JP4291413B2 - キナゾリン誘導体 - Google Patents
キナゾリン誘導体 Download PDFInfo
- Publication number
- JP4291413B2 JP4291413B2 JP52256897A JP52256897A JP4291413B2 JP 4291413 B2 JP4291413 B2 JP 4291413B2 JP 52256897 A JP52256897 A JP 52256897A JP 52256897 A JP52256897 A JP 52256897A JP 4291413 B2 JP4291413 B2 JP 4291413B2
- Authority
- JP
- Japan
- Prior art keywords
- methoxy
- quinazoline
- chloro
- mmol
- hydroxy
- 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 - Fee Related
Links
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title abstract description 7
- -1 cyano, amino Chemical group 0.000 claims abstract description 146
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 84
- 239000001257 hydrogen Substances 0.000 claims abstract description 84
- 150000003839 salts Chemical class 0.000 claims abstract description 72
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 61
- 125000005843 halogen group Chemical group 0.000 claims abstract description 29
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 28
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 24
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 11
- 125000006615 aromatic heterocyclic group Chemical class 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 562
- 150000002431 hydrogen Chemical class 0.000 claims description 53
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 22
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 17
- 150000003246 quinazolines Chemical class 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000004848 alkoxyethyl group Chemical group 0.000 claims description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 125000005518 carboxamido group Chemical group 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- HXFKORYWVZYGRC-UHFFFAOYSA-N n-(4-chloro-2-fluorophenyl)-6-methoxy-7-(2-pyridin-2-yloxyethoxy)quinazolin-4-amine Chemical compound N1=CN=C2C=C(OCCOC=3N=CC=CC=3)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F HXFKORYWVZYGRC-UHFFFAOYSA-N 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- VQUUMWJYJNQUDX-UHFFFAOYSA-N 2-chloro-4-fluoro-5-[(6-methoxy-7-phenylmethoxyquinazolin-4-yl)amino]phenol Chemical compound N1=CN=C2C=C(OCC=3C=CC=CC=3)C(OC)=CC2=C1NC1=CC(O)=C(Cl)C=C1F VQUUMWJYJNQUDX-UHFFFAOYSA-N 0.000 claims description 2
- CKYOIUOEFJABQM-UHFFFAOYSA-N 5-[[6-methoxy-7-(pyridin-2-ylmethoxy)quinazolin-4-yl]amino]-2-methylphenol;5-[[6-methoxy-7-(pyridin-4-ylmethoxy)quinazolin-4-yl]amino]-2-methylphenol Chemical compound N1=CN=C2C=C(OCC=3C=CN=CC=3)C(OC)=CC2=C1NC1=CC=C(C)C(O)=C1.N1=CN=C2C=C(OCC=3N=CC=CC=3)C(OC)=CC2=C1NC1=CC=C(C)C(O)=C1 CKYOIUOEFJABQM-UHFFFAOYSA-N 0.000 claims description 2
- PIUHOZHDXUZWSN-UHFFFAOYSA-N 5-[[6-methoxy-7-(pyridin-3-ylmethoxy)quinazolin-4-yl]amino]-2-methylphenol;5-[[6-methoxy-7-(thiophen-3-ylmethoxy)quinazolin-4-yl]amino]-2-methylphenol Chemical compound N1=CN=C2C=C(OCC3=CSC=C3)C(OC)=CC2=C1NC1=CC=C(C)C(O)=C1.N1=CN=C2C=C(OCC=3C=NC=CC=3)C(OC)=CC2=C1NC1=CC=C(C)C(O)=C1 PIUHOZHDXUZWSN-UHFFFAOYSA-N 0.000 claims description 2
- NQUVPDVZPPKBSE-UHFFFAOYSA-N ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCC2=CC(=NC=C2)C#N)C=C1)F.ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCCC=2N(C=CN2)C)C=C1)F Chemical compound ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCC2=CC(=NC=C2)C#N)C=C1)F.ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCCC=2N(C=CN2)C)C=C1)F NQUVPDVZPPKBSE-UHFFFAOYSA-N 0.000 claims description 2
- RBJNTUFSVQQNQR-UHFFFAOYSA-N ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCC2=CC=NC=C2)C=C1)F.ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCCC2=CC=NC=C2)C=C1)F Chemical compound ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCC2=CC=NC=C2)C=C1)F.ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCCC2=CC=NC=C2)C=C1)F RBJNTUFSVQQNQR-UHFFFAOYSA-N 0.000 claims description 2
- JAUULSWVLCBTNE-UHFFFAOYSA-N ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCCN2C=CC(C=C2)=O)C=C1)F.ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCCOC2=CC=NC=C2)C=C1)F Chemical compound ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCCN2C=CC(C=C2)=O)C=C1)F.ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCCOC2=CC=NC=C2)C=C1)F JAUULSWVLCBTNE-UHFFFAOYSA-N 0.000 claims description 2
- BKNFGYUINMCGJZ-UHFFFAOYSA-N ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCCNC2=CC=NC=C2)C=C1)F.ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCCN2N=CN=C2)C=C1)F Chemical compound ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCCNC2=CC=NC=C2)C=C1)F.ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCCN2N=CN=C2)C=C1)F BKNFGYUINMCGJZ-UHFFFAOYSA-N 0.000 claims description 2
- WDRLWLKGEQSELD-UHFFFAOYSA-N N-(4-chloro-2-fluorophenyl)-6-methoxy-7-[2-(2-methylimidazol-1-yl)ethoxy]quinazolin-4-amine N-(4-chloro-2-fluorophenyl)-6-methoxy-7-[2-(1-methylimidazol-2-yl)sulfanylethoxy]quinazolin-4-amine Chemical compound ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCCSC=2N(C=CN2)C)C=C1)F.ClC1=CC(=C(NC2=NC=NC3=CC(=C(C=C23)OC)OCCN2C(=NC=C2)C)C=C1)F WDRLWLKGEQSELD-UHFFFAOYSA-N 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- AZROWFRYJGNGJB-UHFFFAOYSA-N 2-chloro-4-fluoro-5-[[6-methoxy-7-(2-pyridin-4-ylethoxy)quinazolin-4-yl]amino]phenol Chemical compound N1=CN=C2C=C(OCCC=3C=CN=CC=3)C(OC)=CC2=C1NC1=CC(O)=C(Cl)C=C1F AZROWFRYJGNGJB-UHFFFAOYSA-N 0.000 claims 1
- FOJARYAZSBLSFZ-UHFFFAOYSA-N 4-fluoro-5-[[6-methoxy-7-(thiophen-3-ylmethoxy)quinazolin-4-yl]amino]-2-methylphenol Chemical compound N1=CN=C2C=C(OCC3=CSC=C3)C(OC)=CC2=C1NC1=CC(O)=C(C)C=C1F FOJARYAZSBLSFZ-UHFFFAOYSA-N 0.000 claims 1
- 125000004103 aminoalkyl group Chemical group 0.000 claims 1
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- GIZAUGHNXZCPQV-UHFFFAOYSA-N n-(4-chloro-2-fluorophenyl)-7-[2-(2,4-dimethylimidazol-1-yl)ethoxy]-6-methoxyquinazolin-4-amine Chemical compound N1=CN=C2C=C(OCCN3C(=NC(C)=C3)C)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F GIZAUGHNXZCPQV-UHFFFAOYSA-N 0.000 claims 1
- HFSJQSNZGGBYPV-UHFFFAOYSA-N n-[4-[[4-(3-hydroxy-4-methylanilino)-6-methoxyquinazolin-7-yl]oxymethyl]-1,3-thiazol-2-yl]acetamide Chemical compound N1=CN=C2C=C(OCC=3N=C(NC(C)=O)SC=3)C(OC)=CC2=C1NC1=CC=C(C)C(O)=C1 HFSJQSNZGGBYPV-UHFFFAOYSA-N 0.000 claims 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 155
- 238000000034 method Methods 0.000 abstract description 68
- 230000008569 process Effects 0.000 abstract description 30
- 230000000694 effects Effects 0.000 abstract description 25
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 abstract description 17
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 abstract description 17
- 238000011282 treatment Methods 0.000 abstract description 14
- 206010028980 Neoplasm Diseases 0.000 abstract description 10
- 201000011510 cancer Diseases 0.000 abstract description 6
- 201000010099 disease Diseases 0.000 abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical class O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 abstract description 5
- 238000002360 preparation method Methods 0.000 abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 4
- 239000004480 active ingredient Substances 0.000 abstract description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 abstract 1
- 125000004414 alkyl thio group Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 490
- 239000000203 mixture Substances 0.000 description 334
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 328
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 300
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 207
- 229910001868 water Inorganic materials 0.000 description 195
- 238000001704 evaporation Methods 0.000 description 183
- 230000008020 evaporation Effects 0.000 description 183
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 182
- 238000001914 filtration Methods 0.000 description 169
- 239000000243 solution Substances 0.000 description 164
- 239000007787 solid Substances 0.000 description 159
- 239000007858 starting material Substances 0.000 description 151
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 139
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 135
- 239000002904 solvent Substances 0.000 description 132
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 126
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 111
- 238000000921 elemental analysis Methods 0.000 description 96
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 84
- 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 74
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 72
- 238000004440 column chromatography Methods 0.000 description 69
- 239000003039 volatile agent Substances 0.000 description 66
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 65
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 58
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 46
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 46
- XGZKSSTZBKFZMF-UHFFFAOYSA-N 4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolin-7-ol Chemical compound N1=CN=C2C=C(O)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F XGZKSSTZBKFZMF-UHFFFAOYSA-N 0.000 description 44
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 42
- 239000012267 brine Substances 0.000 description 41
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 41
- 239000002244 precipitate Substances 0.000 description 40
- 239000000284 extract Substances 0.000 description 38
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 37
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 37
- 238000010992 reflux Methods 0.000 description 37
- 229910000027 potassium carbonate Inorganic materials 0.000 description 36
- 239000012044 organic layer Substances 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 34
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
- 239000011541 reaction mixture Substances 0.000 description 31
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- 239000000725 suspension Substances 0.000 description 29
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 238000002844 melting Methods 0.000 description 26
- 230000008018 melting Effects 0.000 description 26
- 239000000706 filtrate Substances 0.000 description 24
- 235000019441 ethanol Nutrition 0.000 description 23
- 239000000047 product Substances 0.000 description 23
- 239000003054 catalyst Substances 0.000 description 22
- 239000012265 solid product Substances 0.000 description 22
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 19
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
- 238000005259 measurement Methods 0.000 description 19
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 17
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 16
- 229960001701 chloroform Drugs 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 16
- 239000012264 purified product Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- SGAUMIBSVBCMOS-UHFFFAOYSA-N [4-fluoro-5-[(7-hydroxy-6-methoxyquinazolin-4-yl)amino]-2-methylphenyl] methyl carbonate hydrochloride Chemical compound Cl.C1=C(C)C(OC(=O)OC)=CC(NC=2C3=CC(OC)=C(O)C=C3N=CN=2)=C1F SGAUMIBSVBCMOS-UHFFFAOYSA-N 0.000 description 13
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- AAMGKISRVPBVKF-UHFFFAOYSA-N [5-[(7-hydroxy-6-methoxyquinazolin-4-yl)amino]-2-methylphenyl] acetate hydrochloride Chemical compound Cl.N1=CN=C2C=C(O)C(OC)=CC2=C1NC1=CC=C(C)C(OC(C)=O)=C1 AAMGKISRVPBVKF-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 239000012312 sodium hydride Substances 0.000 description 12
- 229910000104 sodium hydride Inorganic materials 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 12
- 230000008728 vascular permeability Effects 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 239000003701 inert diluent Substances 0.000 description 11
- 239000012442 inert solvent Substances 0.000 description 11
- 239000002198 insoluble material Substances 0.000 description 11
- NSNFLSUFJFOYIJ-UHFFFAOYSA-N 4-chloro-6-methoxy-7-phenylmethoxyquinazoline;hydrochloride Chemical compound Cl.COC1=CC2=C(Cl)N=CN=C2C=C1OCC1=CC=CC=C1 NSNFLSUFJFOYIJ-UHFFFAOYSA-N 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 239000002480 mineral oil Substances 0.000 description 10
- 235000010446 mineral oil Nutrition 0.000 description 10
- VBUBADWLHFZFDK-UHFFFAOYSA-N quinazoline;hydrochloride Chemical compound Cl.N1=CN=CC2=CC=CC=C21 VBUBADWLHFZFDK-UHFFFAOYSA-N 0.000 description 10
- 239000000377 silicon dioxide Substances 0.000 description 10
- 238000001816 cooling Methods 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- OQJBFFCUFALWQL-UHFFFAOYSA-N n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)N=NC(=O)N1CCCCC1 OQJBFFCUFALWQL-UHFFFAOYSA-N 0.000 description 9
- 239000003208 petroleum Substances 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 239000005909 Kieselgur Substances 0.000 description 8
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 8
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- C07—ORGANIC CHEMISTRY
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- 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
- C07D239/88—Oxygen atoms
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- C07D239/72—Quinazolines; Hydrogenated quinazolines
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- 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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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
- C07D405/12—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 linked by a chain containing hetero atoms as chain links
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- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D417/00—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
- C07D417/02—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
- C07D417/12—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 linked by a chain containing hetero atoms as chain links
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP95402846 | 1995-12-18 | ||
| EP96402190 | 1996-10-15 | ||
| EP95402846.0 | 1996-10-15 | ||
| EP96402190.1 | 1996-10-15 | ||
| PCT/GB1996/003075 WO1997022596A1 (en) | 1995-12-18 | 1996-12-13 | Quinazoline derivatives |
Related Child Applications (1)
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| JP2008183259A Division JP2009007364A (ja) | 1996-10-15 | 2008-07-14 | キナゾリン誘導体 |
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| JP2000515114A JP2000515114A (ja) | 2000-11-14 |
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| JP4291413B2 true JP4291413B2 (ja) | 2009-07-08 |
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| JP52256897A Expired - Fee Related JP4291413B2 (ja) | 1995-12-18 | 1996-12-13 | キナゾリン誘導体 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2009007364A (ja) * | 1996-10-15 | 2009-01-15 | Astrazeneca Uk Ltd | キナゾリン誘導体 |
Families Citing this family (579)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6228871B1 (en) | 1995-07-10 | 2001-05-08 | Merck & Co., Inc. | Angiogenesis inhibitors |
| GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| WO1997030035A1 (en) | 1996-02-13 | 1997-08-21 | Zeneca Limited | Quinazoline derivatives as vegf inhibitors |
| PT885198E (pt) | 1996-03-05 | 2002-06-28 | Astrazeneca Ab | Derivados de 4-anilinoquinazolina |
| SK284073B6 (sk) | 1996-04-12 | 2004-09-08 | Warner-Lambert Company | Polycyklické zlúčeniny, ich použitie a farmaceutické kompozície na ich báze |
| GB9707800D0 (en) | 1996-05-06 | 1997-06-04 | Zeneca Ltd | Chemical compounds |
| ES2188957T3 (es) | 1996-06-27 | 2003-07-01 | Janssen Pharmaceutica Nv | N-(4-(heteroarilmetil)fenil)-heteroarilaminas. |
| US6809097B1 (en) | 1996-09-25 | 2004-10-26 | Zeneca Limited | Quinoline derivatives inhibiting the effect of growth factors such as VEGF |
| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| US6225318B1 (en) | 1996-10-17 | 2001-05-01 | Pfizer Inc | 4-aminoquinazolone derivatives |
| ZA986729B (en) * | 1997-07-29 | 1999-02-02 | Warner Lambert Co | Irreversible inhibitors of tyrosine kinases |
| AU8816298A (en) | 1997-08-22 | 1999-03-16 | Zeneca Limited | Oxindolylquinazoline derivatives as angiogenesis inhibitors |
| US6465484B1 (en) | 1997-09-26 | 2002-10-15 | Merck & Co., Inc. | Angiogenesis inhibitors |
| US6162804A (en) * | 1997-09-26 | 2000-12-19 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| FR2772763B1 (fr) * | 1997-12-24 | 2004-01-23 | Sod Conseils Rech Applic | Nouveaux analogues tetracycliques de camptothecines, leurs procedes de preparation, leur application comme medicaments et les compositions pharmaceutiques les contenant |
| JP4611524B2 (ja) | 1998-06-02 | 2011-01-12 | オーエスアイ・ファーマスーティカルズ・インコーポレーテッド | ピロロ[2,3d]ピリミジン組成物およびその使用 |
| US6878716B1 (en) | 1998-06-02 | 2005-04-12 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 receptor and uses thereof |
| US6686366B1 (en) | 1998-06-02 | 2004-02-03 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
| US7045519B2 (en) | 1998-06-19 | 2006-05-16 | Chiron Corporation | Inhibitors of glycogen synthase kinase 3 |
| US20040067227A1 (en) * | 2001-11-02 | 2004-04-08 | Goldstein Allan L. | Inhibition or reversal of skin aging by actin-sequestering peptides |
| UA71945C2 (en) | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
| JP3270834B2 (ja) | 1999-01-27 | 2002-04-02 | ファイザー・プロダクツ・インク | 抗がん剤として有用なヘテロ芳香族二環式誘導体 |
| BRPI0017548B8 (pt) * | 1999-02-10 | 2023-05-02 | Astrazeneca Ab | Composto |
| US7049410B2 (en) * | 1999-05-14 | 2006-05-23 | Majumdar Adhip P N | Antibodies to a novel EGF-receptor related protein (ERRP) |
| US6399743B1 (en) | 1999-05-14 | 2002-06-04 | Dept. Of Veterans Affairs | Isolation and characterization of a rat epidermal growth factor related protein |
| WO2000078735A1 (de) | 1999-06-21 | 2000-12-28 | Boehringer Ingelheim Pharma Kg | Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| US6921763B2 (en) | 1999-09-17 | 2005-07-26 | Abbott Laboratories | Pyrazolopyrimidines as therapeutic agents |
| HK1046688A1 (zh) | 1999-09-21 | 2003-01-24 | Astrazeneca Ab | 喹唑啉化合物和含有喹唑啉化合物的藥物組合物 |
| CZ20021009A3 (cs) * | 1999-09-21 | 2002-06-12 | Astrazeneca Ab | Deriváty chinazolinu, způsob jejich přípravy a jejich pouľití jako léčiv |
| SE9903544D0 (sv) | 1999-10-01 | 1999-10-01 | Astra Pharma Prod | Novel compounds |
| EE05330B1 (et) | 1999-11-05 | 2010-08-16 | Astrazeneca Ab | Kinasoliini derivaadid kui VEGF-i inhibiitorid |
| 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 |
| AU4903201A (en) | 1999-11-30 | 2001-07-03 | Parker Hughes Institute | Inhibitors of thrombin induced platelet aggregation |
| US6680322B2 (en) | 1999-12-02 | 2004-01-20 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 receptors and uses thereof |
| US6664252B2 (en) | 1999-12-02 | 2003-12-16 | Osi Pharmaceuticals, Inc. | 4-aminopyrrolo[2,3-d]pyrimidine compounds specific to adenosine A2a receptor and uses thereof |
| US7160890B2 (en) * | 1999-12-02 | 2007-01-09 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
| AU2001236698A1 (en) | 2000-02-07 | 2001-08-14 | Abbott Gesellschaft Mit Beschrankter Haftung & Company Kommanditgesellschaft | 2-benzothiazolyl urea derivatives and their use as protein kinase inhibitors |
| GB2359551A (en) | 2000-02-23 | 2001-08-29 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| AUPQ592100A0 (en) * | 2000-02-29 | 2000-03-23 | Council Of The Queensland Institute Of Medical Research, The | A method of treatment and prophylaxis |
| WO2001066099A2 (en) * | 2000-03-06 | 2001-09-13 | Astrazeneca Ab | Use of quinazoline derivatives as angiogenesis inhibitors |
| US20070021392A1 (en) * | 2000-03-31 | 2007-01-25 | Davis Peter D | Divided dose therapies with vascular damaging activity |
| GB0008269D0 (en) * | 2000-04-05 | 2000-05-24 | Astrazeneca Ab | Combination chemotherapy |
| CN1240688C (zh) * | 2000-04-07 | 2006-02-08 | 阿斯特拉曾尼卡有限公司 | 喹唑啉化合物 |
| RU2276151C2 (ru) * | 2000-06-06 | 2006-05-10 | Астразенека Аб | Хиназолиновые производные для лечения опухолей |
| UA73993C2 (uk) * | 2000-06-06 | 2005-10-17 | Астразенека Аб | Хіназолінові похідні для лікування пухлин та фармацевтична композиція |
| AR028948A1 (es) | 2000-06-20 | 2003-05-28 | Astrazeneca Ab | Compuestos novedosos |
| WO2002016352A1 (en) | 2000-08-21 | 2002-02-28 | Astrazeneca Ab | Quinazoline derivatives |
| DE10042058A1 (de) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| US6656946B2 (en) | 2000-08-26 | 2003-12-02 | Boehringer Ingelheim Pharma Kg | Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases |
| AU2001293233A1 (en) | 2000-09-01 | 2002-03-13 | Chiron Corporation | Aza heterocyclic derivatives and their therapeutic use |
| ES2302106T3 (es) | 2000-09-11 | 2008-07-01 | Novartis Vaccines And Diagnostics, Inc. | Procedimiento de preparacion de derivados de bencimidazol-2-il quinolina. |
| US20030028018A1 (en) * | 2000-09-11 | 2003-02-06 | Chiron Coporation | Quinolinone derivatives |
| SE0003828D0 (sv) | 2000-10-20 | 2000-10-20 | Astrazeneca Ab | Novel compounds |
| ATE502928T1 (de) | 2000-11-01 | 2011-04-15 | Millennium Pharm Inc | Stickstoffhaltige heterozyklische verbindungen und verfahren zu deren herstellung |
| WO2002043735A1 (en) * | 2000-11-29 | 2002-06-06 | Parker Hughes Institute | Inhibitors of thrombin induced platelet aggregation |
| US6673802B2 (en) | 2000-12-01 | 2004-01-06 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
| US6680324B2 (en) | 2000-12-01 | 2004-01-20 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 receptors and uses thereof |
| US7019012B2 (en) * | 2000-12-20 | 2006-03-28 | Boehringer Ingelheim International Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
| EP1343782B1 (en) | 2000-12-21 | 2009-05-06 | SmithKline Beecham Corporation | Pyrimidineamines as angiogenesis modulators |
| AR032028A1 (es) | 2001-01-05 | 2003-10-22 | Pfizer | Anticuerpos contra el receptor del factor de crecimiento similar a insulina |
| US20070050857A1 (en) * | 2001-02-28 | 2007-03-01 | Hayward Nick K | Method of treatment and prophylaxis |
| MXPA03008560A (es) | 2001-03-22 | 2004-06-30 | Abbot Gmbh & Co Kg | Pirazolopirimidinas como agentes terapeuticos. |
| WO2002092578A1 (en) * | 2001-05-14 | 2002-11-21 | Astrazeneca Ab | Quinazoline derivatives |
| US6995171B2 (en) | 2001-06-21 | 2006-02-07 | Agouron Pharmaceuticals, Inc. | Bicyclic pyrimidine and pyrimidine derivatives useful as anticancer agents |
| US7132427B2 (en) | 2001-06-21 | 2006-11-07 | Ariad Pharmaceuticals, Inc. | Quinazolines and uses thereof |
| JP4836368B2 (ja) * | 2001-08-30 | 2011-12-14 | 広栄化学工業株式会社 | メチルヒドロキシアルキルピリジン類の製造方法 |
| GB0126433D0 (en) * | 2001-11-03 | 2002-01-02 | Astrazeneca Ab | Compounds |
| JP2005515176A (ja) * | 2001-11-03 | 2005-05-26 | アストラゼネカ アクチボラグ | 抗腫瘍剤としてのキナゾリン誘導体 |
| AR039067A1 (es) | 2001-11-09 | 2005-02-09 | Pfizer Prod Inc | Anticuerpos para cd40 |
| ATE446298T1 (de) * | 2001-11-30 | 2009-11-15 | Osi Pharm Inc | Verbindungen, die für adenosin a1 und a3 rezeptoren spezifisch sind, und deren anwendungen |
| AU2002357621A1 (en) * | 2001-12-19 | 2003-06-30 | Ube Industries, Ltd. | Process for producing quinazolin-4-one and derivative thereof |
| CN1816551A (zh) * | 2001-12-20 | 2006-08-09 | Osi药物公司 | 吡咯并嘧啶A2b选择性拮抗剂化合物,它们的合成及用途 |
| AU2002366811B2 (en) | 2001-12-20 | 2009-01-15 | Osi Pharmaceuticals, Inc. | Pyrimidine A2B selective antagonist compounds, their synthesis and use |
| US8367824B2 (en) * | 2002-01-28 | 2013-02-05 | Ube Industries Ltd. | Process for producing quinazolin-4-one derivative |
| CN1625555A (zh) * | 2002-02-01 | 2005-06-08 | 阿斯特拉曾尼卡有限公司 | 喹唑啉化合物 |
| JP2005527511A (ja) | 2002-03-01 | 2005-09-15 | ファイザー インコーポレイテッド | 抗血管形成剤として有用なチエノピリジンのインドリル−尿素誘導体およびその使用法 |
| TWI324597B (en) * | 2002-03-28 | 2010-05-11 | Astrazeneca Ab | Quinazoline derivatives |
| US6924285B2 (en) | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
| 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 |
| 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 |
| US6936641B2 (en) * | 2002-06-25 | 2005-08-30 | Johnson & Johnson Vision Care, Inc. | Macromer forming catalysts |
| US7576074B2 (en) | 2002-07-15 | 2009-08-18 | Rice Kenneth D | Receptor-type kinase modulators and methods of use |
| GB0217431D0 (en) | 2002-07-27 | 2002-09-04 | Astrazeneca Ab | Novel compounds |
| US20050256157A1 (en) * | 2002-08-23 | 2005-11-17 | Chiron Corporation | Combination therapy with CHK1 inhibitors |
| BR0313743A (pt) * | 2002-08-23 | 2005-07-05 | Chiron Corp | Benzimidazol quinolinonas e usos destas |
| US7825132B2 (en) * | 2002-08-23 | 2010-11-02 | Novartis Vaccines And Diagnostics, Inc. | Inhibition of FGFR3 and treatment of multiple myeloma |
| AU2003257666A1 (en) * | 2002-08-23 | 2004-03-11 | Kirin Beer Kabushiki Kaisha | COMPOUND HAVING TGFss INHIBITORY ACTIVITY AND MEDICINAL COMPOSITION CONTAINING THE SAME |
| US7482355B2 (en) | 2002-08-24 | 2009-01-27 | Astrazeneca Ab | Pyrimidine derivatives as modulators of chemokine receptor activity |
| GB0221828D0 (en) | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| US7462623B2 (en) * | 2002-11-04 | 2008-12-09 | Astrazeneca Ab | Quinazoline derivatives as Src tyrosine kinase inhibitors |
| SG148864A1 (en) * | 2002-11-13 | 2009-01-29 | Chiron Corp | Methods of treating cancer and related methods |
| BR0317548A (pt) | 2002-12-19 | 2005-11-22 | Pfizer | Compostos de indazole e composições farmacêuticas para a inibição de proteìnas-cinases e métodos para o seu uso |
| PT1578755E (pt) | 2002-12-24 | 2007-10-19 | Astrazeneca Ab | Derivados de fosfonooxiquinazolina e sua utilização farmacêutica |
| 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 |
| DK1603570T5 (da) | 2003-02-26 | 2013-12-09 | Sugen Inc | Aminoheteroarylforbindelser som proteinkinaseinhibitorer |
| GB0309009D0 (en) * | 2003-04-22 | 2003-05-28 | Astrazeneca Ab | Quinazoline derivatives |
| GB0309850D0 (en) | 2003-04-30 | 2003-06-04 | Astrazeneca Ab | Quinazoline derivatives |
| SE0301569D0 (sv) | 2003-05-27 | 2003-05-27 | Astrazeneca Ab | Novel compounds |
| GB0317665D0 (en) | 2003-07-29 | 2003-09-03 | Astrazeneca Ab | Qinazoline derivatives |
| HN2004000285A (es) | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
| GB0318423D0 (en) * | 2003-08-06 | 2003-09-10 | Astrazeneca Ab | Chemical compounds |
| PL1660057T3 (pl) | 2003-08-27 | 2012-10-31 | Ophthotech Corp | Terapia łączona do leczenia zaburzeń związanych z neowaskularyzacją gałki ocznej |
| 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 |
| AR045563A1 (es) | 2003-09-10 | 2005-11-02 | Warner Lambert Co | Anticuerpos dirigidos a m-csf |
| AU2004272350A1 (en) * | 2003-09-16 | 2005-03-24 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
| US7569577B2 (en) | 2003-09-16 | 2009-08-04 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
| GB0321648D0 (en) * | 2003-09-16 | 2003-10-15 | Astrazeneca Ab | Quinazoline derivatives |
| DE602004004811T2 (de) * | 2003-09-19 | 2007-11-22 | Astrazeneca Ab | Chinazolinderivate |
| JP4036885B2 (ja) * | 2003-09-19 | 2008-01-23 | アストラゼネカ アクチボラグ | キナゾリン誘導体 |
| US20070043010A1 (en) * | 2003-09-25 | 2007-02-22 | Astrazeneca Uk Limited | Quinazoline derivatives |
| WO2005030140A2 (en) | 2003-09-26 | 2005-04-07 | Exelixis, Inc. | C-met modulators and methods of use |
| US7456189B2 (en) | 2003-09-30 | 2008-11-25 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation |
| KR100872204B1 (ko) | 2003-10-15 | 2008-12-09 | 오에스아이 파마슈티컬스, 인코포레이티드 | 이미다조피라진 티로신 키나제 억제제 |
| KR101167573B1 (ko) * | 2003-11-07 | 2012-07-30 | 노바티스 백신즈 앤드 다이아그노스틱스 인코포레이티드 | 개선된 약학적 성질을 갖는 퀴놀리논 화합물의 약학적으로허용가능한 염 |
| GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
| JP4869075B2 (ja) | 2003-11-19 | 2012-02-01 | アレイ バイオファーマ、インコーポレイテッド | Mekの複素環阻害剤及びその使用方法 |
| GB0328243D0 (en) | 2003-12-05 | 2004-01-07 | Astrazeneca Ab | Methods |
| AP2006003619A0 (en) | 2003-12-23 | 2006-06-30 | Pfizer | Novel quinoline derivatives |
| GB0330002D0 (en) | 2003-12-24 | 2004-01-28 | Astrazeneca Ab | Quinazoline derivatives |
| DE602004031777D1 (en) | 2004-01-05 | 2011-04-21 | Astrazeneca Ab | Thiophenderivate als chk-1-inhibitoren |
| CN1933839A (zh) * | 2004-01-23 | 2007-03-21 | 安进公司 | 化合物和使用方法 |
| WO2005082340A2 (en) * | 2004-02-20 | 2005-09-09 | Chiron Corporation | Modulation of inflammatory and metastatic processes |
| WO2005080377A1 (ja) * | 2004-02-20 | 2005-09-01 | Kirin Beer Kabushiki Kaisha | TGFβ阻害活性を有する化合物およびそれを含んでなる医薬組成物 |
| DE602005014964D1 (de) | 2004-04-02 | 2009-07-30 | Osi Pharm Inc | Mit einem 6,6-bicyclischen ring substituierte heterobicyclische proteinkinaseinhibitoren |
| ME01267B (me) | 2004-05-06 | 2013-06-20 | Warner Lambert Co | 4-fenilaminokinazolin-6-ilamidi |
| CA2567832A1 (en) * | 2004-06-04 | 2005-12-15 | Astrazeneca Ab | Quinazoline derivatives as erbb receptor tyrosine kinases |
| SE0401657D0 (sv) | 2004-06-24 | 2004-06-24 | Astrazeneca Ab | Chemical compounds |
| BRPI0513200A (pt) | 2004-07-16 | 2008-04-29 | Pfizer Prod Inc | uso de um anticorpo anti-igf-1r na preparação de um medicamento para tratamento combinado para malignidades não-hematológicas |
| TW200613306A (en) | 2004-07-20 | 2006-05-01 | Osi Pharm Inc | Imidazotriazines as protein kinase inhibitors |
| JP4242911B2 (ja) | 2004-08-26 | 2009-03-25 | ファイザー・インク | プロテインキナーゼ阻害薬としてのエナンチオピュアなアミノヘテロアリール化合物 |
| ME01620B (me) | 2004-08-28 | 2014-09-20 | Astrazeneca Ab | Pirimidin sulfonamidni derivati kao modulatori hemokinskih receptora |
| JP2008521900A (ja) | 2004-11-30 | 2008-06-26 | アムジエン・インコーポレーテツド | キノリン及びキナゾリン類似体並びにがん治療のための医薬としてのその使用 |
| CN101124228B (zh) | 2004-12-14 | 2011-06-15 | 阿斯利康(瑞典)有限公司 | 用作抗肿瘤药物的吡唑并嘧啶化合物 |
| HRP20110859T1 (hr) | 2004-12-21 | 2011-12-31 | Medimmune Limited | Protutijela usmjerena na angiopoietin-2 i njihova upotreba |
| GB0428526D0 (en) | 2004-12-30 | 2005-02-09 | Novartis Ag | Organic compounds |
| ES2374570T3 (es) * | 2005-01-27 | 2012-02-17 | Novartis Vaccines And Diagnostics, Inc. | Tratamiento de tumores metastalizados. |
| PT1846394E (pt) | 2005-02-04 | 2012-01-05 | Astrazeneca Ab | Derivados de pirazolilaminopiridina úteis como inibidores da quinase |
| CN101163684B (zh) * | 2005-02-23 | 2012-08-29 | 盐野义制药株式会社 | 具有酪氨酸激酶抑制作用的喹唑啉衍生物 |
| EP1856095B1 (en) * | 2005-02-26 | 2011-08-24 | AstraZeneca AB | Quinazoline derivatives as tyrosine kinase inhibitors |
| GB0504474D0 (en) * | 2005-03-04 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
| RU2413735C2 (ru) | 2005-03-31 | 2011-03-10 | Эдженсис, Инк. | Антитела и родственные молекулы, связывающиеся с белками 161p2f10b |
| NZ562234A (en) | 2005-04-26 | 2009-09-25 | Pfizer | P-cadherin antibodies |
| JO2787B1 (en) | 2005-04-27 | 2014-03-15 | امجين إنك, | Alternative amide derivatives and methods of use |
| GB0508717D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
| GB0508715D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
| CN1858040B (zh) * | 2005-05-08 | 2011-04-06 | 中国科学院上海药物研究所 | 5,8-二取代喹唑啉及其制备方法和用途 |
| US8299081B2 (en) | 2005-05-13 | 2012-10-30 | Novartis Ag | Methods for treating drug resistant cancer |
| CN101223157B (zh) * | 2005-05-17 | 2013-03-06 | 诺瓦提斯公司 | 合成杂环化合物的方法 |
| RU2500673C2 (ru) | 2005-05-18 | 2013-12-10 | Астразенека Аб | Гетероциклические ингибиторы мек и способы их применения |
| EP1904480A2 (en) | 2005-05-23 | 2008-04-02 | Novartis Pharma AG | Crystalline and other forms of 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1h-benzimidazol-2-yl]-1h-quinolin-2-one lactic acid salts |
| RU2291706C1 (ru) * | 2005-06-21 | 2007-01-20 | Автономная некоммерческая организация Научно-технический центр "Фармбиопресс" | Применение флаволигнанов для подавления избыточной и патологической пролиферации эндотелия сосудов |
| JP2009501793A (ja) | 2005-07-21 | 2009-01-22 | アストラゼネカ・アクチエボラーグ | 新規ピペリジン誘導体 |
| TW200738634A (en) | 2005-08-02 | 2007-10-16 | Astrazeneca Ab | New salt |
| US7566721B2 (en) * | 2005-08-08 | 2009-07-28 | Osi Pharmaceuticals, Inc. | Substituted thienol[2,3-d]pyrimidines as kinase inhibitors |
| TW200738658A (en) | 2005-08-09 | 2007-10-16 | Astrazeneca Ab | Novel compounds |
| DK1933871T3 (da) | 2005-09-07 | 2013-07-08 | Amgen Fremont Inc | Humane monoklonale antistoffer mod activin-receptor-lignende kinase-1 |
| US20090239861A1 (en) * | 2005-09-20 | 2009-09-24 | Robert Hugh Bradbury | Quinazoline derivatives as anticancer agents |
| US7820683B2 (en) | 2005-09-20 | 2010-10-26 | Astrazeneca Ab | 4-(1H-indazol-5-yl-amino)-quinazoline compounds as erbB receptor tyrosine kinase inhibitors for the treatment of cancer |
| AU2006292278B2 (en) | 2005-09-20 | 2012-03-08 | Osi Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| WO2007034916A1 (ja) | 2005-09-22 | 2007-03-29 | Dainippon Sumitomo Pharma Co., Ltd. | 新規アデニン化合物 |
| EP1939198A4 (en) | 2005-09-22 | 2012-02-15 | Dainippon Sumitomo Pharma Co | NEW ADENINE CONNECTION |
| EP1939201A4 (en) | 2005-09-22 | 2010-06-16 | Dainippon Sumitomo Pharma Co | NEW ADENINE CONNECTION |
| EP1939199A4 (en) | 2005-09-22 | 2010-10-20 | Dainippon Sumitomo Pharma Co | NEW ADENINE CONNECTION |
| GB0519879D0 (en) | 2005-09-30 | 2005-11-09 | Astrazeneca Ab | Chemical process |
| EP1937632A1 (en) | 2005-10-06 | 2008-07-02 | Astra Zeneca AB | Novel compounds |
| WO2007049041A1 (en) | 2005-10-28 | 2007-05-03 | Astrazeneca Ab | 4- (3-aminopyrazole) pyrimidine derivatives for use as tyrosine kinase inhibitors in the treatment of cancer |
| JP5688877B2 (ja) | 2005-11-11 | 2015-03-25 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌疾患の治療用キナゾリン誘導体 |
| PL2090575T3 (pl) | 2005-11-15 | 2011-09-30 | Array Biopharma Inc | Sposoby i związki pośrednie do otrzymywania pochodnych N4-fenylo-chinazolino-4-aminy |
| JP2009517481A (ja) | 2005-11-29 | 2009-04-30 | ノバルティス アクチエンゲゼルシャフト | キノリノンの製剤 |
| AR057960A1 (es) | 2005-12-02 | 2007-12-26 | Osi Pharm Inc | Inhibidores de proteina quinasa biciclicos |
| ATE443053T1 (de) * | 2005-12-02 | 2009-10-15 | Astrazeneca Ab | Als inhibitoren von erbb-tyrosinkinase verwendete chinazoleinderivate |
| WO2007063291A1 (en) * | 2005-12-02 | 2007-06-07 | Astrazeneca Ab | 4-anilino-substituted quinazoline derivatives as tyrosine kinase inhibitors |
| TW200730512A (en) | 2005-12-12 | 2007-08-16 | Astrazeneca Ab | Novel compounds |
| US7939637B2 (en) | 2005-12-13 | 2011-05-10 | Medimmune Limited | Insulin-like growth factor antibodies and uses thereof |
| ATE545637T1 (de) | 2005-12-15 | 2012-03-15 | Astrazeneca Ab | Substituierte diphenylether, -amine, -sulfide und methane zur behandlung von atemwegserkrankungen |
| US8575164B2 (en) * | 2005-12-19 | 2013-11-05 | OSI Pharmaceuticals, LLC | Combination cancer therapy |
| US20070231298A1 (en) * | 2006-03-31 | 2007-10-04 | Cell Genesys, Inc. | Cytokine-expressing cancer immunotherapy combinations |
| TW200813091A (en) | 2006-04-10 | 2008-03-16 | Amgen Fremont Inc | Targeted binding agents directed to uPAR and uses thereof |
| EP2258700A1 (en) | 2006-05-09 | 2010-12-08 | Pfizer Products Inc. | Cycloalkylamino acid derivatives and pharmaceutical compositions thereof |
| WO2007138282A2 (en) | 2006-05-26 | 2007-12-06 | Astrazeneca Ab | Bi-aryl or aryl-heteroaryl substituted indoles |
| CL2007002225A1 (es) | 2006-08-03 | 2008-04-18 | Astrazeneca Ab | Agente de union especifico para un receptor del factor de crecimiento derivado de plaquetas (pdgfr-alfa); molecula de acido nucleico que lo codifica; vector y celula huesped que la comprenden; conjugado que comprende al agente; y uso del agente de un |
| DE102006037478A1 (de) | 2006-08-10 | 2008-02-14 | Merck Patent Gmbh | 2-(Heterocyclylbenzyl)-pyridazinonderivate |
| AU2007287430B2 (en) | 2006-08-23 | 2011-07-21 | Kudos Pharmaceuticals Limited | 2-methylmorpholine pyrido-, pyrazo- and pyrimido-pyrimidine derivatives as mTOR inhibitors |
| SI2068880T1 (sl) * | 2006-09-18 | 2012-08-31 | Boehringer Ingelheim Int | Postopek za zdravljenje raka, ki vsebuje mutacije EGFR |
| US7851623B2 (en) * | 2006-11-02 | 2010-12-14 | Astrazeneca Ab | Chemical process |
| EP1921070A1 (de) | 2006-11-10 | 2008-05-14 | Boehringer Ingelheim Pharma GmbH & Co. KG | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstelllung |
| TW200825084A (en) | 2006-11-14 | 2008-06-16 | Astrazeneca Ab | New compounds 521 |
| US7799954B2 (en) | 2006-11-17 | 2010-09-21 | Abraxis Bioscience, Llc | Dicarbonyl derivatives and methods of use |
| TW200831528A (en) | 2006-11-30 | 2008-08-01 | Astrazeneca Ab | Compounds |
| CA2672446A1 (en) | 2006-12-19 | 2008-06-26 | Astrazeneca Ab | Quinuclidinol derivatives as muscarinic receptor antagonists |
| CL2008000191A1 (es) | 2007-01-25 | 2008-08-22 | Astrazeneca Ab | Compuestos derivados de 4-amino-cinnotina-3-carboxamida; inhibidores de csf-1r quinasa; su proceso de preparacion; y su uso para tratar el cancer. |
| EA200901041A1 (ru) | 2007-02-06 | 2010-02-26 | Бёрингер Ингельхайм Интернациональ Гмбх | Бициклические гетероциклы, содержащие эти соединения лекарственные средства, их применение и способ их получения |
| US20080190689A1 (en) * | 2007-02-12 | 2008-08-14 | Ballard Ebbin C | Inserts for engine exhaust systems |
| US8148532B2 (en) | 2007-03-14 | 2012-04-03 | Guoqing Paul Chen | Spiro substituted compounds as angiogenesis inhibitors |
| JPWO2008114819A1 (ja) | 2007-03-20 | 2010-07-08 | 大日本住友製薬株式会社 | 新規アデニン化合物 |
| AR065784A1 (es) | 2007-03-20 | 2009-07-01 | Dainippon Sumitomo Pharma Co | Derivados de 8-oxo adenina,medicamentos que los contienen y usos como agentes terapeuticos para enfermedades alergicas, antivirales o antibacterianas. |
| UA99459C2 (en) | 2007-05-04 | 2012-08-27 | Астразенека Аб | 9-(pyrazol-3-yl)- 9h-purine-2-amine and 3-(pyraz0l-3-yl)-3h-imidazo[4,5-b]pyridin-5-amine derivatives and their use for the treatment of cancer |
| DE102007025717A1 (de) | 2007-06-01 | 2008-12-11 | Merck Patent Gmbh | Arylether-pyridazinonderivate |
| DE102007025718A1 (de) | 2007-06-01 | 2008-12-04 | Merck Patent Gmbh | Pyridazinonderivate |
| DE102007026341A1 (de) | 2007-06-06 | 2008-12-11 | Merck Patent Gmbh | Benzoxazolonderivate |
| UA100983C2 (ru) | 2007-07-05 | 2013-02-25 | Астразенека Аб | Бифенилоксипропановая кислота как модулятор crth2 и интермедиаты |
| DE102007032507A1 (de) | 2007-07-12 | 2009-04-02 | Merck Patent Gmbh | Pyridazinonderivate |
| DE102007038957A1 (de) | 2007-08-17 | 2009-02-19 | Merck Patent Gmbh | 6-Thioxo-pyridazinderivate |
| DE102007041115A1 (de) | 2007-08-30 | 2009-03-05 | Merck Patent Gmbh | Thiadiazinonderivate |
| PL2185574T3 (pl) | 2007-09-07 | 2013-09-30 | Agensys Inc | Przeciwciała i powiązane cząsteczki, które wiążą się do białek 24P4C12 |
| EA201000436A1 (ru) | 2007-10-04 | 2010-10-29 | Астразенека Аб | Стероидные [3,2-с]пиразольные соединения, обладающие глюкокортикоидной активностью |
| JP4705695B2 (ja) | 2007-10-11 | 2011-06-22 | アストラゼネカ アクチボラグ | プロテインキナーゼb阻害剤としてのピロロ[2,3−d]ピリミジン誘導体 |
| PL2222675T3 (pl) | 2007-12-19 | 2014-02-28 | Genentech Inc | 5-anilinoimidazopirydyny i sposoby zastosowania |
| US8092804B2 (en) | 2007-12-21 | 2012-01-10 | Medimmune Limited | Binding members for interleukin-4 receptor alpha (IL-4Rα)-173 |
| EP3211010A1 (en) | 2007-12-21 | 2017-08-30 | Medimmune Limited | Binding members for interleukin-4 receptor alpha (il-4r) - 173 |
| KR20100099185A (ko) | 2007-12-21 | 2010-09-10 | 제넨테크, 인크. | 아자인돌리진 및 이용 방법 |
| DE102007061963A1 (de) | 2007-12-21 | 2009-06-25 | Merck Patent Gmbh | Pyridazinonderivate |
| JP2011510018A (ja) * | 2008-01-18 | 2011-03-31 | オーエスアイ・フアーマスーテイカルズ・インコーポレーテツド | 癌治療のためのイミダゾピラジノール誘導体 |
| US8609673B2 (en) * | 2008-01-22 | 2013-12-17 | Concert Pharmaceuticals, Inc. | Vandetanib derivatives |
| EP2242493B1 (en) * | 2008-01-22 | 2013-06-05 | Concert Pharmaceuticals Inc. | Derivatives of gefitinib |
| RS52573B (sr) | 2008-02-07 | 2013-04-30 | Boehringer Ingelheim International Gmbh | Spirociklični heterocikli, lekovi koji sadrže navedeno jedinjenje, njihova primena i postupak za njihovu proizvodnju |
| US8735584B2 (en) | 2008-02-28 | 2014-05-27 | Merck Patent Gmbh | Protein kinase inhibitors and use thereof |
| DE102008019907A1 (de) | 2008-04-21 | 2009-10-22 | Merck Patent Gmbh | Pyridazinonderivate |
| BRPI0912170A2 (pt) | 2008-05-13 | 2015-10-13 | Astrazeneca Ab | composto, forma a, processo para a preparação da mesma, composição farmacêutica, uso de um composto, e, método para tratar um câncer em um animal de sangue quente |
| EP2283020B8 (en) * | 2008-05-19 | 2012-12-12 | OSI Pharmaceuticals, LLC | Substituted imidazopyr-and imidazotri-azines |
| CA2721065C (en) | 2008-05-27 | 2016-09-27 | Astrazeneca Ab | Phenoxypyridinylamide derivatives and their use as pde4 inhibitors |
| DE102008025750A1 (de) | 2008-05-29 | 2009-12-03 | Merck Patent Gmbh | Dihydropyrazolderivate |
| DE102008028905A1 (de) | 2008-06-18 | 2009-12-24 | Merck Patent Gmbh | 3-(3-Pyrimidin-2-yl-benzyl)-[1,2,4]triazolo[4,3-b]pyridazinderivate |
| DE102008029734A1 (de) | 2008-06-23 | 2009-12-24 | Merck Patent Gmbh | Thiazolyl-piperidinderivate |
| UY31952A (es) | 2008-07-02 | 2010-01-29 | Astrazeneca Ab | 5-metilideno-1,3-tiazolidina-2,4-dionas sustituidas como inhibidores de quinasa pim |
| CA2733153C (en) | 2008-08-08 | 2016-11-08 | Boehringer Ingelheim International Gmbh | Cyclohexyloxy substituted heterocycles, pharmaceutical compositions containing these compounds and processes for preparing them |
| DE102008037790A1 (de) | 2008-08-14 | 2010-02-18 | Merck Patent Gmbh | Bicyclische Triazolderivate |
| DE102008038221A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | 7-Azaindolderivate |
| US8211911B2 (en) | 2008-08-19 | 2012-07-03 | Guoqing Paul Chen | Compounds as kinase inhibitors |
| MX2011002837A (es) | 2008-09-19 | 2011-07-29 | Medimmune Llc | Anticuerpos dirigidos al ligando tipo delta 4 (dll4) y usos de los mismos. |
| CA2737597C (en) | 2008-10-16 | 2017-03-14 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Fully human antibodies to high molecular weight-melanoma associated antigen and uses thereof |
| DE102008052943A1 (de) | 2008-10-23 | 2010-04-29 | Merck Patent Gmbh | Azaindolderivate |
| WO2010067102A1 (en) | 2008-12-09 | 2010-06-17 | Astrazeneca Ab | Diazaspiro [5.5] undecane derivatives and related compounds as muscarinic-receptor antagonists and beta-adrenoreceptor agonists for the treatment of pulmonary disorders |
| US9012495B2 (en) | 2008-12-11 | 2015-04-21 | Axcentua Pharmaceuticals Ab | Crystalline forms of genistein |
| US7863325B2 (en) | 2008-12-11 | 2011-01-04 | Axcentua Pharmaceuticals Ab | Crystalline genistein sodium salt dihydrate |
| US20100152197A1 (en) | 2008-12-15 | 2010-06-17 | Astrazeneca Ab | (4-tert-butylpiperazin-2-yl)(piperazin-1-yl)methanone-n-carboxamide derivatives |
| AU2009333653B2 (en) | 2008-12-17 | 2015-09-10 | Merck Patent Gmbh | C-ring modified tricyclic benzonaphthiridinone protein kinase inhibitors and use thereof |
| DE102008063667A1 (de) | 2008-12-18 | 2010-07-01 | Merck Patent Gmbh | 3-(3-Pyrimidin-2-yl-benzyl)-°[1,2,4]triazolo[4,3-b]pyrimidin-derivate |
| AU2009336040B2 (en) | 2008-12-18 | 2015-07-16 | Merck Patent Gmbh | Tricyclic azaindoles |
| DE102008062826A1 (de) | 2008-12-23 | 2010-07-01 | Merck Patent Gmbh | Pyridazinonderivate |
| AU2009331528A1 (en) | 2008-12-23 | 2011-08-11 | Astrazeneca Ab | Targeted binding agents directed to alpha5beta1 and uses thereof |
| DE102008062825A1 (de) | 2008-12-23 | 2010-06-24 | Merck Patent Gmbh | 3-(3-Pyrimidin-2-yl-benzyl)-[1,2,4]triazolo [4,3-b]pyridazin-derivate |
| DE102009003975A1 (de) | 2009-01-07 | 2010-07-08 | Merck Patent Gmbh | Benzothiazolonderivate |
| DE102009003954A1 (de) | 2009-01-07 | 2010-07-08 | Merck Patent Gmbh | Pyridazinonderivate |
| DE102009004061A1 (de) | 2009-01-08 | 2010-07-15 | Merck Patent Gmbh | Pyridazinonderivate |
| DK2387563T4 (da) | 2009-01-16 | 2022-07-18 | Exelixis Inc | Malatsalt af n-(4-{ [ 6, 7-bis(methyloxy)quinolin-4-yl]oxy}phenyl-n'-(4-fluorphenyl)cyclopropan-1,1-dicarboxamid, og krystallinske former deraf til behandling af cancer |
| US8426402B2 (en) | 2009-02-05 | 2013-04-23 | Immunogen, Inc. | Benzodiazepine derivatives |
| WO2010089580A1 (en) | 2009-02-06 | 2010-08-12 | Astrazeneca Ab | Use of a mct1 inhibitor in the treatment of cancers expressing mct1 over mct4 |
| EP2393814A1 (en) | 2009-02-09 | 2011-12-14 | SuperGen, Inc. | Pyrrolopyrimidinyl axl kinase inhibitors |
| EA019647B1 (ru) | 2009-02-10 | 2014-05-30 | Астразенека Аб | ПРОИЗВОДНЫЕ ТРИАЗОЛО[4,3-b]ПИРИДАЗИНА И ИХ ПРИМЕНЕНИЕ ДЛЯ ЛЕЧЕНИЯ РАКА ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ |
| EP2400985A2 (en) | 2009-02-25 | 2012-01-04 | OSI Pharmaceuticals, LLC | Combination of an either an anti-igf-1r antibody or an igf binding protein and a small molecule igf-1r kinase inhibitor |
| JP2012519170A (ja) | 2009-02-26 | 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 | 生体内の腫瘍細胞のemtステータスをモニターするためのinsitu法 |
| 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 |
| 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 |
| WO2010098866A1 (en) | 2009-02-27 | 2010-09-02 | Supergen, Inc. | Cyclopentathiophene/cyclohexathiophene dna methyltransferase inhibitors |
| 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 |
| GB0905127D0 (en) | 2009-03-25 | 2009-05-06 | Pharminox Ltd | Novel prodrugs |
| UY32520A (es) | 2009-04-03 | 2010-10-29 | Astrazeneca Ab | Compuestos que tienen actividad agonista del receptor de glucocorticoesteroides |
| EP2421837A1 (en) | 2009-04-20 | 2012-02-29 | OSI Pharmaceuticals, LLC | Preparation of c-pyrazine-methylamines |
| JP2012526138A (ja) * | 2009-05-07 | 2012-10-25 | オーエスアイ・ファーマシューティカルズ,エルエルシー | 副腎皮質癌を治療するためのosi−906の使用 |
| RU2404783C1 (ru) * | 2009-05-20 | 2010-11-27 | Общество с ограниченной ответственностью "Лигфарм" | Антиангиогенное лекарственное средство и способ его получения |
| US8389580B2 (en) | 2009-06-02 | 2013-03-05 | Duke University | Arylcyclopropylamines and methods of use |
| US20100317593A1 (en) | 2009-06-12 | 2010-12-16 | Astrazeneca Ab | 2,3-dihydro-1h-indene compounds |
| JP5963672B2 (ja) | 2009-07-06 | 2016-08-03 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Bibw2992、その塩及びこの活性成分を含む固体医薬製剤の乾燥方法 |
| CA2766403A1 (en) | 2009-07-13 | 2011-01-20 | Genentech, Inc. | Diagnostic methods and compositions for treatment of cancer |
| GB0913342D0 (en) | 2009-07-31 | 2009-09-16 | Astrazeneca Ab | Compounds - 801 |
| EP2459191A1 (en) | 2009-07-31 | 2012-06-06 | OSI Pharmaceuticals, LLC | Mtor inhibitor and angiogenesis inhibitor combination therapy |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| EP2473500A2 (en) | 2009-09-01 | 2012-07-11 | Pfizer Inc. | Benzimidazole derivatives |
| RU2012114094A (ru) | 2009-09-11 | 2013-10-20 | Дженентек, Инк. | Способ идентификации пациента с увеличенной вероятностью ответа на противораковый агент |
| WO2011033006A1 (en) | 2009-09-17 | 2011-03-24 | F. Hoffmann-La Roche Ag | Methods and compositions for diagnostics use in cancer patients |
| DE102009043260A1 (de) | 2009-09-28 | 2011-04-28 | Merck Patent Gmbh | Pyridinyl-imidazolonderivate |
| MX2012003644A (es) | 2009-10-02 | 2012-04-30 | Astrazeneca Ab | Compuestos de 2-piridona empleados como inhibidores de la elastasa neutrofila. |
| DE102009049679A1 (de) | 2009-10-19 | 2011-04-21 | Merck Patent Gmbh | Pyrazolopyrimidinderivate |
| WO2011048409A1 (en) | 2009-10-20 | 2011-04-28 | Astrazeneca Ab | Cyclic amine derivatives having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity |
| US8399460B2 (en) | 2009-10-27 | 2013-03-19 | Astrazeneca Ab | Chromenone derivatives |
| JP5806672B2 (ja) | 2009-10-30 | 2015-11-10 | ドメイン・セラピューティクス | 新規オキシム誘導体及び代謝型グルタミン酸受容体のアロステリック調節因子としての利用 |
| BR112012011518B8 (pt) | 2009-11-18 | 2023-01-10 | Astrazeneca Ab | Compostos, composição farmacêutica, kit e usos de um composto |
| NZ599405A (en) | 2009-11-24 | 2014-09-26 | Medimmune Ltd | Targeted binding agents against b7-h1 |
| WO2011068233A1 (en) | 2009-12-03 | 2011-06-09 | Dainippon Sumitomo Pharma Co., Ltd. | Imidazoquinolines which act via toll - like receptors (tlr) |
| JP2013513628A (ja) | 2009-12-14 | 2013-04-22 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | スフィンゴシンキナーゼの阻害薬 |
| DE102009058280A1 (de) | 2009-12-14 | 2011-06-16 | Merck Patent Gmbh | Thiazolderivate |
| WO2011073521A1 (en) | 2009-12-15 | 2011-06-23 | Petri Salven | Methods for enriching adult-derived endothelial progenitor cells and uses thereof |
| JP2013514287A (ja) | 2009-12-17 | 2013-04-25 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | スフィンゴシンキナーゼの阻害薬 |
| ES2857626T3 (es) | 2010-01-15 | 2021-09-29 | Suzhou Neupharma Co Ltd | Ciertas entidades químicas, composiciones y métodos |
| WO2011089416A1 (en) | 2010-01-19 | 2011-07-28 | Astrazeneca Ab | Pyrazine derivatives |
| WO2011095807A1 (en) | 2010-02-07 | 2011-08-11 | Astrazeneca Ab | Combinations of mek and hh inhibitors |
| US9173961B2 (en) | 2010-02-10 | 2015-11-03 | Immunogen, Inc. | CD20 antibodies and uses thereof |
| CA3024216C (en) | 2010-02-12 | 2021-03-30 | Pfizer Inc. | Salts and polymorphs of 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6h-azepino[5,4,3-cd]indol-6-one |
| US20110217309A1 (en) | 2010-03-03 | 2011-09-08 | Buck Elizabeth A | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| AU2011223643A1 (en) | 2010-03-03 | 2012-06-28 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| WO2011114148A1 (en) | 2010-03-17 | 2011-09-22 | Astrazeneca Ab | 4h- [1, 2, 4] triazolo [5, 1 -b] pyrimidin-7 -one derivatives as ccr2b receptor antagonists |
| WO2011153224A2 (en) | 2010-06-02 | 2011-12-08 | Genentech, Inc. | Diagnostic methods and compositions for treatment of cancer |
| WO2011154677A1 (en) | 2010-06-09 | 2011-12-15 | Astrazeneca Ab | Substituted n-[1-cyano-2-(phenyl)ethyl] 1-aminocycloalk-1-ylcarboxamide compounds - 760 |
| GB201009801D0 (en) | 2010-06-11 | 2010-07-21 | Astrazeneca Ab | Compounds 950 |
| ES2611479T3 (es) | 2010-06-16 | 2017-05-09 | University Of Pittsburgh- Of The Commonwealth System Of Higher Education | Anticuerpos contra endoplasmina y su uso |
| JP2013538338A (ja) | 2010-07-19 | 2013-10-10 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 抗癌治療への応答可能性の増大した患者を同定する方法 |
| SG10201505593VA (en) | 2010-07-19 | 2015-09-29 | Hoffmann La Roche | Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy |
| ES2979168T3 (es) | 2010-07-23 | 2024-09-24 | Univ Boston | Inhibidores anti-DEspR como productos terapéuticos para inhibición de angiogénesis patológica e invasividad de células tumorales y para imagenología molecular y administración dirigida |
| TW201219383A (en) | 2010-08-02 | 2012-05-16 | Astrazeneca Ab | Chemical compounds |
| TWI535712B (zh) | 2010-08-06 | 2016-06-01 | 阿斯特捷利康公司 | 化合物 |
| DE102010034699A1 (de) | 2010-08-18 | 2012-02-23 | Merck Patent Gmbh | Pyrimidinderivate |
| CN102656179B (zh) | 2010-08-28 | 2015-07-29 | 苏州润新生物科技有限公司 | 蟾蜍灵衍生物、其药物组合物及用途 |
| WO2012042421A1 (en) | 2010-09-29 | 2012-04-05 | Pfizer Inc. | Method of treating abnormal cell growth |
| GB201016442D0 (en) | 2010-09-30 | 2010-11-17 | Pharminox Ltd | Novel acridine derivatives |
| CA2813162C (en) | 2010-10-20 | 2015-06-16 | Pfizer Inc. | Pyridine-2- derivatives as smoothened receptor modulators |
| DE102010048800A1 (de) | 2010-10-20 | 2012-05-10 | Merck Patent Gmbh | Chinoxalinderivate |
| DE102010049595A1 (de) | 2010-10-26 | 2012-04-26 | Merck Patent Gmbh | Chinazolinderivate |
| WO2012066336A1 (en) | 2010-11-19 | 2012-05-24 | Astrazeneca Ab | Benzylamine compounds as toll -like receptor 7 agonists |
| WO2012066335A1 (en) | 2010-11-19 | 2012-05-24 | Astrazeneca Ab | Phenol compounds als toll -like receptor 7 agonists |
| WO2012067269A1 (en) | 2010-11-19 | 2012-05-24 | Dainippon Sumitomo Pharma Co., Ltd. | Aminoalkoxyphenyl compounds and their use in the treatment of disease |
| EP2640716A1 (en) | 2010-11-19 | 2013-09-25 | Dainippon Sumitomo Pharma Co., Ltd. | Cyclic amide compounds and their use in the treatment of disease |
| WO2012080728A1 (en) | 2010-12-16 | 2012-06-21 | Astrazeneca Ab | Imidazo [4, 5 -c] quinolin- 1 -yl derivative useful in therapy |
| JP5978226B2 (ja) | 2010-12-17 | 2016-08-24 | 大日本住友製薬株式会社 | プリン誘導体 |
| US9255144B2 (en) | 2010-12-20 | 2016-02-09 | Medimmune Limited | Anti-IL-18 antibodies and their uses |
| EP2670763B1 (en) | 2011-02-02 | 2018-08-01 | Suzhou Neupharma Co., Ltd | Certain chemical entities, compositions, and methods |
| IL279304B (en) | 2011-02-15 | 2022-07-01 | Immunogen Inc | Method for producing an indolinobenzodiazepine |
| ES2691673T3 (es) | 2011-02-17 | 2018-11-28 | Cancer Therapeutics Crc Pty Limited | Inhibidores de Fak |
| JP5937112B2 (ja) | 2011-02-17 | 2016-06-22 | カンサー・セラピューティクス・シーアールシー・プロプライエタリー・リミテッドCancer Therapeutics Crc Pty Limited | 選択的fak阻害剤 |
| WO2012116040A1 (en) | 2011-02-22 | 2012-08-30 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma |
| GB201104267D0 (en) | 2011-03-14 | 2011-04-27 | Cancer Rec Tech Ltd | Pyrrolopyridineamino derivatives |
| US9150644B2 (en) | 2011-04-12 | 2015-10-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Human monoclonal antibodies that bind insulin-like growth factor (IGF) I and II |
| UY34013A (es) | 2011-04-13 | 2012-11-30 | Astrazeneca Ab | ?compuestos de cromenona con actividad anti-tumoral?. |
| CA3019531A1 (en) | 2011-04-19 | 2012-10-26 | Pfizer Inc. | Combinations of anti-4-1bb antibodies and adcc-inducing antibodies for the treatment of cancer |
| EP2702173A1 (en) | 2011-04-25 | 2014-03-05 | OSI Pharmaceuticals, LLC | Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment |
| WO2012175991A1 (en) | 2011-06-24 | 2012-12-27 | Pharminox Limited | Fused pentacyclic anti - proliferative compounds |
| WO2013003697A1 (en) | 2011-06-30 | 2013-01-03 | Trustees Of Boston University | Method for controlling tumor growth, angiogenesis and metastasis using immunoglobulin containing and proline rich receptor-1 (igpr-1) |
| EP2731945A1 (en) | 2011-07-12 | 2014-05-21 | AstraZeneca AB | N- (6- ( (2r,3s) -3,4-dihydroxybutan-2-yloxy) -2- (4 - fluorobenzylthio) pyrimidin- 4 - yl) -3- methylazetidine- 1 - sulfonamide as chemokine receptor modulator |
| US9416132B2 (en) | 2011-07-21 | 2016-08-16 | Tolero Pharmaceuticals, Inc. | Substituted imidazo[1,2-b]pyridazines as protein kinase inhibitors |
| PT3009431T (pt) | 2011-07-27 | 2017-12-26 | Astrazeneca Ab | Compostos de 2-(2,4,5-anilino-substituídos)pirimidina como moduladores úteis do egfr para o tratamento do cancro |
| DE102011111400A1 (de) | 2011-08-23 | 2013-02-28 | Merck Patent Gmbh | Bicyclische heteroaromatische Verbindungen |
| ES2725790T3 (es) | 2011-08-26 | 2019-09-27 | Neupharma Inc | Algunas entidades químicas, composiciones, y métodos |
| CN104080335B (zh) | 2011-09-01 | 2017-06-09 | 钱向平 | 某些化学实体、组合物及方法 |
| WO2013040515A1 (en) | 2011-09-14 | 2013-03-21 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| WO2013043935A1 (en) | 2011-09-21 | 2013-03-28 | Neupharma, Inc. | Certain chemical entites, compositions, and methods |
| CN103814030A (zh) | 2011-09-22 | 2014-05-21 | 辉瑞大药厂 | 吡咯并嘧啶及嘌呤衍生物 |
| US20140235573A1 (en) | 2011-09-29 | 2014-08-21 | The University Of Liverpool | Prevention and/or treatment of cancer and/or cancer metastasis |
| US9249111B2 (en) | 2011-09-30 | 2016-02-02 | Neupharma, Inc. | Substituted quinoxalines as B-RAF kinase inhibitors |
| WO2013050725A1 (en) | 2011-10-04 | 2013-04-11 | King's College London | Ige anti -hmw-maa antibody |
| WO2013068902A1 (en) | 2011-11-08 | 2013-05-16 | Pfizer Inc. | Methods of treating inflammatory disorders using anti-m-csf antibodies |
| US20130178520A1 (en) | 2011-12-23 | 2013-07-11 | Duke University | Methods of treatment using arylcyclopropylamine compounds |
| WO2013112950A2 (en) | 2012-01-25 | 2013-08-01 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| SG11201404234YA (en) | 2012-01-28 | 2014-08-28 | Merck Patent Gmbh | Triazolo[4,5-d]pyrimidine derivatives |
| CA2863991C (en) | 2012-02-09 | 2020-08-11 | Merck Patent Gmbh | Tetrahydro-quinazolinone derivatives as tank and parp inhibitors |
| CN104093722B (zh) | 2012-02-09 | 2016-07-27 | 默克专利股份公司 | 作为TBK1和IKK抑制剂的呋喃并[3,2-b]-和噻吩并[3,2-b]吡啶衍生物 |
| EP2817313B1 (en) | 2012-02-21 | 2016-09-07 | Merck Patent GmbH | Furopyridine derivatives |
| WO2013124026A1 (en) | 2012-02-21 | 2013-08-29 | Merck Patent Gmbh | 8 - substituted 2 -amino - [1,2,4] triazolo [1, 5 -a] pyrazines as syk tryrosine kinase inhibitors and gcn2 serin kinase inhibitors |
| CN104254531B (zh) | 2012-02-21 | 2017-05-03 | 默克专利股份公司 | 环状二氨基嘧啶衍生物 |
| WO2013131609A1 (en) | 2012-03-07 | 2013-09-12 | Merck Patent Gmbh | Triazolopyrazine derivatives |
| WO2013143663A1 (en) | 2012-03-28 | 2013-10-03 | Merck Patent Gmbh | Bicyclic pyrazinone derivatives |
| WO2013144532A1 (en) | 2012-03-30 | 2013-10-03 | Astrazeneca Ab | 3 -cyano- 5 -arylamino-7 -cycloalkylaminopyrrolo [1, 5 -a] pyrimidine derivatives and their use as antitumor agents |
| PE20142422A1 (es) | 2012-04-05 | 2015-01-21 | Hoffmann La Roche | Anticuerpos biespecificos contra tweak humana e il 17 humana y usos de los mismos |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| WO2013165924A1 (en) | 2012-04-29 | 2013-11-07 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| SG11201406997WA (en) | 2012-05-04 | 2014-11-27 | Merck Patent Gmbh | Pyrrolotriazinone derivatives |
| SG11201408161RA (en) | 2012-06-08 | 2015-01-29 | Sutro Biopharma Inc | Antibodies comprising site-specific non-natural amino acid residues, methods of their preparation and methods of their use |
| GB201211021D0 (en) | 2012-06-21 | 2012-08-01 | Cancer Rec Tech Ltd | Pharmaceutically active compounds |
| EP3135690A1 (en) | 2012-06-26 | 2017-03-01 | Sutro Biopharma, Inc. | Modified fc proteins comprising site-specific non-natural amino acid residues, conjugates of the same, methods of their preparation and methods of their use |
| ES2673873T3 (es) | 2012-07-24 | 2018-06-26 | Merck Patent Gmbh | Derivados de hidroxiestatina para el tratamiento de la artrosis |
| US9725462B2 (en) | 2012-08-07 | 2017-08-08 | Merck Patent Gmbh | Pyridopyrimidine derivatives as protein kinase inhibitors |
| ES2773272T3 (es) | 2012-08-08 | 2020-07-10 | Merck Patent Gmbh | Derivados de (aza-)isoquinolinona |
| HK1209105A1 (en) | 2012-08-17 | 2016-03-24 | Cancer Therapeutics Crc Pty Limited | Vegfr3 inhibitors |
| EP2887965A1 (en) | 2012-08-22 | 2015-07-01 | ImmunoGen, Inc. | Cytotoxic benzodiazepine derivatives |
| ES2728864T3 (es) | 2012-08-31 | 2019-10-29 | Sutro Biopharma Inc | Aminoácidos modificados que comprenden un grupo azido |
| WO2014041349A1 (en) | 2012-09-12 | 2014-03-20 | Cancer Therapeutics Crc Pty Ltd | Tetrahydropyran-4-ylethylamino- or tetrahydropyranyl-4-ethyloxy-pyrimidines or -pyridazines as isoprenylcysteincarboxymethyl transferase inhibitors |
| EP2897618B1 (en) | 2012-09-24 | 2021-11-17 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| RU2650107C2 (ru) | 2012-09-26 | 2018-04-09 | Мерк Патент Гмбх | Производные хиназолинона в качестве ингибиторов parp |
| WO2014063205A1 (en) | 2012-10-26 | 2014-05-01 | The University Of Queensland | Use of endocytosis inhibitors and antibodies for cancer therapy |
| WO2014066955A1 (en) | 2012-11-05 | 2014-05-08 | Lindley Robyn Alice | Methods for determining the cause of somatic mutagenesis |
| EP2916838B1 (en) | 2012-11-12 | 2019-03-13 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| KR20150085045A (ko) | 2012-11-16 | 2015-07-22 | 메르크 파텐트 게엠베하 | 3-아미노시클로펜탄 카르복사미드 유도체 |
| 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 |
| WO2014117274A1 (en) | 2013-01-31 | 2014-08-07 | Neomed Institute | Imidazopyridine compounds and uses thereof |
| WO2014127881A1 (de) | 2013-02-25 | 2014-08-28 | Merck Patent Gmbh | 2-amino-3,4-dihydrc-chinazolin derivate und ihre verwendung als cathepsin d inhibitoren |
| US9999680B2 (en) | 2013-02-28 | 2018-06-19 | Immunogen, Inc. | Conjugates comprising cell-binding agents and maytansinoids as cytotoxic agents |
| HK1219423A1 (zh) | 2013-02-28 | 2017-04-07 | Immunogen, Inc. | 包含细胞结合剂及细胞毒素剂的轭合物 |
| WO2014135245A1 (en) | 2013-03-05 | 2014-09-12 | Merck Patent Gmbh | 9-(aryl or heteroaryl)-2-(pyrazolyl, pyrrolidinyl or cyclopentyl)aminopurine derivatives as anticancer agents |
| DK2970205T3 (da) | 2013-03-14 | 2019-07-29 | Tolero Pharmaceuticals Inc | JAK2- og ALK2-inhibitorer og fremgangsmåder til anvendelse deraf |
| CN113398147A (zh) | 2013-03-15 | 2021-09-17 | 纽罗森特里亚股份有限公司 | 用于癌症的镁组合物及其用途 |
| WO2014161570A1 (en) | 2013-04-03 | 2014-10-09 | Roche Glycart Ag | Antibodies against human il17 and uses thereof |
| US9206188B2 (en) | 2013-04-18 | 2015-12-08 | Arrien Pharmaceuticals Llc | Substituted pyrrolo[2,3-b]pyridines as ITK and JAK inhibitors |
| WO2014194030A2 (en) | 2013-05-31 | 2014-12-04 | Immunogen, Inc. | Conjugates comprising cell-binding agents and cytotoxic agents |
| EP3004073A1 (en) | 2013-06-07 | 2016-04-13 | Université catholique de Louvain | 3-carboxy substituted coumarin derivatives with a potential utility for the treatment of cancer diseases |
| CA2916533C (en) | 2013-06-25 | 2022-12-20 | University Of Canberra | Methods and compositions for modulating cancer stem cells |
| ES2658039T3 (es) | 2013-07-10 | 2018-03-08 | Sutro Biopharma, Inc. | Anticuerpos que comprenden múltiples residuos de aminoácidos no naturales sitio-específicos, métodos para su preparación y métodos de uso |
| AU2014308616B2 (en) | 2013-08-23 | 2018-12-06 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| JP6998657B2 (ja) | 2013-09-18 | 2022-02-04 | エピアクシス セラピューティクス プロプライエタリー リミテッド | 幹細胞調節ii |
| WO2015048852A1 (en) | 2013-10-01 | 2015-04-09 | The University Of Queensland | Kits and methods for diagnosis, screening, treatment and disease monitoring |
| WO2015051302A1 (en) | 2013-10-04 | 2015-04-09 | Aptose Biosciences Inc. | Compositions and methods for treating cancers |
| EP3055298B1 (en) | 2013-10-11 | 2020-04-29 | Sutro Biopharma, Inc. | Modified amino acids comprising tetrazine functional groups, methods of preparation, and methods of their use |
| UA115388C2 (uk) | 2013-11-21 | 2017-10-25 | Пфайзер Інк. | 2,6-заміщені пуринові похідні та їх застосування в лікуванні проліферативних захворювань |
| GB201321146D0 (en) * | 2013-11-29 | 2014-01-15 | Cancer Rec Tech Ltd | Quinazoline compounds |
| US8980273B1 (en) | 2014-07-15 | 2015-03-17 | Kymab Limited | Method of treating atopic dermatitis or asthma using antibody to IL4RA |
| US8986691B1 (en) | 2014-07-15 | 2015-03-24 | Kymab Limited | Method of treating atopic dermatitis or asthma using antibody to IL4RA |
| 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 |
| CN104829542B (zh) * | 2014-02-10 | 2018-02-02 | 中国科学院上海药物研究所 | 苯胺嘧啶类化合物、其制备方法和医药用途 |
| GB201403536D0 (en) | 2014-02-28 | 2014-04-16 | Cancer Rec Tech Ltd | Inhibitor compounds |
| PT3126521T (pt) | 2014-04-04 | 2019-06-27 | Crown Bioscience Inc Taicang | Gene de fusão hnf4g-rspo2 |
| WO2015155624A1 (en) | 2014-04-10 | 2015-10-15 | Pfizer Inc. | Dihydropyrrolopyrimidine derivatives |
| MX2016014143A (es) | 2014-04-30 | 2017-02-15 | Pfizer | Derivados de diheterociclo enlazado a cicloalquilo. |
| WO2016001789A1 (en) | 2014-06-30 | 2016-01-07 | Pfizer Inc. | Pyrimidine derivatives as pi3k inhibitors for use in the treatment of cancer |
| EP3473271B1 (en) | 2014-07-31 | 2022-07-20 | The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services | Human monoclonal antibodies against epha4 and their use |
| CN105330653A (zh) | 2014-08-11 | 2016-02-17 | 石药集团中奇制药技术(石家庄)有限公司 | 喹唑啉衍生物 |
| EP3185858A4 (en) | 2014-08-25 | 2017-12-27 | University of Canberra | Compositions for modulating cancer stem cells and uses therefor |
| US20190072557A1 (en) | 2014-11-17 | 2019-03-07 | The University Of Queensland | Glycoprotein biomarkers for esophageal adenocarcinoma and barrett's esophagus and uses thereof |
| WO2016097918A1 (en) | 2014-12-18 | 2016-06-23 | Pfizer Inc. | Pyrimidine and triazine derivatives and their use as axl inhibitors |
| MA41179A (fr) | 2014-12-19 | 2017-10-24 | Cancer Research Tech Ltd | Composés inhibiteurs de parg |
| GB201501870D0 (en) | 2015-02-04 | 2015-03-18 | Cancer Rec Tech Ltd | Autotaxin inhibitors |
| GB201502020D0 (en) | 2015-02-06 | 2015-03-25 | Cancer Rec Tech Ltd | Autotaxin inhibitory compounds |
| US10947201B2 (en) | 2015-02-17 | 2021-03-16 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| JP6851978B2 (ja) | 2015-04-20 | 2021-03-31 | スミトモ ダイニッポン ファーマ オンコロジー, インコーポレイテッド | ミトコンドリアプロファイリングによるアルボシジブ応答の予測 |
| US10011629B2 (en) | 2015-05-01 | 2018-07-03 | Cocrystal Pharma, Inc. | Nucleoside analogs for treatment of the flaviviridae family of viruses and cancer |
| JP6510075B2 (ja) | 2015-05-18 | 2019-05-08 | トレロ ファーマシューティカルズ, インコーポレイテッド | バイオアベイラビリティが高いアルボシジブプロドラッグ |
| GB201510019D0 (en) | 2015-06-09 | 2015-07-22 | Cancer Therapeutics Crc Pty Ltd | Compounds |
| WO2017009751A1 (en) | 2015-07-15 | 2017-01-19 | Pfizer Inc. | Pyrimidine derivatives |
| EP3331510A4 (en) | 2015-08-03 | 2019-04-03 | Tolero Pharmaceuticals, Inc. | COMBINATION THERAPIES FOR THE TREATMENT OF CANCER |
| USRE49850E1 (en) | 2015-08-04 | 2024-02-27 | Aucentra Therapeutics Pty Ltd | N-(pyridin-2-yl)-4-(thiazol-5-yl)pyrimidin-2-amine derivatives as therapeutic compounds |
| JP6850294B2 (ja) | 2015-08-26 | 2021-03-31 | ジーエムディーエックス カンパニー プロプライエタリー リミテッド | 癌の再発を検出する方法 |
| GB201516504D0 (en) | 2015-09-17 | 2015-11-04 | Astrazeneca Ab | Imadazo(4,5-c)quinolin-2-one Compounds and their use in treating cancer |
| GB201519568D0 (en) | 2015-11-05 | 2015-12-23 | Astrazeneca Ab | Imidazo[4,5-c]quinolin-2-one compounds and their use in treating cancer |
| US20180371551A1 (en) | 2015-12-03 | 2018-12-27 | Agios Pharmaceuticals, Inc. | Mat2a inhibitors for treating mtap null cancer |
| JP7412079B2 (ja) | 2015-12-23 | 2024-01-12 | レプルカ プロプライアタリー リミティド | 核酸オリゴマーとその用途 |
| US11708413B2 (en) | 2016-01-27 | 2023-07-25 | Sutro Biopharma, Inc. | Anti-CD74 antibody conjugates, compositions comprising anti-CD74 antibody conjugates and methods of using anti-CD74 antibody conjugates |
| CN116082457A (zh) | 2016-02-01 | 2023-05-09 | 堪培拉大学 | 蛋白化合物及其用途 |
| GB201604182D0 (en) | 2016-03-11 | 2016-04-27 | Astrazeneca Ab | Imidazo[4,5-c]quinolin-2-one compounds and their use in treating cancer |
| WO2017162605A1 (en) | 2016-03-21 | 2017-09-28 | Astrazeneca Ab | Cinnolin-4-amine compounds and their use in treating cancer |
| US20190119270A1 (en) | 2016-04-07 | 2019-04-25 | Astrazeneca Ab | N-Oxide Compound and Its Use in Treating Cancer |
| EP3442535B1 (en) | 2016-04-15 | 2022-06-01 | Cancer Research Technology Limited | Heterocyclic compounds as ret kinase inhibitors |
| GB2554333A (en) | 2016-04-26 | 2018-04-04 | Big Dna Ltd | Combination therapy |
| GB201608227D0 (en) | 2016-05-11 | 2016-06-22 | Astrazeneca Ab | Imidazo[4,5-c]quinolin-2-one compounds and their use in treating cancer |
| JP6985388B2 (ja) | 2016-07-29 | 2021-12-22 | ラプト・セラピューティクス・インコーポレイテッド | ケモカイン受容体調節剤及びそれの使用 |
| EP4006035B1 (en) | 2016-08-15 | 2023-11-22 | Neupharma, Inc. | Quinazoline derivatives as tyrosine kinase inhibitors for the treatment of cancer |
| EP3507305A1 (en) | 2016-09-02 | 2019-07-10 | Dana-Farber Cancer Institute, Inc. | Composition and methods of treating b cell disorders |
| CN110036006B (zh) | 2016-09-22 | 2022-12-13 | 癌症研究科技有限公司 | 嘧啶酮衍生物的制备和用途 |
| GB201617103D0 (en) | 2016-10-07 | 2016-11-23 | Cancer Research Technology Limited | Compound |
| US11279694B2 (en) | 2016-11-18 | 2022-03-22 | Sumitomo Dainippon Pharma Oncology, Inc. | Alvocidib prodrugs and their use as protein kinase inhibitors |
| US10786502B2 (en) | 2016-12-05 | 2020-09-29 | Apros Therapeutics, Inc. | Substituted pyrimidines containing acidic groups as TLR7 modulators |
| EP3548478B1 (en) | 2016-12-05 | 2021-11-17 | Apros Therapeutics, Inc. | Pyrimidine compounds containing acidic groups |
| CA3047557A1 (en) | 2016-12-19 | 2018-06-28 | Tolero Pharmaceuticals, Inc. | Profiling peptides and methods for sensitivity profiling |
| HUE054548T2 (hu) | 2016-12-20 | 2021-09-28 | Astrazeneca Ab | Amino-triazolopiridin vegyületek és azok alkalmazása rák kezelésében |
| WO2018141002A2 (en) | 2017-02-01 | 2018-08-09 | University Of South Australia | DERIVATIVES OF N-CYCLOALKYL/HETEROCYCLOALKYL-4-(IMIDAZO [1,2-a]PYRIDINE)PYRIMIDIN-2-AMINE AS THERAPEUTIC AGENTS |
| EP3592730B1 (en) | 2017-03-09 | 2021-08-04 | Truly Translational Sweden AB | Prodrugs of sulfasalazine, pharmaceutical compositions thereof and their use in the treatment of autoimmune disease |
| JOP20190209A1 (ar) | 2017-03-16 | 2019-09-12 | Astrazeneca Ab | مركبات إيميدازو [ 4، 5-c ] كينولين-2-أون ديوترومية واستخدامها في علاج السرطان |
| GB201704325D0 (en) | 2017-03-17 | 2017-05-03 | Argonaut Therapeutics Ltd | Compounds |
| GB201705971D0 (en) | 2017-04-13 | 2017-05-31 | Cancer Res Tech Ltd | Inhibitor compounds |
| CN108864079B (zh) | 2017-05-15 | 2021-04-09 | 深圳福沃药业有限公司 | 一种三嗪化合物及其药学上可接受的盐 |
| CN111163839B (zh) | 2017-05-26 | 2024-05-28 | 癌症研究科技有限公司 | 苯并咪唑酮衍生的bcl6抑制剂 |
| ES2975661T3 (es) | 2017-05-26 | 2024-07-11 | Cancer Research Tech Ltd | Inhibidores de BCL6 derivados de la 2-quinolona |
| PL3630188T3 (pl) | 2017-05-31 | 2022-01-03 | Amplio Pharma Ab | Kompozycja farmaceutyczna zawierająca kombinację metotreksatu i nowobiocyny oraz zastosowanie wspomnianej kompozycji w terapii |
| US11319304B2 (en) * | 2017-06-28 | 2022-05-03 | Vanderbilt University | Pyridine quinoline compounds as MGLUR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction |
| EP3648797A1 (en) | 2017-07-05 | 2020-05-13 | EPOS-Iasis Research and Development, Ltd | Multifunctional conjugates |
| EP3658588A1 (en) | 2017-07-26 | 2020-06-03 | Sutro Biopharma, Inc. | Methods of using anti-cd74 antibodies and antibody conjugates in treatment of t-cell lymphoma |
| EP3661941B1 (en) | 2017-08-01 | 2022-12-14 | Merck Patent GmbH | Thiazolopyridine derivatives as adenosine receptor antagonists |
| CN111278840B (zh) | 2017-08-18 | 2023-11-17 | 癌症研究科技有限公司 | 吡咯并[2,3-b]吡啶化合物及其治疗癌症的用途 |
| US11192899B2 (en) | 2017-08-21 | 2021-12-07 | Merck Patent Gmbh | Quinoxaline derivatives as adenosine receptor antagonists |
| CN110997662B (zh) | 2017-08-21 | 2023-10-31 | 默克专利股份公司 | 作为腺苷受体拮抗剂的苯并咪唑衍生物 |
| 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 |
| SG11202002310UA (en) | 2017-09-18 | 2020-04-29 | Sutro Biopharma Inc | Anti- folate receptor alpha antibody conjugates and their uses |
| WO2019057757A1 (en) | 2017-09-20 | 2019-03-28 | Astrazeneca Ab | 1,3-DIHYDROIMIDAZO [4,5-C] CINNOLIN-2-ONE COMPOUNDS AND THEIR USE IN THE TREATMENT OF CANCER |
| TWI702205B (zh) | 2017-10-06 | 2020-08-21 | 俄羅斯聯邦商拜奧卡德聯合股份公司 | 表皮生長因子受體抑制劑 |
| WO2019075367A1 (en) | 2017-10-13 | 2019-04-18 | Tolero Pharmaceuticals, Inc. | PKM2 ACTIVATORS IN COMBINATION WITH OXYGEN REACTIVE SPECIES FOR THE TREATMENT OF CANCER |
| WO2019090272A1 (en) | 2017-11-06 | 2019-05-09 | Flx Bio, Inc. | Chemokine receptor modulators for treatment of epstein barr virus positive cancer |
| EP3489222A1 (en) | 2017-11-23 | 2019-05-29 | medac Gesellschaft für klinische Spezialpräparate mbH | Sulfasalazine salts, production processes and uses |
| DK3488868T3 (da) | 2017-11-23 | 2023-11-27 | Medac Ges Fuer Klinische Spezialpraeparate Mbh | Farmaceutisk sammensætning til oral indgivelse, som indeholder sulfasalazin og/eller et organisk sulfasalazinsalt, fremstillingsfremgangsmåde samt anvendelse |
| EP3740484B1 (en) | 2018-01-15 | 2024-09-11 | Aucentra Therapeutics Pty Ltd | 5-(pyrimidin-4-yl)thiazol-2-yl urea derivatives as therapeutic agents |
| GB201801128D0 (en) | 2018-01-24 | 2018-03-07 | Univ Oxford Innovation Ltd | Compounds |
| KR102860287B1 (ko) | 2018-01-26 | 2025-09-16 | 랩트 테라퓨틱스, 인크. | 케모카인 수용체 조정제 및 그의 용도 |
| US11465975B2 (en) | 2018-02-08 | 2022-10-11 | Neupharma, Inc | Certain chemical entities, compositions, and methods |
| WO2019175093A1 (en) | 2018-03-12 | 2019-09-19 | Astrazeneca Ab | Method for treating lung cancer |
| JP7493454B2 (ja) | 2018-04-13 | 2024-05-31 | キャンサー・リサーチ・テクノロジー・リミテッド | Bcl6阻害剤 |
| CN112423747A (zh) | 2018-04-27 | 2021-02-26 | 云杉生物科学公司 | 用于治疗睾丸肾上腺残余瘤和卵巢肾上腺残余瘤的方法 |
| AR114910A1 (es) | 2018-06-04 | 2020-10-28 | Apros Therapeutics Inc | Compuestos de pirimidina que contienen grupos ácidos |
| GB201809102D0 (en) | 2018-06-04 | 2018-07-18 | Univ Oxford Innovation Ltd | Compounds |
| WO2019236631A1 (en) | 2018-06-05 | 2019-12-12 | Rapt Therapeutics, Inc. | Pyrazolo-pyrimidin-amino-cycloalkyl compounds and their therapeutic uses |
| GB201810092D0 (en) | 2018-06-20 | 2018-08-08 | Ctxt Pty Ltd | Compounds |
| GB201810581D0 (en) | 2018-06-28 | 2018-08-15 | Ctxt Pty Ltd | Compounds |
| 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 |
| CN115636833B (zh) | 2018-09-14 | 2024-11-29 | 苏州赞荣医药科技有限公司 | 作为ATM激酶选择性调节剂的取代的咪唑并[4,5-c]噌啉-2-酮化合物及其用途 |
| US20220047716A1 (en) | 2018-09-17 | 2022-02-17 | Sutro Biopharma, Inc. | Combination therapies with anti-folate receptor antibody conjugates |
| ES3007082T3 (en) | 2018-09-18 | 2025-03-19 | Hoffmann La Roche | Quinazoline derivatives as antitumor agents |
| US11084829B2 (en) | 2018-09-24 | 2021-08-10 | Rapt Therapeutics, Inc. | Ubiquitin-specific-processing protease 7 (USP7) modulators and uses thereof |
| BR112021007435A2 (pt) | 2018-10-25 | 2021-08-03 | Merck Patent Gmbh | derivados de 5-azaindazol como antagonistas de receptor de adenosina |
| WO2020083856A1 (en) | 2018-10-25 | 2020-04-30 | Merck Patent Gmbh | 5-azaindazole derivatives as adenosine receptor antagonists |
| GB201819126D0 (en) | 2018-11-23 | 2019-01-09 | Cancer Research Tech Ltd | Inhibitor compounds |
| US11034710B2 (en) | 2018-12-04 | 2021-06-15 | Sumitomo Dainippon Pharma Oncology, Inc. | CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer |
| ES3031988T3 (en) | 2018-12-25 | 2025-07-14 | Beijing Baishihekang Pharmaceutical Tech Bsjpharma Co Ltd | Small rna medicament for prevention and treatment of inflammation-related diseases and combination thereof |
| AR117844A1 (es) | 2019-01-22 | 2021-09-01 | Merck Patent Gmbh | Derivados de tiazolopiridina como antagonistas del receptor de adenosina |
| CA3127502A1 (en) | 2019-02-12 | 2020-08-20 | Sumitomo Dainippon Pharma Oncology, Inc. | Formulations comprising heterocyclic protein kinase inhibitors |
| CN113727716A (zh) | 2019-02-25 | 2021-11-30 | 贝卢斯医疗咳嗽病公司 | 采用p2x3调节剂的治疗 |
| US11033547B2 (en) | 2019-03-07 | 2021-06-15 | Merck Patent Gmbh | Carboxamide-pyrimidine derivatives as SHP2 antagonists |
| US11793802B2 (en) | 2019-03-20 | 2023-10-24 | Sumitomo Pharma Oncology, Inc. | Treatment of acute myeloid leukemia (AML) with venetoclax failure |
| WO2020198077A1 (en) | 2019-03-22 | 2020-10-01 | Sumitomo Dainippon Pharma Oncology, Inc. | Compositions comprising pkm2 modulators and methods of treatment using the same |
| SG11202109438TA (en) | 2019-03-28 | 2021-10-28 | Amplia Therapeutics Ltd | A salt and crystal form of a fak inhibitor |
| MX2021011810A (es) | 2019-03-29 | 2021-10-26 | Astrazeneca Ab | Osimertinib para su uso en el tratamiento de cancer de pulmon de celulas no peque?as. |
| CN111747931A (zh) | 2019-03-29 | 2020-10-09 | 深圳福沃药业有限公司 | 用于治疗癌症的氮杂芳环酰胺衍生物 |
| JP7762957B2 (ja) | 2019-04-05 | 2025-10-31 | ストーム・セラピューティクス・リミテッド | Mettl3阻害化合物 |
| US11001561B2 (en) | 2019-04-08 | 2021-05-11 | Merck Patent Gmbh | Pyrimidinone derivatives as SHP2 antagonists |
| GB201905328D0 (en) | 2019-04-15 | 2019-05-29 | Azeria Therapeutics Ltd | Inhibitor compounds |
| US20220362394A1 (en) | 2019-05-03 | 2022-11-17 | Sutro Biopharma, Inc. | Anti-bcma antibody conjugates |
| GB201908885D0 (en) | 2019-06-20 | 2019-08-07 | Storm Therapeutics Ltd | Therapeutic compounds |
| AU2020335054A1 (en) | 2019-08-31 | 2022-03-24 | Etern Biopharma (Shanghai) Co., Ltd. | Pyrazole derivative for FGFR inhibitor and preparation method therefor |
| WO2021055744A1 (en) | 2019-09-20 | 2021-03-25 | Ideaya Biosciences, Inc. | 4-substituted indole and indazole sulfonamido derivatives as parg inhibitors |
| GB201913988D0 (en) | 2019-09-27 | 2019-11-13 | Celleron Therapeutics Ltd | Novel treatment |
| GB201914860D0 (en) | 2019-10-14 | 2019-11-27 | Cancer Research Tech Ltd | Inhibitor compounds |
| GB201915831D0 (en) | 2019-10-31 | 2019-12-18 | Cancer Research Tech Ltd | Compounds, compositions and therapeutic uses thereof |
| GB201915828D0 (en) | 2019-10-31 | 2019-12-18 | Cancer Research Tech Ltd | Compounds, compositions and therapeutic uses thereof |
| GB201915829D0 (en) | 2019-10-31 | 2019-12-18 | Cancer Research Tech Ltd | Compounds, compositions and therapeutic uses thereof |
| AU2020394867A1 (en) | 2019-12-02 | 2022-05-26 | Storm Therapeutics Limited | Polyheterocyclic compounds as METTL3 inhibitors |
| WO2021155006A1 (en) | 2020-01-31 | 2021-08-05 | Les Laboratoires Servier Sas | Inhibitors of cyclin-dependent kinases and uses thereof |
| EP4114852A1 (en) | 2020-03-03 | 2023-01-11 | Sutro Biopharma, Inc. | Antibodies comprising site-specific glutamine tags, methods of their preparation and methods of their use |
| GB202004960D0 (en) | 2020-04-03 | 2020-05-20 | Kinsenus Ltd | Inhibitor compounds |
| GB202012969D0 (en) | 2020-08-19 | 2020-09-30 | Univ Of Oxford | Inhibitor compounds |
| WO2022074379A1 (en) | 2020-10-06 | 2022-04-14 | Storm Therapeutics Limited | Mettl3 inhibitory compounds |
| WO2022074391A1 (en) | 2020-10-08 | 2022-04-14 | Storm Therapeutics Limited | Compounds inhibitors of mettl3 |
| EP3992191A1 (en) | 2020-11-03 | 2022-05-04 | Deutsches Krebsforschungszentrum | Imidazo[4,5-c]quinoline compounds and their use as atm kinase inhibitors |
| GB202102895D0 (en) | 2021-03-01 | 2021-04-14 | Cambridge Entpr Ltd | Novel compounds, compositions and therapeutic uses thereof |
| WO2022197641A1 (en) | 2021-03-15 | 2022-09-22 | Rapt Therapeutics, Inc. | 1h-pyrazolo[3,4-d]pyrimidin-6-yl-amine derivatives as hematopoietic progenitor kinase 1 (hpk1) modulators and/or inhibitors for the treatment of cancer and other diseases |
| US11931420B2 (en) | 2021-04-30 | 2024-03-19 | Celgene Corporation | Combination therapies using an anti-BCMA antibody drug conjugate (ADC) in combination with a gamma secretase inhibitor (GSI) |
| AU2022270880A1 (en) | 2021-05-03 | 2023-09-28 | Merck Patent Gmbh | Her2 targeting fc antigen binding fragment-drug conjugates |
| BR112023024040A2 (pt) | 2021-05-17 | 2024-02-06 | Hk Inno N Corp | Composto, o isômero óptico do mesmo, o solvato do mesmo, o hidrato do mesmo ou o sal farmaceuticamente aceitável do mesmo e seu uso, composição farmacêutica que compreende o dito composto, composição de alimento funcional para a saúde e preparação combinada |
| AU2022280341A1 (en) | 2021-05-25 | 2024-01-04 | Merck Patent Gmbh | Egfr targeting fc antigen binding fragment-drug conjugates |
| GB202107907D0 (en) | 2021-06-02 | 2021-07-14 | Storm Therapeutics Ltd | Combination therapies |
| GB202108383D0 (en) | 2021-06-11 | 2021-07-28 | Argonaut Therapeutics Ltd | Compounds useful in the treatment or prevention of a prmt5-mediated disorder |
| US20250002491A1 (en) | 2021-10-04 | 2025-01-02 | Forx Therapeutics Ag | N,n-dimethyl-4-(7-(n-(1-methylcyclopropyl)sulfamoyl)-imidazo[1,5-a]pyridin-5-yl)piperazine-1-carboxamide derivatives and the corresponding pyrazolo[1,5-a]pyridine derivatives as parg inhibitors for the treatment of cancer |
| WO2023057389A1 (en) | 2021-10-04 | 2023-04-13 | Forx Therapeutics Ag | Parg inhibitory compounds |
| JP2024539212A (ja) | 2021-10-20 | 2024-10-28 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | キナゾリン誘導体の結晶形態、調製、組成物およびその使用 |
| CN119421877A (zh) | 2022-01-10 | 2025-02-11 | 默克专利股份公司 | 作为hset抑制剂的取代杂环化合物 |
| GB202202199D0 (en) | 2022-02-18 | 2022-04-06 | Cancer Research Tech Ltd | Compounds |
| WO2023175185A1 (en) | 2022-03-17 | 2023-09-21 | Forx Therapeutics Ag | 2,4-dioxo-1,4-dihydroquinazoline derivatives as parg inhibitors for the treatment of cancer |
| WO2023175184A1 (en) | 2022-03-17 | 2023-09-21 | Forx Therapeutics Ag | 2,4-dioxo-1,4-dihydroquinazoline derivatives as parg inhibitors for the treatment of cancer |
| WO2023186881A1 (en) | 2022-03-29 | 2023-10-05 | Baden-Württemberg Stiftung Ggmbh | P38 map kinase inhibitors for use in the treatment of colorectal cancer |
| GB202204935D0 (en) | 2022-04-04 | 2022-05-18 | Cambridge Entpr Ltd | Nanoparticles |
| WO2023196432A1 (en) | 2022-04-06 | 2023-10-12 | Rapt Therapeutics, Inc. | Chemokine receptor modulators and uses thereof |
| GB202209404D0 (en) | 2022-06-27 | 2022-08-10 | Univ Of Sussex | Compounds |
| CN120076831A (zh) | 2022-06-30 | 2025-05-30 | 苏特罗生物制药公司 | 抗ror1抗体和抗体缀合物、包含抗ror1抗体或抗体缀合物的组合物、以及制备和使用抗ror1抗体和抗体缀合物的方法 |
| EP4565592A1 (en) | 2022-08-01 | 2025-06-11 | Neupharma, Inc. | Crystalline salts of crystalline salts of (3s,5r,8r,9s,10s,13r,14s,17r)-14-hydroxy-10,13-dimethyl-17-(2- oxo-2h-pyran-5-yl)hexadecahydro-1h-cyclopenta[a]phenanthren-3-yl piperazine-1-carboxylate |
| GB202213167D0 (en) | 2022-09-08 | 2022-10-26 | Cambridge Entpr Ltd | Novel compounds, compositions and therapeutic uses thereof |
| GB202213164D0 (en) | 2022-09-08 | 2022-10-26 | Cambridge Entpr Ltd | Novel compounds, compositions and therapeutic uses thereof |
| GB202213162D0 (en) | 2022-09-08 | 2022-10-26 | Cambridge Entpr Ltd | Prodrugs |
| GB202213163D0 (en) | 2022-09-08 | 2022-10-26 | Cambridge Entpr Ltd | Novel compounds, compositions and therapeutic uses thereof |
| GB202213166D0 (en) | 2022-09-08 | 2022-10-26 | Cambridge Entpr Ltd | Novel compounds, compositions and therapeutic uses thereof |
| WO2024074497A1 (en) | 2022-10-03 | 2024-04-11 | Forx Therapeutics Ag | Parg inhibitory compound |
| WO2024094962A1 (en) | 2022-11-02 | 2024-05-10 | Cancer Research Technology Limited | Pyrido[2,3-d]pyrimidin-2-amine derivatives as egfr inhibitors for the treatment of cancer |
| WO2024094963A1 (en) | 2022-11-02 | 2024-05-10 | Cancer Research Technology Limited | 2-amino-pyrido[2,3-d]pyrimidin-7(8h)-one and 7-amino-1-pyrimido[4,5-d]pyrimidin-2(1 h)-one derivatives as egfr inhibitors for the treatment of cancer |
| AU2023375996A1 (en) | 2022-11-07 | 2025-06-19 | Merck Patent Gmbh | Substituted bi-and tricyclic hset inhibitors |
| GB202218672D0 (en) | 2022-12-12 | 2023-01-25 | Storm Therapeutics Ltd | Inhibitory compounds |
| EP4423089A4 (en) | 2023-01-18 | 2025-01-08 | Antengene Discovery Limited | PRMT5 INHIBITOR COMPOUNDS AND THEIR USES |
| WO2024173524A1 (en) | 2023-02-14 | 2024-08-22 | Ideaya Biosciences, Inc. | Heteroaryl-substituted benzimidazole compounds |
| WO2024173453A1 (en) | 2023-02-14 | 2024-08-22 | Ideaya Biosciences, Inc. | Heteroaryl-substituted imidazopyridine compounds |
| WO2024173530A1 (en) | 2023-02-14 | 2024-08-22 | Ideaya Biosciences, Inc. | Heteroaryl-substituted pyrazolo/imidazo pyridine compounds |
| WO2024173514A1 (en) | 2023-02-14 | 2024-08-22 | Ideaya Biosciences, Inc. | Amide and ester-substituted imidazopyridine compounds |
| US12162895B2 (en) | 2023-03-10 | 2024-12-10 | Breakpoint Therapeutics Gmbh | DNA polymerase theta inhibitor for treatment of cancer |
| EP4434972A1 (en) | 2023-03-22 | 2024-09-25 | Eberhard-Karls-Universität Tübingen | Atm kinase inhibitors |
| WO2024209035A1 (en) | 2023-04-05 | 2024-10-10 | Forx Therapeutics Ag | Parg inhibitory compounds |
| GB2631509A (en) | 2023-07-04 | 2025-01-08 | Univ Liverpool | Compositions |
| GB2631507A (en) | 2023-07-04 | 2025-01-08 | Univ Liverpool | Compositions |
| WO2025043017A1 (en) * | 2023-08-21 | 2025-02-27 | University Of Central Florida Research Foundation, Inc. | Efficient identification of new small molecules targeting succinate dehydrogenase |
| WO2025046148A1 (en) | 2023-09-01 | 2025-03-06 | Forx Therapeutics Ag | Novel parg inhibitors |
| WO2025056923A1 (en) | 2023-09-15 | 2025-03-20 | Cambridge Enterprise Limited | Combination therapy |
| WO2025073792A1 (en) | 2023-10-02 | 2025-04-10 | Forx Therapeutics Ag | Wrn inhibitory compounds |
| WO2025073870A1 (en) | 2023-10-03 | 2025-04-10 | Forx Therapeutics Ag | Parg inhibitory compound |
| GB202315149D0 (en) | 2023-10-03 | 2023-11-15 | Celleron Therapeutics Ltd | Combination therapy |
| WO2025081117A2 (en) | 2023-10-13 | 2025-04-17 | Sutro Biopharma, Inc. | Anti-tissue factor antibodies and antibody conjugates, compositions comprising anti-tissue factor antibodies or antibody conjugates, and methods of making and using anti-tissue factor antibodies and antibody conjugates |
| GB202316595D0 (en) | 2023-10-30 | 2023-12-13 | Storm Therapeutics Ltd | Inhibitory compounds |
| GB202316683D0 (en) | 2023-10-31 | 2023-12-13 | Storm Therapeutics Ltd | Inhibitory compounds |
| WO2025093755A1 (en) | 2023-11-01 | 2025-05-08 | Forx Therapeutics Ag | Novel parc inhibitors |
| GB202317368D0 (en) | 2023-11-13 | 2023-12-27 | Breakpoint Therapeutics Gmbh | Novel compounds, compositions and therapeutic uses thereof |
| WO2025104443A1 (en) | 2023-11-14 | 2025-05-22 | Storm Therapeutics Ltd | Inhibitory compounds |
| WO2025114480A1 (en) | 2023-11-28 | 2025-06-05 | Forx Therapeutics Ag | Wrn inhibitory compounds |
| WO2025136811A1 (en) | 2023-12-18 | 2025-06-26 | Ideaya Biosciences, Inc. | Chemical compounds and uses thereof |
| GB202319863D0 (en) | 2023-12-21 | 2024-02-07 | Breakpoint Therapeutics Gmbh | Movel compounds, compositions and therapeutics uses thereof |
| GB202319864D0 (en) | 2023-12-21 | 2024-02-07 | Breakpoint Therapeutics Gmbh | Novel compounds, compositions and therapeutic uses thereof |
| WO2025133396A1 (en) | 2023-12-22 | 2025-06-26 | Forx Therapeutics Ag | Novel bicyclo heteroaryl parg inhibitors |
| WO2025133395A1 (en) | 2023-12-22 | 2025-06-26 | Forx Therapeutics Ag | Bicyclic (hetero)arylene wrn inhibitory compounds |
| WO2025191176A1 (en) | 2024-03-14 | 2025-09-18 | Forx Therapeutics Ag | Wrn inhibitory compounds |
| NL2037411B1 (en) | 2024-04-08 | 2025-10-31 | Univ Leiden | Protac compounds |
| WO2025250825A1 (en) | 2024-05-30 | 2025-12-04 | Sutro Biopharma, Inc. | Anti-trop2 antibodies, compositions comprising anti-trop2 antibodies and methods of making and using anti-trop2 antibodies |
| GB202407738D0 (en) | 2024-05-31 | 2024-07-17 | Storm Therapeutics Ltd | Inhibitory compounds |
| CN119912427A (zh) * | 2025-01-02 | 2025-05-02 | 浙江工业大学 | 2-溴-4-(哌啶基甲基)吡啶的合成方法 |
Family Cites Families (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3266990A (en) * | 1963-09-24 | 1966-08-16 | Warner Lambert Pharmaceutical | Derivatives of quinazoline |
| JPS5538325A (en) * | 1978-09-11 | 1980-03-17 | Sankyo Co Ltd | 4-anilinoquinazoline derivative and its preparation |
| US4343940A (en) * | 1979-02-13 | 1982-08-10 | Mead Johnson & Company | Anti-tumor quinazoline compounds |
| GB2160201B (en) * | 1984-06-14 | 1988-05-11 | Wyeth John & Brother Ltd | Quinazoline and cinnoline derivatives |
| DE68917485T2 (de) * | 1988-01-23 | 1995-02-09 | Kyowa Hakko Kogyo Kk | Pyridazinon-Derivate und diese enthaltende pharmazeutische Zubereitungen. |
| IL89029A (en) * | 1988-01-29 | 1993-01-31 | Lilly Co Eli | Fungicidal quinoline and cinnoline derivatives, compositions containing them, and fungicidal methods of using them |
| US5411963A (en) * | 1988-01-29 | 1995-05-02 | Dowelanco | Quinazoline derivatives |
| ES2071484T3 (es) * | 1991-02-20 | 1995-06-16 | Pfizer | Derivados de 2,4-diaminoquinazolinas para aumentar la actividad antitumoral. |
| DE4105518A1 (de) | 1991-02-22 | 1992-08-27 | Basf Ag | Sulfonylharnstoffderivate, verfahren zu ihrer herstellung und ihre verwendung |
| AU658646B2 (en) * | 1991-05-10 | 1995-04-27 | Rhone-Poulenc Rorer International (Holdings) 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 |
| US5721237A (en) * | 1991-05-10 | 1998-02-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Protein tyrosine kinase aryl and heteroaryl quinazoline compounds having selective inhibition of HER-2 autophosphorylation properties |
| NZ243082A (en) * | 1991-06-28 | 1995-02-24 | Ici Plc | 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof |
| GB9300059D0 (en) * | 1992-01-20 | 1993-03-03 | Zeneca Ltd | Quinazoline derivatives |
| DE4208254A1 (de) * | 1992-03-14 | 1993-09-16 | Hoechst Ag | Substituierte pyrimidine, verfahren zu ihrer herstellung und ihre verwendung als schaedlingsbekaempfungsmittel und fungizid |
| US5270466A (en) * | 1992-06-11 | 1993-12-14 | American Cyanamid Company | Substituted quinazoline fungicidal agents |
| US6177401B1 (en) * | 1992-11-13 | 2001-01-23 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften | Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis |
| GB9323290D0 (en) * | 1992-12-10 | 1994-01-05 | Zeneca Ltd | Quinazoline derivatives |
| DE4309613C2 (de) | 1993-03-24 | 1996-10-17 | Bfi Entsorgungstech | Vorrichtung zum Verteilen fester Abfallmaterialien auf einem Transportband |
| GB9314884D0 (en) * | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Tricyclic derivatives |
| GB9314893D0 (en) * | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Quinazoline derivatives |
| WO1995006648A1 (fr) * | 1993-09-03 | 1995-03-09 | Kyowa Hakko Kogyo Co., Ltd. | Derive d'imidazoquinazoline |
| GB9325217D0 (en) * | 1993-12-09 | 1994-02-09 | Zeneca Ltd | Pyrimidine derivatives |
| US5700823A (en) * | 1994-01-07 | 1997-12-23 | Sugen, Inc. | Treatment of platelet derived growth factor related disorders such as cancers |
| 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 |
| IL112248A0 (en) * | 1994-01-25 | 1995-03-30 | Warner Lambert Co | Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them |
| JP2890267B2 (ja) * | 1994-02-23 | 1999-05-10 | ファイザー インク. | 4−ヘテロサイクリル−置換キナゾリン誘導体、その調製法および抗癌剤としてのその使用法 |
| WO1995024190A2 (en) * | 1994-03-07 | 1995-09-14 | Sugen, Inc. | Receptor tyrosine kinase inhibitors for inhibiting cell proliferative disorders and compositions thereof |
| DK0682027T3 (da) * | 1994-05-03 | 1998-05-04 | Ciba Geigy Ag | Pyrrolopyrimidinderivater med antiproliferativ virkning |
| DE19503151A1 (de) * | 1995-02-01 | 1996-08-08 | Thomae Gmbh Dr K | Pyrimido[5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| TW414798B (en) * | 1994-09-07 | 2000-12-11 | Thomae Gmbh Dr K | Pyrimido (5,4-d) pyrimidines, medicaments comprising these compounds, their use and processes for their preparation |
| GB9510757D0 (en) * | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
| TW321649B (enExample) * | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
| GB9424233D0 (en) * | 1994-11-30 | 1995-01-18 | Zeneca Ltd | Quinazoline derivatives |
| WO1996029331A1 (de) * | 1995-03-20 | 1996-09-26 | Dr. Karl Thomae Gmbh | Imidazochinazoline, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| DE69536015D1 (de) * | 1995-03-30 | 2009-12-10 | Pfizer Prod Inc | Chinazolinone Derivate |
| AU711592B2 (en) * | 1995-04-03 | 1999-10-14 | Novartis Ag | Pyrazole derivatives and processes for the preparation thereof |
| DE19513330A1 (de) * | 1995-04-03 | 1996-10-10 | Schering Ag | Neues Verfahren zur Herstellung von Nucleosiden |
| WO1996033977A1 (en) * | 1995-04-27 | 1996-10-31 | Zeneca Limited | Quinazoline derivatives |
| GB9508538D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| GB9508537D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| GB9508535D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivative |
| GB9508565D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quiazoline derivative |
| IL117923A (en) * | 1995-05-03 | 2000-06-01 | Warner Lambert Co | Anti-cancer pharmaceutical compositions containing polysubstituted pyrido¬2,3-d¾pyrimidine derivatives and certain such novel compounds |
| US6020492A (en) * | 1995-05-12 | 2000-02-01 | Neurogen Corporation | Deazapurine derivatives; a new class of CRF1 specific ligands |
| JP3290666B2 (ja) * | 1995-06-07 | 2002-06-10 | ファイザー・インコーポレーテッド | 複素環式の縮合環ピリミジン誘導体 |
| EP0832073B1 (en) * | 1995-06-07 | 2002-01-16 | Sugen, Inc. | Quinazolines and pharmaceutical compositions |
| DK0836605T3 (da) * | 1995-07-06 | 2002-05-13 | Novartis Ag | Pyrrolopyrimidiner og fremgangsmåder til deres fremstilling |
| GB9514265D0 (en) * | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
| GB9520822D0 (en) * | 1995-10-11 | 1995-12-13 | Wellcome Found | Therapeutically active 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 |
| GB9624482D0 (en) * | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| US5760041A (en) * | 1996-02-05 | 1998-06-02 | American Cyanamid Company | 4-aminoquinazoline EGFR Inhibitors |
| EP0837063A1 (en) * | 1996-10-17 | 1998-04-22 | Pfizer Inc. | 4-Aminoquinazoline derivatives |
-
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009007364A (ja) * | 1996-10-15 | 2009-01-15 | Astrazeneca Uk Ltd | キナゾリン誘導体 |
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