210B1 (ko) | 2011-05-19 | 2019-02-28 | 푼다시온 센트로 나시오날 드 인베스티가시오네스 온콜로기카스 카를로스Ⅲ | 단백질 키나아제 억제제로서의 대환식 화합물 |
ITMI20110894A1 (it) * | 2011-05-20 | 2012-11-21 | Italiana Sint Spa | Impurezza del lapatinib e suoi sali |
JP5414739B2 (ja) | 2011-05-25 | 2014-02-12 | 三菱電機株式会社 | 半導体テスト治具 |
EP3444363B1 (en) | 2011-06-03 | 2020-11-25 | Eisai R&D Management Co., Ltd. | Biomarkers for prediciting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds |
WO2013005057A1 (en) | 2011-07-07 | 2013-01-10 | Centro Nacional De Investigaciones Oncológicas (Cnio) | New compounds |
WO2013004984A1 (en) | 2011-07-07 | 2013-01-10 | Centro Nacional De Investigaciones Oncologicas (Cnio) | Tricyclic compounds for use as kinase inhibitors |
WO2013005041A1 (en) | 2011-07-07 | 2013-01-10 | Centro Nacional De Investigaciones Oncológicas (Cnio) | Tricyclic heterocyclic compounds as kinase inhibitors |
EP3409278B8 (en) | 2011-07-21 | 2020-11-04 | Sumitomo Dainippon Pharma Oncology, Inc. | Heterocyclic protein kinase inhibitors |
WO2013025939A2 (en) | 2011-08-16 | 2013-02-21 | Indiana University Research And Technology Corporation | Compounds and methods for treating cancer by inhibiting the urokinase receptor |
TWI547494B (zh) | 2011-08-18 | 2016-09-01 | 葛蘭素史克智慧財產發展有限公司 | 作為激酶抑制劑之胺基喹唑啉類 |
BR112014004762A2 (pt) | 2011-08-31 | 2018-06-19 | Genentech Inc | métodos de determinação da sensibilidade de crescimento de célula tumoral á inibição por um inibidor de quinase de egfr, de identificação de um paciente com câncer que provavelmente irá se beneficiar do tratamento com um inibidor de efgr, de tratamento de um câncer em um paciente, de seleção de uma terapia para um paciente com câncer e de determinação de superexpressão de gene erbb2 em uma célula |
CA2847540C (en) | 2011-09-22 | 2016-05-17 | Pfizer Inc. | Pyrrolopyrimidine and purine derivatives |
MX2014003698A (es) | 2011-09-30 | 2014-07-28 | Genentech Inc | Marcadores de diagnostico. |
WO2013050725A1 (en) | 2011-10-04 | 2013-04-11 | King's College London | Ige anti -hmw-maa antibody |
MX340452B (es) | 2011-10-28 | 2016-07-08 | Novartis Ag | Novedosos derivados de purina y su uso en el tratamiento de enfermedades. |
CA2856149A1 (en) | 2011-11-08 | 2013-05-16 | Pfizer Inc. | Methods of treating inflammatory disorders using anti-m-csf antibodies |
WO2013080218A1 (en) | 2011-11-28 | 2013-06-06 | Fresenius Kabi Oncology Ltd. | Novel intermediates and process for the preparation of lapatinib and its pharmaceutically acceptable salts |
BR112014019034A8 (pt) | 2012-01-31 | 2017-07-11 | Smithkline Beecham Cork Ltd | Método para tratamento de câncer |
AR090263A1 (es) | 2012-03-08 | 2014-10-29 | Hoffmann La Roche | Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma |
ES2894830T3 (es) | 2012-04-03 | 2022-02-16 | Novartis Ag | Productos combinados con inhibidores de tirosina·cinasa y su uso |
WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
JP6518585B2 (ja) | 2012-05-14 | 2019-05-22 | リチャード ジー. ペステル | がんの治療のためのccr5の修飾薬の使用 |
WO2013173283A1 (en) | 2012-05-16 | 2013-11-21 | Novartis Ag | Dosage regimen for a pi-3 kinase inhibitor |
WO2013190089A1 (en) | 2012-06-21 | 2013-12-27 | Pangaea Biotech, S.L. | Molecular biomarkers for predicting outcome in lung cancer |
US9505749B2 (en) | 2012-08-29 | 2016-11-29 | Amgen Inc. | Quinazolinone compounds and derivatives thereof |
TWI592417B (zh) | 2012-09-13 | 2017-07-21 | 葛蘭素史克智慧財產發展有限公司 | 胺基喹唑啉激酶抑制劑之前藥 |
ES2644758T3 (es) | 2012-10-16 | 2017-11-30 | Tolero Pharmaceuticals, Inc. | Moduladores de PKM2 y métodos para su uso |
CZ2012712A3 (cs) | 2012-10-17 | 2014-04-30 | Zentiva, K.S. | Nový způsob výroby klíčového intermediátu výroby lapatinibu |
CN102942561A (zh) * | 2012-11-06 | 2013-02-27 | 深圳海王药业有限公司 | 4-氨基喹唑啉杂环化合物及其用途 |
US9260426B2 (en) | 2012-12-14 | 2016-02-16 | Arrien Pharmaceuticals Llc | Substituted 1H-pyrrolo [2, 3-b] pyridine and 1H-pyrazolo [3, 4-b] pyridine derivatives as salt inducible kinase 2 (SIK2) inhibitors |
MX2015004979A (es) | 2012-12-21 | 2015-07-17 | Eisai R&D Man Co Ltd | Forma amorfa de derivado de quinolina y metodo para su produccion. |
CN103896889B (zh) * | 2012-12-27 | 2016-05-25 | 上海创诺制药有限公司 | 拉帕替尼中间体及其制备方法和应用 |
WO2014127214A1 (en) | 2013-02-15 | 2014-08-21 | Kala Pharmaceuticals, Inc. | Therapeutic compounds and uses thereof |
ES2635620T3 (es) | 2013-02-19 | 2017-10-04 | Hexal Ag | Composición farmacéutica que comprende n-[3-cloro-4-(3-fluorobenciloxi)fenil]-6-[5({[2-(metilsulfonil)etil]amino} metil)-2-furil]quinazolin-4-amina o una sal, solvato o sal solvatada farmacéuticamente aceptables de la misma |
US9688688B2 (en) | 2013-02-20 | 2017-06-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof |
JP2016510000A (ja) | 2013-02-20 | 2016-04-04 | カラ ファーマシューティカルズ インコーポレイテッド | 治療用化合物およびその使用 |
CA2902132C (en) | 2013-02-21 | 2020-09-22 | Glaxosmithkline Intellectual Property Development Limited | Quinazolines as kinase inhibitors |
KR20150118159A (ko) | 2013-02-22 | 2015-10-21 | 에프. 호프만-라 로슈 아게 | 암의 치료 방법 및 약물 내성의 예방 방법 |
CN103159747A (zh) * | 2013-02-26 | 2013-06-19 | 常州鸿创高分子科技有限公司 | 一种二对甲苯磺酸拉帕替尼的合成方法 |
AU2014223548A1 (en) | 2013-02-26 | 2015-10-15 | Triact Therapeutics, Inc. | Cancer therapy |
US9468681B2 (en) | 2013-03-01 | 2016-10-18 | California Institute Of Technology | Targeted nanoparticles |
KR20150123250A (ko) | 2013-03-06 | 2015-11-03 | 제넨테크, 인크. | 암 약물 내성의 치료 및 예방 방법 |
WO2014153030A2 (en) | 2013-03-14 | 2014-09-25 | Genentech, Inc. | Methods of treating cancer and preventing cancer drug resistance |
CN105308033B (zh) | 2013-03-14 | 2018-08-24 | 特雷罗药物股份有限公司 | Jak2和alk2抑制剂及其使用方法 |
CN105339001A (zh) | 2013-03-15 | 2016-02-17 | 基因泰克公司 | 治疗癌症和预防癌症耐药性的方法 |
WO2014147246A1 (en) | 2013-03-21 | 2014-09-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Method and pharmaceutical composition for use in the treatment of chronic liver diseases associated with a low hepcidin expression |
WO2014170910A1 (en) | 2013-04-04 | 2014-10-23 | Natco Pharma Limited | Process for the preparation of lapatinib |
US9206188B2 (en) | 2013-04-18 | 2015-12-08 | Arrien Pharmaceuticals Llc | Substituted pyrrolo[2,3-b]pyridines as ITK and JAK inhibitors |
ES2687968T3 (es) | 2013-05-14 | 2018-10-30 | Eisai R&D Management Co., Ltd. | Biomarcadores para pronosticar y evaluar la reactividad de sujetos con cáncer de endometrio a compuestos con lenvatinib |
HU231012B1 (hu) | 2013-05-24 | 2019-11-28 | Egis Gyógyszergyár Nyilvánosan Működő Részvénytársaság | Lapatinib sók |
CN105705494B (zh) * | 2013-07-18 | 2017-12-15 | 锦州奥鸿药业有限责任公司 | 喹唑啉衍生物及其药物组合物,以及作为药物的用途 |
WO2015035410A1 (en) | 2013-09-09 | 2015-03-12 | Triact Therapeutic, Inc. | Cancer therapy |
US9567643B2 (en) | 2013-10-04 | 2017-02-14 | Aptose Biosciences Inc. | Compositions and methods for treating cancers |
US9890173B2 (en) | 2013-11-01 | 2018-02-13 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
CA2928658A1 (en) | 2013-11-01 | 2015-05-07 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
CN103554091B (zh) * | 2013-11-05 | 2016-05-18 | 沈阳工业大学 | 喹唑啉衍生物及其制备方法和用途 |
UA115388C2 (uk) | 2013-11-21 | 2017-10-25 | Пфайзер Інк. | 2,6-заміщені пуринові похідні та їх застосування в лікуванні проліферативних захворювань |
CA2930359C (en) | 2013-12-06 | 2022-03-01 | Novartis Ag | Dosage regimen for an alpha-isoform selective phosphatidylinositol 3-kinase inhibitor |
US9242965B2 (en) | 2013-12-31 | 2016-01-26 | Boehringer Ingelheim International Gmbh | Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors |
UA121206C2 (uk) | 2014-01-24 | 2020-04-27 | Турнінґ Поінт Терапьютикс, Інк. | Діарильні макроцикли як модулятори протеїнкіназ |
WO2015128837A1 (en) | 2014-02-26 | 2015-09-03 | Glaxosmithkline Intellectual Property (No.2) Limited | Methods of treating cancer patients responding to ezh2 inhibitor gsk126 |
WO2015148531A1 (en) | 2014-03-24 | 2015-10-01 | Genentech, Inc. | Cancer treatment with c-met antagonists and correlation of the latter with hgf expression |
WO2015155624A1 (en) | 2014-04-10 | 2015-10-15 | Pfizer Inc. | Dihydropyrrolopyrimidine derivatives |
WO2015156674A2 (en) | 2014-04-10 | 2015-10-15 | Stichting Het Nederlands Kanker Instituut | Method for treating cancer |
EP2937346A1 (en) | 2014-04-24 | 2015-10-28 | F.I.S.- Fabbrica Italiana Sintetici S.p.A. | Co-crystals of lapatinib |
JP6574203B2 (ja) | 2014-04-30 | 2019-09-11 | ファイザー・インク | シクロアルキル結合ジヘテロ環誘導体 |
US9388239B2 (en) | 2014-05-01 | 2016-07-12 | Consejo Nacional De Investigation Cientifica | Anti-human VEGF antibodies with unusually strong binding affinity to human VEGF-A and cross reactivity to human VEGF-B |
WO2016001789A1 (en) | 2014-06-30 | 2016-01-07 | Pfizer Inc. | Pyrimidine derivatives as pi3k inhibitors for use in the treatment of cancer |
US10934360B2 (en) | 2014-07-31 | 2021-03-02 | The Hong Kong University Of Science And Technology | Human monoclonal antibodies against EPHA4 and their use |
BR112017002827B1 (pt) | 2014-08-28 | 2023-04-18 | Eisai R&D Management Co., Ltd | Derivado de quinolina altamente puro e método para produção do mesmo |
EP3206717B1 (en) | 2014-10-17 | 2020-11-25 | Novartis AG | Combination of ceritinib with an egfr inhibitor |
KR102139496B1 (ko) * | 2014-12-15 | 2020-07-30 | 더 리젠츠 오브 더 유니버시티 오브 미시간 | Egfr 및 pi3k의 소분자 억제제 |
WO2016097918A1 (en) | 2014-12-18 | 2016-06-23 | Pfizer Inc. | Pyrimidine and triazine derivatives and their use as axl inhibitors |
JP6900314B2 (ja) | 2014-12-24 | 2021-07-07 | ジェネンテック, インコーポレイテッド | 膀胱癌の治療、診断、及び予後判定方法 |
AU2016205311B2 (en) | 2015-01-08 | 2022-02-17 | The Board Of Trustees Of The Leland Stanford Junior University | Factors and cells that provide for induction of bone, bone marrow, and cartilage |
MA41414A (fr) | 2015-01-28 | 2017-12-05 | Centre Nat Rech Scient | Protéines de liaison agonistes d' icos |
US20180050993A1 (en) * | 2015-02-03 | 2018-02-22 | Trillium Therapeutics Inc. | Novel fluorinated derivatives as egfr inhibitors useful for treating cancers |
MX2017010474A (es) | 2015-02-25 | 2017-11-28 | Eisai R&D Man Co Ltd | Metodo para suprimir el amargor de un derivado de quinoleina. |
KR20240064733A (ko) | 2015-03-04 | 2024-05-13 | 머크 샤프 앤드 돔 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합 |
MX2017013383A (es) | 2015-04-20 | 2017-12-07 | Tolero Pharmaceuticals Inc | Prediccion de respuesta a alvocidib mediante perfilado mitocondrial. |
US10011629B2 (en) | 2015-05-01 | 2018-07-03 | Cocrystal Pharma, Inc. | Nucleoside analogs for treatment of the flaviviridae family of viruses and cancer |
TR201911032T4 (tr) | 2015-05-18 | 2019-08-21 | Tolero Pharmaceuticals Inc | Artırılmış biyoyararlanıma sahip alvocıdıb ön ilaçları. |
CN106279307B (zh) * | 2015-05-19 | 2019-07-26 | 正大天晴药业集团股份有限公司 | 芳氨代葡萄糖衍生物、其制备方法及抗肿瘤用途 |
SG11201710198YA (en) | 2015-06-16 | 2018-01-30 | Eisai R&D Man Co Ltd | Anticancer agent |
CN111643479B (zh) | 2015-07-01 | 2023-10-27 | 加州理工学院 | 基于阳离子粘酸聚合物的递送系统 |
CN107735399B (zh) | 2015-07-02 | 2021-01-26 | 特普医药公司 | 作为蛋白质激酶的调节剂的手性二芳基大环 |
WO2017009751A1 (en) | 2015-07-15 | 2017-01-19 | Pfizer Inc. | Pyrimidine derivatives |
KR20180033194A (ko) | 2015-07-21 | 2018-04-02 | 티피 테라퓨틱스, 인크. | 키랄 디아릴 매크로사이클 및 이것의 용도 |
AU2016301315C1 (en) | 2015-08-03 | 2022-07-07 | Sumitomo Pharma Oncology, Inc. | Combination therapies for treatment of cancer |
WO2017025871A1 (en) | 2015-08-07 | 2017-02-16 | Glaxosmithkline Intellectual Property Development Limited | Combination therapy comprising anti ctla-4 antibodies |
EP3350181B1 (en) * | 2015-09-02 | 2023-11-01 | The Regents of The University of California | Her3 ligands and uses thereof |
WO2017077445A1 (en) | 2015-11-02 | 2017-05-11 | Novartis Ag | Dosage regimen for a phosphatidylinositol 3-kinase inhibitor |
KR20180083936A (ko) | 2015-12-01 | 2018-07-23 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | 조합 치료 및 그의 용도 및 방법 |
EP3383375A1 (en) | 2015-12-03 | 2018-10-10 | Agios Pharmaceuticals, Inc. | Mat2a inhibitors for treating mtap null cancer |
CN109195593A (zh) | 2016-03-15 | 2019-01-11 | 奥莱松基因组股份有限公司 | 用于治疗实体瘤的lsd1抑制剂的组合 |
KR20190034225A (ko) | 2016-07-28 | 2019-04-01 | 티피 테라퓨틱스, 인크. | 거대환 키나제 억제제 |
EP3494140A1 (en) | 2016-08-04 | 2019-06-12 | GlaxoSmithKline Intellectual Property Development Ltd | Anti-icos and anti-pd-1 antibody combination therapy |
AU2017324251A1 (en) | 2016-09-08 | 2019-03-21 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
US10253036B2 (en) | 2016-09-08 | 2019-04-09 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
US10392399B2 (en) | 2016-09-08 | 2019-08-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
WO2018060833A1 (en) | 2016-09-27 | 2018-04-05 | Novartis Ag | Dosage regimen for alpha-isoform selective phosphatidylinositol 3-kinase inhibitor alpelisib |
WO2018094275A1 (en) | 2016-11-18 | 2018-05-24 | Tolero Pharmaceuticals, Inc. | Alvocidib prodrugs and their use as protein kinase inhibitors |
KR20190099260A (ko) | 2016-12-19 | 2019-08-26 | 톨레로 파마수티컬스, 인크. | 프로파일링 펩티드 및 감도 프로파일링을 위한 방법 |
RS62456B1 (sr) | 2016-12-22 | 2021-11-30 | Amgen Inc | Derivati benzizotiazola, izotiazolo[3,4-b]piridina, hinazolina, ftalazina, pirido[2,3-d]piridazina i pirido[2,3-d]pirimidina kao kras g12c inhibitori za tretman raka pluća, pankreasa ili debelog creva |
TWI808958B (zh) | 2017-01-25 | 2023-07-21 | 美商特普醫葯公司 | 涉及二芳基巨環化合物之組合療法 |
JOP20190272A1 (ar) | 2017-05-22 | 2019-11-21 | Amgen Inc | مثبطات kras g12c وطرق لاستخدامها |
MY201925A (en) | 2017-07-28 | 2024-03-23 | Turning Point Therapeutics Inc | Macrocyclic compounds and uses thereof |
CA3075046A1 (en) | 2017-09-08 | 2019-03-14 | Amgen Inc. | Inhibitors of kras g12c and methods of using the same |
WO2019055579A1 (en) | 2017-09-12 | 2019-03-21 | Tolero Pharmaceuticals, Inc. | TREATMENT REGIME FOR CANCERS THAT ARE INSENSITIVE TO BCL-2 INHIBITORS USING THE MCL-1 ALVOCIDIB INHIBITOR |
WO2019075367A1 (en) | 2017-10-13 | 2019-04-18 | Tolero Pharmaceuticals, Inc. | PKM2 ACTIVATORS IN COMBINATION WITH OXYGEN REACTIVE SPECIES FOR THE TREATMENT OF CANCER |
US11708335B2 (en) | 2017-12-18 | 2023-07-25 | Sterngreene, Inc. | Pyrimidine compounds useful as tyrosine kinase inhibitors |
HRP20221502T1 (hr) | 2017-12-19 | 2023-03-31 | Turning Point Therapeutics, Inc. | Makrociklički spojevi za liječenje bolesti |
MA52501A (fr) | 2018-05-04 | 2021-03-10 | Amgen Inc | Inhibiteurs de kras g12c et leurs procédés d'utilisation |
MA52496A (fr) | 2018-05-04 | 2021-03-10 | Amgen Inc | Inhibiteurs de kras g12c et leurs procédés d'utilisation |
WO2019217691A1 (en) | 2018-05-10 | 2019-11-14 | Amgen Inc. | Kras g12c inhibitors for the treatment of cancer |
JP7360396B2 (ja) | 2018-06-01 | 2023-10-12 | アムジエン・インコーポレーテツド | Kras g12c阻害剤及び同一物の使用方法 |
JP7357644B2 (ja) | 2018-06-11 | 2023-10-06 | アムジエン・インコーポレーテツド | がんを処置するためのkras g12c阻害剤 |
WO2020050890A2 (en) | 2018-06-12 | 2020-03-12 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
WO2019241327A1 (en) | 2018-06-13 | 2019-12-19 | California Institute Of Technology | Nanoparticles for crossing the blood brain barrier and methods of treatment using the same |
SG11202013029UA (en) * | 2018-06-27 | 2021-01-28 | Oscotec Inc | Pyridopyrimidinone derivatives for use as axl inhibitors |
CN112512597A (zh) | 2018-07-26 | 2021-03-16 | 大日本住友制药肿瘤公司 | 用于治疗与acvr1表达异常相关的疾病的方法以及用于此的acvr1抑制剂 |
EP3860608A1 (en) | 2018-10-04 | 2021-08-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Egfr inhibitors for treating keratodermas |
JP7516029B2 (ja) | 2018-11-16 | 2024-07-16 | アムジエン・インコーポレーテツド | Kras g12c阻害剤化合物の重要な中間体の改良合成法 |
WO2020106640A1 (en) | 2018-11-19 | 2020-05-28 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
JP7377679B2 (ja) | 2018-11-19 | 2023-11-10 | アムジエン・インコーポレーテツド | がん治療のためのkrasg12c阻害剤及び1種以上の薬学的に活性な追加の薬剤を含む併用療法 |
WO2020117988A1 (en) | 2018-12-04 | 2020-06-11 | Tolero Pharmaceuticals, Inc. | Cdk9 inhibitors and polymorphs thereof for use as agents for treatment of cancer |
WO2020131674A1 (en) | 2018-12-19 | 2020-06-25 | Array Biopharma Inc. | 7-((3,5-dimethoxyphenyl)amino)quinoxaline derivatives as fgfr inhibitors for treating cancer |
US20220081438A1 (en) | 2018-12-19 | 2022-03-17 | Array Biopharma Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as inhibitors of fgfr tyrosine kinases |
CA3123042A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Kif18a inhibitors |
WO2020132649A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Heteroaryl amides useful as kif18a inhibitors |
EP3898592A1 (en) | 2018-12-20 | 2021-10-27 | Amgen Inc. | Heteroaryl amides useful as kif18a inhibitors |
TWI844602B (zh) | 2018-12-20 | 2024-06-11 | 美商安進公司 | Kif18a抑制劑 |
AU2020214412A1 (en) | 2019-02-01 | 2021-08-12 | Glaxosmithkline Intellectual Property Development Limited | Belantamab mafodotin in combination with pembrolizumab for treating cancer |
CA3127502A1 (en) | 2019-02-12 | 2020-08-20 | Sumitomo Dainippon Pharma Oncology, Inc. | Formulations comprising heterocyclic protein kinase inhibitors |
WO2020180768A1 (en) | 2019-03-01 | 2020-09-10 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
AU2020232616A1 (en) | 2019-03-01 | 2021-09-09 | Revolution Medicines, Inc. | Bicyclic heterocyclyl compounds and uses thereof |
US11793802B2 (en) | 2019-03-20 | 2023-10-24 | Sumitomo Pharma Oncology, Inc. | Treatment of acute myeloid leukemia (AML) with venetoclax failure |
EP3941463A1 (en) | 2019-03-22 | 2022-01-26 | Sumitomo Dainippon Pharma Oncology, Inc. | Compositions comprising pkm2 modulators and methods of treatment using the same |
EP3738593A1 (en) | 2019-05-14 | 2020-11-18 | Amgen, Inc | Dosing of kras inhibitor for treatment of cancers |
MX2021014126A (es) | 2019-05-21 | 2022-01-04 | Amgen Inc | Formas en estado solido. |
MA56397A (fr) | 2019-06-26 | 2022-05-04 | Glaxosmithkline Ip Dev Ltd | Protéines de liaison à l'il1rap |
MX2022001296A (es) | 2019-08-02 | 2022-02-22 | Amgen Inc | Inhibidores de kif18a. |
AU2020325115A1 (en) | 2019-08-02 | 2022-03-17 | Amgen Inc. | Pyridine derivatives as KIF18A inhibitors |
JP2022542394A (ja) | 2019-08-02 | 2022-10-03 | アムジエン・インコーポレーテツド | Kif18a阻害剤として有用なヘテロアリールアミド |
JP2022542967A (ja) | 2019-08-02 | 2022-10-07 | アムジエン・インコーポレーテツド | Kif18a阻害剤 |
WO2021046289A1 (en) | 2019-09-06 | 2021-03-11 | Glaxosmithkline Intellectual Property Development Limited | Dosing regimen for the treatment of cancer with an anti icos agonistic antibody and ipilimumab |
WO2021043961A1 (en) | 2019-09-06 | 2021-03-11 | Glaxosmithkline Intellectual Property Development Limited | Dosing regimen for the treatment of cancer with an anti icos agonistic antibody and chemotherapy |
MX2022004656A (es) | 2019-10-24 | 2022-05-25 | Amgen Inc | Derivados de piridopirimidina utiles como inhibidores de kras g12c y kras g12d en el tratamiento del cancer. |
CR20220240A (es) | 2019-11-04 | 2022-08-03 | Revolution Medicines Inc | Inhibidores de ras |
TW202132314A (zh) | 2019-11-04 | 2021-09-01 | 美商銳新醫藥公司 | Ras抑制劑 |
TW202132316A (zh) | 2019-11-04 | 2021-09-01 | 美商銳新醫藥公司 | Ras抑制劑 |
CN114901662A (zh) | 2019-11-08 | 2022-08-12 | 锐新医药公司 | 双环杂芳基化合物及其用途 |
BR112022009390A2 (pt) | 2019-11-14 | 2022-08-09 | Amgen Inc | Síntese melhorada de composto inibidor de kras g12c |
US20230192682A1 (en) | 2019-11-14 | 2023-06-22 | Amgen Inc. | Improved synthesis of kras g12c inhibitor compound |
WO2021108683A1 (en) | 2019-11-27 | 2021-06-03 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
IL294484A (en) | 2020-01-07 | 2022-09-01 | Revolution Medicines Inc | Dosage for shp2 inhibitor and methods for treating cancer |
BR112022014562A2 (pt) | 2020-01-28 | 2022-09-13 | Glaxosmithkline Ip Dev Ltd | Tratamentos de combinação, usos e métodos dos mesmos |
WO2021155006A1 (en) | 2020-01-31 | 2021-08-05 | Les Laboratoires Servier Sas | Inhibitors of cyclin-dependent kinases and uses thereof |
CA3174455A1 (en) * | 2020-03-02 | 2021-09-10 | Turning Point Therapeutics, Inc. | Therapeutic uses of macrocyclic compounds |
BR112022025550A2 (pt) | 2020-06-18 | 2023-03-07 | Revolution Medicines Inc | Métodos para retardar, prevenir e tratar resistência adquirida aos inibidores de ras |
CA3187757A1 (en) | 2020-09-03 | 2022-03-24 | Ethan AHLER | Use of sos1 inhibitors to treat malignancies with shp2 mutations |
TW202227460A (zh) | 2020-09-15 | 2022-07-16 | 美商銳新醫藥公司 | Ras抑制劑 |
JP2024501280A (ja) | 2020-12-22 | 2024-01-11 | キル・レガー・セラピューティクス・インコーポレーテッド | Sos1阻害剤およびその使用 |
MX2023007550A (es) | 2020-12-22 | 2023-11-14 | Mekanistic Therapeutics Llc | Compuestos de aminobencil heteroarilo sustituidos como inhibidores de receptor de factor de crecimiento epidermico (egfr) y/o fosfoinositol 3-cinasa (pi3k). |
WO2022221227A1 (en) | 2021-04-13 | 2022-10-20 | Nuvalent, Inc. | Amino-substituted heterocycles for treating cancers with egfr mutations |
JP2024516450A (ja) | 2021-05-05 | 2024-04-15 | レボリューション メディシンズ インコーポレイテッド | 共有結合性ras阻害剤及びその使用 |
CR20230570A (es) | 2021-05-05 | 2024-01-22 | Revolution Medicines Inc | Inhibidores de ras |
TW202309053A (zh) | 2021-05-05 | 2023-03-01 | 美商銳新醫藥公司 | Ras抑制劑 |
AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
WO2023114954A1 (en) | 2021-12-17 | 2023-06-22 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
WO2023172940A1 (en) | 2022-03-08 | 2023-09-14 | Revolution Medicines, Inc. | Methods for treating immune refractory lung cancer |
WO2023240263A1 (en) | 2022-06-10 | 2023-12-14 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
WO2024081916A1 (en) | 2022-10-14 | 2024-04-18 | Black Diamond Therapeutics, Inc. | Methods of treating cancers using isoquinoline or 6-aza-quinoline derivatives |
Family Cites Families (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4074057A (en) | 1973-12-12 | 1978-02-14 | Takeda Chemical Co., Ltd. | 2-Halopropionic acid and its derivatives |
US4166735A (en) | 1977-01-21 | 1979-09-04 | Shell Oil Company | Cycloalkanecarboxanilide derivative herbicides |
EP0222839A4 (en) | 1985-05-17 | 1988-11-09 | Univ Australian | ANTI-MALARIA COMPOUNDS. |
US5141941A (en) | 1988-11-21 | 1992-08-25 | Ube Industries, Ltd. | Aralkylamine derivatives, and fungicides containing the same |
US5034393A (en) | 1989-07-27 | 1991-07-23 | Dowelanco | Fungicidal use of pyridopyrimidine, pteridine, pyrimidopyrimidine, pyrimidopyridazine, and pyrimido-1,2,4-triazine derivatives |
CA2039411A1 (en) | 1990-03-30 | 1991-10-01 | Ronnie Gerald Edie | Thienopyrimidine derivatives |
US5480883A (en) | 1991-05-10 | 1996-01-02 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
US5710158A (en) | 1991-05-10 | 1998-01-20 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
DE4131924A1 (de) | 1991-09-25 | 1993-07-08 | Hoechst Ag | Substituierte 4-alkoxypyrimidine, verfahren zu ihrer herstellung und ihre verwendung als schaedlingsbekaempfungsmittel |
GB9127252D0 (en) | 1991-12-23 | 1992-02-19 | Boots Co Plc | Therapeutic agents |
AU661533B2 (en) | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
WO1993017682A1 (en) | 1992-03-04 | 1993-09-16 | Abbott Laboratories | Angiotensin ii receptor antagonists |
WO1993018035A1 (en) | 1992-03-04 | 1993-09-16 | Abbott Laboratories | Angiotensin ii receptor antagonists |
US5326766A (en) | 1992-08-19 | 1994-07-05 | Dreikorn Barry A | 4-(2-(4-(2-pyridinyloxy)phenyl)ethoxy)quinazoline and analogues thereof |
DE4308014A1 (de) | 1993-03-13 | 1994-09-15 | Hoechst Schering Agrevo Gmbh | Kondensierte Stickstoffheterocyclen, Verfahren zu ihrer Herstellung und ihre Verwendung als Schädlingsbekämpfungsmittel und Fungizide |
GB9312891D0 (en) | 1993-06-22 | 1993-08-04 | Boots Co Plc | Therapeutic agents |
US5654307A (en) | 1994-01-25 | 1997-08-05 | Warner-Lambert Company | Bicyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family |
IL112249A (en) * | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
WO1995024190A2 (en) | 1994-03-07 | 1995-09-14 | Sugen, Inc. | Receptor tyrosine kinase inhibitors for inhibiting cell proliferative disorders and compositions thereof |
GB9510757D0 (en) | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
TW321649B (zh) * | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
GB9424233D0 (en) | 1994-11-30 | 1995-01-18 | Zeneca Ltd | Quinazoline derivatives |
MX9709867A (es) | 1995-06-07 | 1998-03-31 | Pfizer | Derivados de pirimidina condensados con un anillo heterociclico, composiciones que contienen los mismos, y uso de los mismos. |
GB9514265D0 (en) | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
AR004010A1 (es) | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | Compuestos heterociclicos |
WO1997018212A1 (en) | 1995-11-14 | 1997-05-22 | Pharmacia & Upjohn S.P.A. | Aryl and heteroaryl purine compounds |
GB9603095D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
HRP970371A2 (en) * | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
PT912559E (pt) * | 1996-07-13 | 2003-03-31 | Glaxo Group Ltd | Compostos heterociclicos fundidos como inibidores de proteina tirosina quinase |
EP0912572B1 (en) | 1996-07-13 | 2003-01-15 | Glaxo Group Limited | Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors |
ID18494A (id) | 1996-10-02 | 1998-04-16 | Novartis Ag | Turunan pirazola leburan dan proses pembuatannya |
RS49779B (sr) * | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
MXPA02012870A (es) * | 2000-06-22 | 2003-05-14 | Pfizer Prod Inc | Derivados biciclicos sustituidos para el tratamiento del crecimiento celular anormal. |
BR0111947A (pt) * | 2000-06-30 | 2003-05-06 | Glaxo Group Ltd | Composto, composição farmacêutica, método para o tratamento de um distúrbio em um mamìfero, uso de um composto e processo para preparar, um composto |
JP4458746B2 (ja) * | 2001-01-16 | 2010-04-28 | グラクソ グループ リミテッド | 癌の治療方法 |
RU2362774C1 (ru) * | 2002-02-01 | 2009-07-27 | Астразенека Аб | Хиназолиновые соединения |
US7488823B2 (en) * | 2003-11-10 | 2009-02-10 | Array Biopharma, Inc. | Cyanoguanidines and cyanoamidines as ErbB2 and EGFR inhibitors |
-
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Cited By (6)
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WO2010083720A1 (zh) * | 2009-01-23 | 2010-07-29 | Cen Junda | 光学纯喹唑啉类化合物 |
US8916574B2 (en) | 2009-09-28 | 2014-12-23 | Qilu Pharmaceutical Co., Ltd. | 4-(substituted anilino)-quinazoline derivatives useful as tyrosine kinase inhibitors |
CN102911163B (zh) * | 2011-08-01 | 2016-05-11 | 杭州民生药业有限公司 | 喹唑啉衍生物、含该衍生物的组合物及所述衍生物的制药用途 |
CN105801565A (zh) * | 2014-12-30 | 2016-07-27 | 天津法莫西医药科技有限公司 | N-[3-氯-4-[(3-氟苯基)甲氧基]苯基]-6-[(5-甲酰基)呋喃-2-基]-4-喹唑啉胺制备方法 |
CN105801565B (zh) * | 2014-12-30 | 2020-04-03 | 天津法莫西医药科技有限公司 | N-[3-氯-4-[(3-氟苯基)甲氧基]苯基]-6-[(5-甲酰基)呋喃-2-基]-4-喹唑啉胺制备方法 |
CN106632276A (zh) * | 2015-10-28 | 2017-05-10 | 上海天慈生物谷生物工程有限公司 | 一种治疗乳腺癌药物的制备方法 |
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