NO318892B1 - Amidderivat, fremgangsmate for fremstilling og anvendelse derav, samt farmasoytisk sammensetning. - Google Patents
Amidderivat, fremgangsmate for fremstilling og anvendelse derav, samt farmasoytisk sammensetning. Download PDFInfo
- Publication number
- NO318892B1 NO318892B1 NO20011631A NO20011631A NO318892B1 NO 318892 B1 NO318892 B1 NO 318892B1 NO 20011631 A NO20011631 A NO 20011631A NO 20011631 A NO20011631 A NO 20011631A NO 318892 B1 NO318892 B1 NO 318892B1
- Authority
- NO
- Norway
- Prior art keywords
- formula
- alkyl
- group
- hydrogen
- 6alkyl
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 51
- 150000001408 amides Chemical class 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
- 230000008569 process Effects 0.000 title claims abstract description 7
- 239000001257 hydrogen Substances 0.000 claims abstract description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 41
- 150000003839 salts Chemical class 0.000 claims abstract description 37
- 150000002148 esters Chemical class 0.000 claims abstract description 35
- 238000001727 in vivo Methods 0.000 claims abstract description 26
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 24
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 23
- 102000004127 Cytokines Human genes 0.000 claims abstract description 23
- 108090000695 Cytokines Proteins 0.000 claims abstract description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 18
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 17
- 201000010099 disease Diseases 0.000 claims abstract description 16
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 11
- 238000011282 treatment Methods 0.000 claims abstract description 11
- 230000001404 mediated effect Effects 0.000 claims abstract description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 118
- -1 methoxy, 2-dimethylaminoethoxy, 2-diethylaminoethoxy, 2-diisopropylaminoethoxy, 3- dimethylaminopropoxy, 3-diethylaminopropoxy, 2-morpholinoethoxy, 3-morpholinopropoxy Chemical group 0.000 claims description 70
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 150000002367 halogens Chemical class 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 229920006395 saturated elastomer Polymers 0.000 claims description 20
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 17
- 125000006239 protecting group Chemical group 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 12
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000000524 functional group Chemical group 0.000 claims description 8
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Chemical group 0.000 claims description 6
- 229910052717 sulfur Chemical group 0.000 claims description 6
- 239000011593 sulfur Chemical group 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 230000029936 alkylation Effects 0.000 claims description 5
- 238000005804 alkylation reaction Methods 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 150000001204 N-oxides Chemical class 0.000 claims description 3
- 150000003855 acyl compounds Chemical class 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- JCKRUPOZHCVXTD-UHFFFAOYSA-N n-[3-[(6,7-dimethoxyquinazolin-4-yl)amino]phenyl]acetamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC(NC(C)=O)=C1 JCKRUPOZHCVXTD-UHFFFAOYSA-N 0.000 claims description 3
- BLQGAUTUIVRLHZ-UHFFFAOYSA-N n-[3-[(6,7-dimethoxyquinazolin-4-yl)amino]phenyl]benzamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC(C=1)=CC=CC=1NC(=O)C1=CC=CC=C1 BLQGAUTUIVRLHZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000005529 alkyleneoxy group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- NYOMULACPQBAEU-UHFFFAOYSA-N n-[5-[(6,7-dimethoxyquinazolin-4-yl)amino]-2-fluorophenyl]benzamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC(C=1)=CC=C(F)C=1NC(=O)C1=CC=CC=C1 NYOMULACPQBAEU-UHFFFAOYSA-N 0.000 claims description 2
- BLLLARCCJHZUIJ-UHFFFAOYSA-N n-[5-[(6,7-dimethoxyquinolin-4-yl)amino]-2-fluorophenyl]benzamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1NC(C=1)=CC=C(F)C=1NC(=O)C1=CC=CC=C1 BLLLARCCJHZUIJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
- AHLKSOXEVRYIRD-UHFFFAOYSA-N n-phenylquinazolin-2-amine Chemical compound N=1C=C2C=CC=CC2=NC=1NC1=CC=CC=C1 AHLKSOXEVRYIRD-UHFFFAOYSA-N 0.000 claims 1
- 230000008707 rearrangement Effects 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract description 2
- 125000001475 halogen functional group Chemical group 0.000 abstract 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract 1
- 125000001841 imino group Chemical group [H]N=* 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 294
- 238000005481 NMR spectroscopy Methods 0.000 description 151
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 149
- 239000000203 mixture Substances 0.000 description 144
- 239000007787 solid Substances 0.000 description 115
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
- 239000000243 solution Substances 0.000 description 84
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
- 239000000047 product Substances 0.000 description 68
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 65
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 60
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 56
- 239000007858 starting material Substances 0.000 description 47
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 44
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 42
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
- 239000011541 reaction mixture Substances 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 32
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
- 239000000725 suspension Substances 0.000 description 28
- 239000012267 brine Substances 0.000 description 27
- 239000000706 filtrate Substances 0.000 description 27
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
- 238000004440 column chromatography Methods 0.000 description 21
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 21
- 235000019341 magnesium sulphate Nutrition 0.000 description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
- 239000000377 silicon dioxide Substances 0.000 description 19
- 238000001816 cooling Methods 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 18
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 18
- 241000282414 Homo sapiens Species 0.000 description 16
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 16
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 15
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 15
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 15
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 description 15
- 239000000463 material Substances 0.000 description 14
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 239000012300 argon atmosphere Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 239000002158 endotoxin Substances 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- LLLHRNQLGUOJHP-UHFFFAOYSA-N 4-chloro-6,7-dimethoxyquinazoline Chemical compound C1=NC(Cl)=C2C=C(OC)C(OC)=CC2=N1 LLLHRNQLGUOJHP-UHFFFAOYSA-N 0.000 description 9
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 9
- 108010002352 Interleukin-1 Proteins 0.000 description 9
- 102000000589 Interleukin-1 Human genes 0.000 description 9
- 239000005909 Kieselgur Substances 0.000 description 9
- 239000003480 eluent Substances 0.000 description 9
- 229920006008 lipopolysaccharide Polymers 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 102100040247 Tumor necrosis factor Human genes 0.000 description 8
- 239000002585 base Substances 0.000 description 8
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- 108091000080 Phosphotransferase Proteins 0.000 description 7
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- 239000012258 stirred mixture Substances 0.000 description 7
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
- GDIIPKWHAQGCJF-UHFFFAOYSA-N 4-Amino-2-nitrotoluene Chemical compound CC1=CC=C(N)C=C1[N+]([O-])=O GDIIPKWHAQGCJF-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- 101100291385 Drosophila melanogaster p38a gene Proteins 0.000 description 6
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- 101000624426 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 6 Proteins 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 235000011114 ammonium hydroxide Nutrition 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 235000003599 food sweetener Nutrition 0.000 description 6
- QUUDAEVLJPIPGJ-UHFFFAOYSA-N n-(3-amino-4-methylphenyl)-2-morpholin-4-ylpyridine-4-carboxamide Chemical compound C1=C(N)C(C)=CC=C1NC(=O)C1=CC=NC(N2CCOCC2)=C1 QUUDAEVLJPIPGJ-UHFFFAOYSA-N 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
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- 239000003755 preservative agent Substances 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
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- 230000001225 therapeutic effect Effects 0.000 description 6
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
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- OJWSNNNESCSTGB-UHFFFAOYSA-N n-(5-amino-2-fluorophenyl)benzamide Chemical compound NC1=CC=C(F)C(NC(=O)C=2C=CC=CC=2)=C1 OJWSNNNESCSTGB-UHFFFAOYSA-N 0.000 description 5
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- 102000004169 proteins and genes Human genes 0.000 description 5
- ZQARTYKINKNPKF-UHFFFAOYSA-N 1-n-(6,7-dimethoxyquinazolin-4-yl)-4-fluorobenzene-1,3-diamine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(N)=C1 ZQARTYKINKNPKF-UHFFFAOYSA-N 0.000 description 4
- PRNODJBTLYFZMW-UHFFFAOYSA-N 2-(5-amino-2-chloro-4-fluorophenyl)isoindole-1,3-dione Chemical compound C1=C(F)C(N)=CC(N2C(C3=CC=CC=C3C2=O)=O)=C1Cl PRNODJBTLYFZMW-UHFFFAOYSA-N 0.000 description 4
- OUJRTEVIUYGUQY-UHFFFAOYSA-N 4-[3-(4-chloro-6-methoxyquinazolin-7-yl)oxypropyl]morpholine Chemical compound COC1=CC2=C(Cl)N=CN=C2C=C1OCCCN1CCOCC1 OUJRTEVIUYGUQY-UHFFFAOYSA-N 0.000 description 4
- WRVHQEYBCDPZEU-UHFFFAOYSA-N 4-chloro-6,7-dimethoxyquinoline Chemical compound C1=CC(Cl)=C2C=C(OC)C(OC)=CC2=N1 WRVHQEYBCDPZEU-UHFFFAOYSA-N 0.000 description 4
- ZCUFFSHMOAEEIL-UHFFFAOYSA-N 6-methoxy-7-phenylmethoxy-1h-quinazolin-4-one Chemical compound COC1=CC2=C(O)N=CN=C2C=C1OCC1=CC=CC=C1 ZCUFFSHMOAEEIL-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
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- 241000699670 Mus sp. Species 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
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- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
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- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- Health & Medical Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- External Artificial Organs (AREA)
- Mechanical Coupling Of Light Guides (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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GBGB9821338.2A GB9821338D0 (en) | 1998-10-01 | 1998-10-01 | Chemical compounds |
GBGB9906564.1A GB9906564D0 (en) | 1999-03-23 | 1999-03-23 | Chemical compounds |
PCT/GB1999/003220 WO2000020402A1 (en) | 1998-10-01 | 1999-09-27 | Chemical compounds |
Publications (3)
Publication Number | Publication Date |
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NO20011631D0 NO20011631D0 (no) | 2001-03-30 |
NO20011631L NO20011631L (no) | 2001-05-21 |
NO318892B1 true NO318892B1 (no) | 2005-05-18 |
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ID=26314441
Family Applications (1)
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NO20011631A NO318892B1 (no) | 1998-10-01 | 2001-03-30 | Amidderivat, fremgangsmate for fremstilling og anvendelse derav, samt farmasoytisk sammensetning. |
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US (2) | US6593333B1 (pt) |
EP (1) | EP1117653B1 (pt) |
JP (1) | JP2002526538A (pt) |
KR (1) | KR20010089284A (pt) |
CN (1) | CN1158266C (pt) |
AT (1) | ATE232205T1 (pt) |
AU (1) | AU761552B2 (pt) |
BR (1) | BR9914162A (pt) |
CA (1) | CA2341374A1 (pt) |
DE (1) | DE69905264T2 (pt) |
DK (1) | DK1117653T3 (pt) |
ES (1) | ES2191462T3 (pt) |
HK (1) | HK1037367A1 (pt) |
IL (2) | IL142257A0 (pt) |
NO (1) | NO318892B1 (pt) |
NZ (1) | NZ510210A (pt) |
PT (1) | PT1117653E (pt) |
WO (1) | WO2000020402A1 (pt) |
Families Citing this family (78)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7772432B2 (en) * | 1991-09-19 | 2010-08-10 | Astrazeneca Ab | Amidobenzamide derivatives which are useful as cytokine inhibitors |
GB9816837D0 (en) | 1998-08-04 | 1998-09-30 | Zeneca Ltd | Amide derivatives |
IL134723A0 (en) | 1997-09-23 | 2001-04-30 | Zeneca Ltd | Amide derivatives for the treatment of diseases mediated by cytokines |
AU749293B2 (en) | 1998-05-15 | 2002-06-20 | Astrazeneca Ab | Benzamide derivatives for the treatment of diseases mediated by cytokines |
BR9910467A (pt) | 1998-05-15 | 2001-01-09 | Astrazeneca Ab | Composto derivado de amida, processo para a preparação do mesmo, composição farmacêutica, e, uso de um composto derivado de amida |
TR200100300T2 (tr) | 1998-08-04 | 2001-07-23 | Astrazeneca Ab | Sitokinlerin üretiminde engelleyici olarak kullanışlı amid türevleri |
WO2000010563A1 (en) * | 1998-08-20 | 2000-03-02 | Smithkline Beecham Corporation | Novel substituted triazole compounds |
PL346854A1 (en) | 1998-09-25 | 2002-03-11 | Astrazeneca Ab | Benzamide derivatives and their use as cytokine inhibitors |
ES2219319T3 (es) | 1999-03-17 | 2004-12-01 | Astrazeneca Ab | Derivados de amida. |
BR0009041A (pt) | 1999-03-17 | 2001-12-26 | Astrazeneca Ab | Derivado de amida, processo para a preparação deum derivado de amida, composição farmacêutica,uso de um derivado de amida, e, método paratratar doenças ou quadros clìnicos mediados porcitocinas |
GB9906566D0 (en) | 1999-03-23 | 1999-05-19 | Zeneca Ltd | Chemical compounds |
WO2001021596A1 (en) * | 1999-09-21 | 2001-03-29 | Astrazeneca Ab | Quinazoline derivatives and their use as pharmaceuticals |
GB9924092D0 (en) * | 1999-10-13 | 1999-12-15 | Zeneca Ltd | Pyrimidine derivatives |
US6759410B1 (en) * | 1999-11-23 | 2004-07-06 | Smithline Beecham Corporation | 3,4-dihydro-(1H)-quinazolin-2-ones and their use as CSBP/p38 kinase inhibitors |
US6943161B2 (en) | 1999-12-28 | 2005-09-13 | Pharmacopela Drug Discovery, Inc. | Pyrimidine and triazine kinase inhibitors |
US7235551B2 (en) * | 2000-03-02 | 2007-06-26 | Smithkline Beecham Corporation | 1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases |
UA73993C2 (uk) | 2000-06-06 | 2005-10-17 | Астразенека Аб | Хіназолінові похідні для лікування пухлин та фармацевтична композиція |
JP4524072B2 (ja) * | 2000-10-23 | 2010-08-11 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | 新規化合物 |
ATE502928T1 (de) | 2000-11-01 | 2011-04-15 | Millennium Pharm Inc | Stickstoffhaltige heterozyklische verbindungen und verfahren zu deren herstellung |
US6867300B2 (en) | 2000-11-17 | 2005-03-15 | Bristol-Myers Squibb Company | Methods for the preparation of pyrrolotriazine compounds useful as kinase inhibitors |
AU2002350105A1 (en) | 2001-06-21 | 2003-01-08 | Ariad Pharmaceuticals, Inc. | Novel quinazolines and uses thereof |
ATE343415T1 (de) * | 2001-06-29 | 2006-11-15 | Ab Science | Die verwendung von c-kit hemmer zur behandlung von entzündlichen darmerkrankungen |
AU2003207961A1 (en) * | 2002-01-16 | 2003-07-30 | Ramot At Tel Aviv University Ltd. | Compositions and their use for enhancing and inhibiting fertilization |
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 |
DE60315826T2 (de) * | 2002-04-19 | 2008-05-21 | Smithkline Beecham Corp. | Neue verbindungen |
DE60325469D1 (de) | 2002-04-23 | 2009-02-05 | Bristol Myers Squibb Co | Als kinase inhibitoren geeignete arylketonpyrrolotriazin-verbindungen |
MXPA04010379A (es) | 2002-04-23 | 2005-02-17 | Squibb Bristol Myers Co | Compuestos de pirrolo-triazina anilina utiles como inhibidores de cinasa. |
ES2278170T3 (es) | 2002-07-09 | 2007-08-01 | BOEHRINGER INGELHEIM PHARMA GMBH & CO.KG | Composiciones farmaceuticas de anticolinergicos e inhibidores de la quinasa p38 en el tratamiento de enfermedades respiratorias. |
EP1521747B1 (en) | 2002-07-15 | 2018-09-05 | Symphony Evolution, Inc. | Receptor-type kinase modulators and methods of use |
WO2004018430A1 (ja) * | 2002-08-23 | 2004-03-04 | 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 |
GB0309850D0 (en) | 2003-04-30 | 2003-06-04 | Astrazeneca Ab | Quinazoline derivatives |
JO2785B1 (en) * | 2003-05-27 | 2014-03-15 | شركة جانسين فارماسوتيكا ان. في | Quinazoline derivatives |
GB0317665D0 (en) | 2003-07-29 | 2003-09-03 | Astrazeneca Ab | Qinazoline derivatives |
CA2537812C (en) | 2003-09-26 | 2013-01-22 | Exelixis, Inc. | C-met modulators and method of use |
GB0324790D0 (en) | 2003-10-24 | 2003-11-26 | Astrazeneca Ab | Amide derivatives |
GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
UA83881C2 (en) * | 2003-12-18 | 2008-08-26 | Янссен Фармацевтика Н.В. | Pyrido- and pyrimidopyrimidine derivatives as anti-proliferative agents |
BRPI0400869B8 (pt) * | 2004-03-02 | 2021-05-25 | Univ Estadual Campinas Unicamp | novos compostos derivados de 4-anilinoquinazolinas com propriedade inibidora de adenosinacinases |
WO2005075439A1 (en) * | 2004-02-03 | 2005-08-18 | Astrazeneca Ab | Quinazoline derivatives |
US7504521B2 (en) | 2004-08-05 | 2009-03-17 | Bristol-Myers Squibb Co. | Methods for the preparation of pyrrolotriazine compounds |
US20060035893A1 (en) | 2004-08-07 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders |
TW200618803A (en) | 2004-08-12 | 2006-06-16 | Bristol Myers Squibb Co | Process for preparing pyrrolotriazine aniline compounds useful as kinase inhibitors |
MX2007004403A (es) | 2004-10-12 | 2007-04-27 | Astrazeneca Ab | Derivados de quinazolina. |
CA2586870A1 (en) * | 2004-11-10 | 2006-05-18 | Synta Pharmaceuticals Corp. | Il-12 modulatory compounds |
NI200700147A (es) | 2004-12-08 | 2019-05-10 | Janssen Pharmaceutica Nv | Derivados de quinazolina inhibidores de cinasas dirigidos a multip |
PE20060777A1 (es) | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas |
GB0504019D0 (en) * | 2005-02-26 | 2005-04-06 | Astrazeneca Ab | Amide derivatives |
TW200724142A (en) * | 2005-03-25 | 2007-07-01 | Glaxo Group Ltd | Novel compounds |
KR20080002865A (ko) * | 2005-03-25 | 2008-01-04 | 글락소 그룹 리미티드 | 피리도[2,3-d]피리미딘-7-온 및3,4-디히드로피리미도[4,5-d]피리미딘-2(1h)-온유도체의 제조 방법 |
US20090137550A1 (en) * | 2005-03-25 | 2009-05-28 | Glaxo Group Limited | Novel Compounds |
PE20061351A1 (es) | 2005-03-25 | 2007-01-14 | Glaxo Group Ltd | COMPUESTOS 8H-PIRIDO[2,3-d]PIRIMIDIN-7-ONA 2,4,8-TRISUSTITUIDOS COMO INHIBIDORES DE LA QUINASA CSBP/RK/p38 |
WO2006108059A1 (en) * | 2005-04-06 | 2006-10-12 | Exelixis, Inc. | C-met modulators and methods of use |
WO2007034144A1 (en) | 2005-09-20 | 2007-03-29 | Astrazeneca Ab | 4- (ih-indazol-s-yl-amino)-quinazoline compounds as erbb receptor tyrosine kinase inhibitors for the treatment of cancer |
WO2007071963A2 (en) * | 2005-12-22 | 2007-06-28 | Astrazeneca Ab | Quinazoline derivatives, process for their preparation and their use as anti-cancer agents |
UY30183A1 (es) | 2006-03-02 | 2007-10-31 | Astrazeneca Ab | Derivados de quinolina |
JP2009528336A (ja) * | 2006-03-02 | 2009-08-06 | アストラゼネカ アクチボラグ | キノリン誘導体 |
WO2008002039A1 (en) * | 2006-06-28 | 2008-01-03 | Hanmi Pharm. Co., Ltd. | Quinazoline derivatives for inhibiting the growth of cancer cell |
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 |
JP5377332B2 (ja) | 2007-02-06 | 2013-12-25 | 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 | 二環式へテロ環、それらの化合物を含む薬剤、その使用及びその製法 |
EP1992344A1 (en) | 2007-05-18 | 2008-11-19 | Institut Curie | P38 alpha as a therapeutic target in pathologies linked to FGFR3 mutation |
PL2245026T3 (pl) | 2008-02-07 | 2013-01-31 | Boehringer Ingelheim Int | Spirocykliczne heterocykle, leki zawierające te związki, ich zastosowanie i sposób ich produkcji |
ES2444128T3 (es) | 2008-05-13 | 2014-02-24 | Astrazeneca Ab | Nueva SAL-554 |
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 |
CA2995880C (en) | 2009-01-16 | 2021-01-05 | Exelixis, Inc. | Processes for preparing n-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-n'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide |
UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
WO2012005343A1 (ja) | 2010-07-09 | 2012-01-12 | 第一三共株式会社 | 置換ピリジン化合物 |
BR112013022307A2 (pt) | 2011-03-04 | 2020-09-24 | Glaxosmithkline Intellectual Property (No. 2) Limited | aminoquinolinas como inibidores de quinase |
TWI547494B (zh) | 2011-08-18 | 2016-09-01 | 葛蘭素史克智慧財產發展有限公司 | 作為激酶抑制劑之胺基喹唑啉類 |
AR092530A1 (es) | 2012-09-13 | 2015-04-22 | Glaxosmithkline Llc | Compuesto de amino-quinolina, composicion farmaceutica que lo comprende y uso de dicho compuesto para la preparacion de un medicamento |
TWI592417B (zh) | 2012-09-13 | 2017-07-21 | 葛蘭素史克智慧財產發展有限公司 | 胺基喹唑啉激酶抑制劑之前藥 |
RU2662810C2 (ru) | 2013-02-21 | 2018-07-31 | Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Хиназолины в качестве ингибиторов киназы |
CN103724260A (zh) * | 2013-12-18 | 2014-04-16 | 华侨大学 | 一种苯甲酰胺衍生物及其制备方法和应用 |
CN104030980A (zh) * | 2014-06-10 | 2014-09-10 | 华侨大学 | N-(3-甲氧基-4-氯苯基)-4-[(7-氯-4-喹啉)氨基]苯甲酰胺及其制备和应用 |
CN105017149A (zh) * | 2015-06-04 | 2015-11-04 | 中国人民解放军第三〇七医院 | 具有蛋白激酶抑制活性的物质、其制备方法及应用 |
US20190060286A1 (en) | 2016-02-29 | 2019-02-28 | University Of Florida Research Foundation, Incorpo | Chemotherapeutic Methods |
CN110372666B (zh) * | 2018-04-13 | 2022-11-08 | 华东理工大学 | 喹唑啉类化合物作为egfr三突变抑制剂及其应用 |
CN111499583B (zh) * | 2020-05-22 | 2022-02-15 | 沈阳工业大学 | 喹唑啉衍生物及其作为抗肿瘤药物的应用 |
CN116478111B (zh) * | 2023-04-18 | 2023-11-17 | 烟台大学 | 一种组蛋白甲基转移酶抑制剂及其制备方法 |
Family Cites Families (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1903899A (en) | 1933-04-18 | Cabboxylic acid abylides oe the benzene sebies and process oe making | ||
DE522788C (de) | 1928-11-01 | 1931-04-15 | I G Farbenindustrie Akt Ges | Verfahren zur Darstellung von Carbonsaeurearyliden der Benzolreihe |
US1909960A (en) | 1929-08-06 | 1933-05-23 | Du Pont | Intermediate for azo dyes |
GB522788A (en) | 1938-01-18 | 1940-06-27 | Keller Alfred | Improved method and means for inking printing formes |
BE611898A (pt) | 1960-12-23 | |||
US3755332A (en) | 1971-07-01 | 1973-08-28 | Ciba Geigy Corp | Substituted 4 indazolaminoquinolines |
DE2812252A1 (de) | 1978-03-21 | 1979-10-04 | Bayer Ag | 1,2,4-triazol-blockierte polyisocyanate als vernetzer fuer lackbindemittel |
US4367328A (en) | 1981-03-05 | 1983-01-04 | The Dow Chemical Company | Epoxy resins from hydroxy benzamides |
US4524168A (en) | 1981-11-18 | 1985-06-18 | Ciba-Geigy Corporation | Process for the mass coloration of polymers |
US4749729A (en) | 1984-06-21 | 1988-06-07 | American Cyanamid Company | Epoxy resin compositions curable above 160 F. and below 250 F. |
JPS61204221A (ja) | 1985-03-07 | 1986-09-10 | Hitachi Chem Co Ltd | 熱硬化性樹脂組成物 |
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 |
AU2552492A (en) | 1991-08-23 | 1993-03-16 | United States of America as represented by The Secretary Department of Health and Human Services, The | Raf protein kinase therapeutics |
AU661533B2 (en) | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
GB9314884D0 (en) | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Tricyclic derivatives |
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 |
US5550132A (en) | 1994-06-22 | 1996-08-27 | University Of North Carolina | Hydroxyalkylammonium-pyrimidines or purines and nucleoside derivatives, useful as inhibitors of inflammatory cytokines |
EP0871444A4 (en) | 1995-08-10 | 1999-01-13 | Merck & Co Inc | 2.5 SUBSTITUTED ARYL PYRROL, THE COMPOSITIONS THAT CONTAIN AND THE USE THEREOF |
DE69634822T2 (de) | 1995-08-22 | 2006-04-27 | Japan Tobacco Inc. | Amid-verbindungen und ihre anwendung |
AR004010A1 (es) | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | Compuestos heterociclicos |
GB9603095D0 (en) * | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
GB9604926D0 (en) | 1996-03-08 | 1996-05-08 | Sandoz Ltd | Organic compounds |
EP0888335A4 (en) | 1996-03-13 | 2002-01-02 | Smithkline Beecham Corp | NEW PYRIMIDINE COMPOUNDS AND THEIR USE IN THE TREATMENT OF CYTOKININ MEDIATOR DISEASES |
JP2001506230A (ja) | 1996-08-09 | 2001-05-15 | スミスクライン・ビーチャム・コーポレイション | 新規ピペラジン含有化合物 |
GB9623833D0 (en) | 1996-11-16 | 1997-01-08 | Zeneca Ltd | Chemical compound |
CA2296014A1 (en) | 1997-07-03 | 1999-01-14 | Frank W. Hobbs | Aryl-and arylamino-substituted heterocycles as corticotropin releasing hormone antagonists |
ZA986732B (en) * | 1997-07-29 | 1999-02-02 | Warner Lambert Co | Irreversible inhibitiors of tyrosine kinases |
SI0945443T1 (en) | 1998-03-27 | 2003-08-31 | Janssen Pharmaceutica N.V. | HIV inhibiting pyrimidine derivatives |
ATE267175T1 (de) | 1998-08-27 | 2004-06-15 | Sumitomo Pharma | Pyrimidin derivate |
ES2270612T3 (es) | 1998-08-29 | 2007-04-01 | Astrazeneca Ab | Compuestos de pirimidina. |
ES2274634T3 (es) | 1998-08-29 | 2007-05-16 | Astrazeneca Ab | Compuestos de pirimidina. |
MXPA02012870A (es) * | 2000-06-22 | 2003-05-14 | Pfizer Prod Inc | Derivados biciclicos sustituidos para el tratamiento del crecimiento celular anormal. |
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- 1999-09-27 KR KR1020017003934A patent/KR20010089284A/ko not_active Application Discontinuation
- 1999-09-27 IL IL14225799A patent/IL142257A0/xx active IP Right Grant
- 1999-09-27 CA CA002341374A patent/CA2341374A1/en not_active Abandoned
- 1999-09-27 AT AT99947686T patent/ATE232205T1/de not_active IP Right Cessation
- 1999-09-27 ES ES99947686T patent/ES2191462T3/es not_active Expired - Lifetime
- 1999-09-27 BR BR9914162-0A patent/BR9914162A/pt not_active Application Discontinuation
- 1999-09-27 EP EP99947686A patent/EP1117653B1/en not_active Expired - Lifetime
- 1999-09-27 US US09/787,883 patent/US6593333B1/en not_active Expired - Fee Related
- 1999-09-27 NZ NZ510210A patent/NZ510210A/xx unknown
- 1999-09-27 AU AU61064/99A patent/AU761552B2/en not_active Ceased
- 1999-09-27 DK DK99947686T patent/DK1117653T3/da active
- 1999-09-27 PT PT99947686T patent/PT1117653E/pt unknown
- 1999-09-27 DE DE69905264T patent/DE69905264T2/de not_active Expired - Fee Related
- 1999-09-27 JP JP2000574519A patent/JP2002526538A/ja active Pending
- 1999-09-27 WO PCT/GB1999/003220 patent/WO2000020402A1/en not_active Application Discontinuation
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2001
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- 2001-03-30 NO NO20011631A patent/NO318892B1/no not_active IP Right Cessation
- 2001-11-19 HK HK01108138A patent/HK1037367A1/xx not_active IP Right Cessation
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2003
- 2003-05-20 US US10/441,084 patent/US6716847B2/en not_active Expired - Fee Related
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Publication number | Publication date |
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JP2002526538A (ja) | 2002-08-20 |
AU761552B2 (en) | 2003-06-05 |
IL142257A (en) | 2006-04-10 |
AU6106499A (en) | 2000-04-26 |
HK1037367A1 (en) | 2002-02-08 |
US6716847B2 (en) | 2004-04-06 |
KR20010089284A (ko) | 2001-09-29 |
EP1117653B1 (en) | 2003-02-05 |
WO2000020402A1 (en) | 2000-04-13 |
NZ510210A (en) | 2003-06-30 |
IL142257A0 (en) | 2002-03-10 |
DK1117653T3 (da) | 2003-05-26 |
ES2191462T3 (es) | 2003-09-01 |
CA2341374A1 (en) | 2000-04-13 |
CN1158266C (zh) | 2004-07-21 |
BR9914162A (pt) | 2001-06-26 |
ATE232205T1 (de) | 2003-02-15 |
NO20011631L (no) | 2001-05-21 |
PT1117653E (pt) | 2003-06-30 |
US20030216417A1 (en) | 2003-11-20 |
US6593333B1 (en) | 2003-07-15 |
DE69905264T2 (de) | 2003-12-11 |
EP1117653A1 (en) | 2001-07-25 |
DE69905264D1 (de) | 2003-03-13 |
CN1321151A (zh) | 2001-11-07 |
NO20011631D0 (no) | 2001-03-30 |
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