ES2241324T3 - Derivados de quinazolina. - Google Patents
Derivados de quinazolina.Info
- Publication number
- ES2241324T3 ES2241324T3 ES99947758T ES99947758T ES2241324T3 ES 2241324 T3 ES2241324 T3 ES 2241324T3 ES 99947758 T ES99947758 T ES 99947758T ES 99947758 T ES99947758 T ES 99947758T ES 2241324 T3 ES2241324 T3 ES 2241324T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- alkoxy
- methoxy
- piperidin
- ethoxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- -1 cyano, amino Chemical group 0.000 claims abstract description 262
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 258
- 150000001875 compounds Chemical class 0.000 claims abstract description 203
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 106
- 239000001257 hydrogen Substances 0.000 claims abstract description 106
- 150000003839 salts Chemical class 0.000 claims abstract description 74
- 238000000034 method Methods 0.000 claims abstract description 73
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 62
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 58
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 49
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 46
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 32
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 30
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 30
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 28
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 23
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 21
- 238000002360 preparation method Methods 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 claims abstract description 12
- 230000008728 vascular permeability Effects 0.000 claims abstract description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 10
- 241001465754 Metazoa Species 0.000 claims abstract description 9
- 230000001772 anti-angiogenic effect Effects 0.000 claims abstract description 9
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 9
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims abstract description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 5
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 125000004849 alkoxymethyl group Chemical group 0.000 claims abstract description 3
- 150000002431 hydrogen Chemical class 0.000 claims abstract 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 146
- 125000001424 substituent group Chemical group 0.000 claims description 67
- 229910052736 halogen Inorganic materials 0.000 claims description 66
- 150000002367 halogens Chemical class 0.000 claims description 66
- 229910052757 nitrogen Inorganic materials 0.000 claims description 62
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 50
- 229910052799 carbon Inorganic materials 0.000 claims description 34
- 125000004043 oxo group Chemical group O=* 0.000 claims description 32
- 229910052760 oxygen Inorganic materials 0.000 claims description 31
- 229910052717 sulfur Inorganic materials 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 22
- 150000001721 carbon Chemical group 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 18
- 125000004429 atom Chemical group 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
- 125000003386 piperidinyl group Chemical group 0.000 claims description 15
- 125000004848 alkoxyethyl group Chemical group 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 229920006395 saturated elastomer Polymers 0.000 claims description 14
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 11
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000004193 piperazinyl group Chemical group 0.000 claims description 9
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 8
- 125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 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 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 5
- RMRFFCXPLWYOOY-UHFFFAOYSA-N allyl radical Chemical group [CH2]C=C RMRFFCXPLWYOOY-UHFFFAOYSA-N 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 4
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
- XRAIRKLUFOYIFQ-UHFFFAOYSA-N 4-[3-[4-[[5-(4-chlorophenyl)-1h-pyrazol-3-yl]oxy]-6-methoxyquinazolin-7-yl]oxypropyl]morpholine Chemical compound N1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1OC(=NN1)C=C1C1=CC=C(Cl)C=C1 XRAIRKLUFOYIFQ-UHFFFAOYSA-N 0.000 claims description 4
- DOQOAOBWHHEXSW-UHFFFAOYSA-N 4-[3-[6-methoxy-4-[(5-phenyl-1h-pyrazol-3-yl)oxy]quinazolin-7-yl]oxypropyl]morpholine Chemical compound N1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1OC(=NN1)C=C1C1=CC=CC=C1 DOQOAOBWHHEXSW-UHFFFAOYSA-N 0.000 claims description 4
- ZMOXRVVUBDCFRG-UHFFFAOYSA-N 4-[3-[6-methoxy-4-[(5-pyridin-4-yl-1h-pyrazol-3-yl)oxy]quinazolin-7-yl]oxypropyl]morpholine Chemical compound N1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1OC(=NN1)C=C1C1=CC=NC=C1 ZMOXRVVUBDCFRG-UHFFFAOYSA-N 0.000 claims description 4
- CEXSLCSYMIGRRU-UHFFFAOYSA-N 6-methoxy-7-(2-methoxyethoxy)-4-[(5-phenyl-1h-pyrazol-3-yl)oxy]quinazoline Chemical compound C=12C=C(OC)C(OCCOC)=CC2=NC=NC=1OC(=NN1)C=C1C1=CC=CC=C1 CEXSLCSYMIGRRU-UHFFFAOYSA-N 0.000 claims description 4
- LYLCWAABWMSIJZ-UHFFFAOYSA-N 6-methoxy-7-(2-methoxyethoxy)-4-[[5-(4-methoxyphenyl)-1h-pyrazol-3-yl]oxy]quinazoline Chemical compound C=12C=C(OC)C(OCCOC)=CC2=NC=NC=1OC(=NN1)C=C1C1=CC=C(OC)C=C1 LYLCWAABWMSIJZ-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 4
- LDRQIAPESKISGW-UHFFFAOYSA-N 4-[3-[4-[[5-(2-fluorophenyl)-1h-pyrazol-3-yl]oxy]-6-methoxyquinazolin-7-yl]oxypropyl]morpholine Chemical compound N1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1OC(=NN1)C=C1C1=CC=CC=C1F LDRQIAPESKISGW-UHFFFAOYSA-N 0.000 claims description 3
- ZNGPHFOYGLSMFH-UHFFFAOYSA-N 4-[3-[4-[[5-(4-fluorophenyl)-1h-pyrazol-3-yl]oxy]-6-methoxyquinazolin-7-yl]oxypropyl]morpholine Chemical compound N1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1OC(=NN1)C=C1C1=CC=C(F)C=C1 ZNGPHFOYGLSMFH-UHFFFAOYSA-N 0.000 claims description 3
- GJNOSEZQSAEDBT-UHFFFAOYSA-N 4-[3-[4-[[5-(furan-3-yl)-1h-pyrazol-3-yl]oxy]-6-methoxyquinazolin-7-yl]oxypropyl]morpholine Chemical compound N1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1OC(=NN1)C=C1C=1C=COC=1 GJNOSEZQSAEDBT-UHFFFAOYSA-N 0.000 claims description 3
- TUFSFBAIBGKNLQ-UHFFFAOYSA-N 4-[3-[6-methoxy-4-[[5-(3-nitrophenyl)-1h-pyrazol-3-yl]oxy]quinazolin-7-yl]oxypropyl]morpholine Chemical compound N1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1OC(=NN1)C=C1C1=CC=CC([N+]([O-])=O)=C1 TUFSFBAIBGKNLQ-UHFFFAOYSA-N 0.000 claims description 3
- PHEVGILJEFELHN-UHFFFAOYSA-N 4-[3-[6-methoxy-4-[[5-(4-nitrophenyl)-1h-pyrazol-3-yl]oxy]quinazolin-7-yl]oxypropyl]morpholine Chemical compound N1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1OC(=NN1)C=C1C1=CC=C([N+]([O-])=O)C=C1 PHEVGILJEFELHN-UHFFFAOYSA-N 0.000 claims description 3
- MDBVRWFEYLAMBA-UHFFFAOYSA-N 6-methoxy-4-[[5-(4-methoxyphenyl)-1h-pyrazol-3-yl]oxy]-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline Chemical compound C1=CC(OC)=CC=C1C1=CC(OC=2C3=CC(OC)=C(OCC4CCN(C)CC4)C=C3N=CN=2)=NN1 MDBVRWFEYLAMBA-UHFFFAOYSA-N 0.000 claims description 3
- VXGFRTSSUJBKEZ-UHFFFAOYSA-N 6-methoxy-4-[[5-(4-methoxyphenyl)-1h-pyrazol-3-yl]oxy]-7-[2-(triazol-1-yl)ethoxy]quinazoline Chemical compound C1=CC(OC)=CC=C1C1=CC(OC=2C3=CC(OC)=C(OCCN4N=NC=C4)C=C3N=CN=2)=NN1 VXGFRTSSUJBKEZ-UHFFFAOYSA-N 0.000 claims description 3
- KVLWZXBOPQRIQZ-UHFFFAOYSA-N 6-methoxy-4-[[5-(4-methoxyphenyl)-1h-pyrazol-3-yl]oxy]-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazoline Chemical compound C1=CC(OC)=CC=C1C1=CC(OC=2C3=CC(OC)=C(OCCCN4CCN(C)CC4)C=C3N=CN=2)=NN1 KVLWZXBOPQRIQZ-UHFFFAOYSA-N 0.000 claims description 3
- CNDJEHZZDXTJAD-UHFFFAOYSA-N 6-methoxy-7-[2-(2-methoxyethoxy)ethoxy]-4-[(5-phenyl-1h-pyrazol-3-yl)oxy]quinazoline Chemical compound C=12C=C(OC)C(OCCOCCOC)=CC2=NC=NC=1OC(=NN1)C=C1C1=CC=CC=C1 CNDJEHZZDXTJAD-UHFFFAOYSA-N 0.000 claims description 3
- LATNIDZFEFGNMI-UHFFFAOYSA-N 7-(2-imidazol-1-ylethoxy)-6-methoxy-4-[(5-phenyl-1h-pyrazol-3-yl)oxy]quinazoline Chemical compound N1=CN=C2C=C(OCCN3C=NC=C3)C(OC)=CC2=C1OC(=NN1)C=C1C1=CC=CC=C1 LATNIDZFEFGNMI-UHFFFAOYSA-N 0.000 claims description 3
- TWYLGVCHEXWXMH-UHFFFAOYSA-N 7-(2-methoxyethoxy)-4-[(5-phenyl-1h-pyrazol-3-yl)oxy]quinazoline Chemical compound N=1C=NC2=CC(OCCOC)=CC=C2C=1OC(=NN1)C=C1C1=CC=CC=C1 TWYLGVCHEXWXMH-UHFFFAOYSA-N 0.000 claims description 3
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 2
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 2
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- XQXJCZQAVUTNBQ-UHFFFAOYSA-N 6-methoxy-4-[[5-(4-methoxyphenyl)-1h-pyrazol-3-yl]oxy]-7-[[1-(2-methylsulfonylethyl)piperidin-4-yl]methoxy]quinazoline Chemical compound C1=CC(OC)=CC=C1C1=CC(OC=2C3=CC(OC)=C(OCC4CCN(CCS(C)(=O)=O)CC4)C=C3N=CN=2)=NN1 XQXJCZQAVUTNBQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
- 125000002071 phenylalkoxy group Chemical group 0.000 claims description 2
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 2
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 25
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 abstract description 22
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 abstract description 20
- 238000011282 treatment Methods 0.000 abstract description 13
- 206010028980 Neoplasm Diseases 0.000 abstract description 11
- 201000010099 disease Diseases 0.000 abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
- 201000011510 cancer Diseases 0.000 abstract description 8
- 230000001603 reducing effect Effects 0.000 abstract description 7
- 230000008569 process Effects 0.000 abstract description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 4
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 2
- 125000005647 linker group Chemical group 0.000 abstract 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 134
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 93
- 239000000203 mixture Substances 0.000 description 88
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 75
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 74
- 238000001704 evaporation Methods 0.000 description 65
- 230000008020 evaporation Effects 0.000 description 64
- 238000001914 filtration Methods 0.000 description 52
- 239000007787 solid Substances 0.000 description 52
- 239000007858 starting material Substances 0.000 description 52
- 239000003039 volatile agent Substances 0.000 description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 34
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 238000006243 chemical reaction Methods 0.000 description 25
- 239000002904 solvent Substances 0.000 description 23
- 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 22
- 239000012267 brine Substances 0.000 description 22
- 238000001816 cooling Methods 0.000 description 22
- 238000000921 elemental analysis Methods 0.000 description 22
- 239000012044 organic layer Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- 238000003756 stirring Methods 0.000 description 22
- 239000000725 suspension Substances 0.000 description 22
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 21
- 239000002244 precipitate Substances 0.000 description 20
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 19
- 235000019341 magnesium sulphate Nutrition 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 238000010992 reflux Methods 0.000 description 17
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 15
- 239000012312 sodium hydride Substances 0.000 description 15
- 229910000104 sodium hydride Inorganic materials 0.000 description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 238000004090 dissolution Methods 0.000 description 13
- 235000017557 sodium bicarbonate Nutrition 0.000 description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
- 239000002585 base Substances 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 11
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 239000003701 inert diluent Substances 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- XAVZTXQALXOZJS-UHFFFAOYSA-N 4-chloro-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline Chemical compound COC1=CC2=C(Cl)N=CN=C2C=C1OCC1CCN(C)CC1 XAVZTXQALXOZJS-UHFFFAOYSA-N 0.000 description 10
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 229940022663 acetate Drugs 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- 239000012442 inert solvent Substances 0.000 description 10
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 10
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 10
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—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
- C07D401/14—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 three or more hetero rings
-
- 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
-
- 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
- C07D403/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP98402496 | 1998-10-08 | ||
| EP98402496 | 1998-10-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2241324T3 true ES2241324T3 (es) | 2005-10-16 |
Family
ID=8235527
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99947758T Expired - Lifetime ES2241324T3 (es) | 1998-10-08 | 1999-10-05 | Derivados de quinazolina. |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US7262201B1 (https=) |
| EP (1) | EP1119567B1 (https=) |
| JP (2) | JP2002527436A (https=) |
| KR (1) | KR100860295B1 (https=) |
| CN (1) | CN1161352C (https=) |
| AT (1) | ATE294796T1 (https=) |
| AU (1) | AU756556B2 (https=) |
| BR (1) | BR9914326A (https=) |
| CA (1) | CA2344290C (https=) |
| DE (1) | DE69925141T2 (https=) |
| DK (1) | DK1119567T3 (https=) |
| ES (1) | ES2241324T3 (https=) |
| HK (1) | HK1039126B (https=) |
| IL (2) | IL142359A0 (https=) |
| NO (1) | NO322644B1 (https=) |
| NZ (1) | NZ510434A (https=) |
| PT (1) | PT1119567E (https=) |
| WO (1) | WO2000021955A1 (https=) |
| ZA (1) | ZA200102655B (https=) |
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| AU2001235804A1 (en) * | 2000-03-06 | 2001-09-17 | Astrazeneca Ab | Therapy |
| ES2267748T3 (es) | 2000-04-07 | 2007-03-16 | Astrazeneca Ab | Compuestos de quinazolina. |
| UA73993C2 (uk) | 2000-06-06 | 2005-10-17 | Астразенека Аб | Хіназолінові похідні для лікування пухлин та фармацевтична композиція |
| HRP20021005A2 (en) | 2000-06-22 | 2004-02-29 | Pfizer Prod Inc | Substituted bicyclic derivatives for the treatment of abnormal cell growth |
| ATE394102T1 (de) * | 2000-06-28 | 2008-05-15 | Astrazeneca Ab | Substituierte chinazolin-derivate und deren verwendung als aurora-2-kinase inhibitoren |
| CA2419301C (en) | 2000-08-21 | 2009-12-08 | Astrazeneca Ab | Quinazoline derivatives |
| US6610677B2 (en) | 2000-09-15 | 2003-08-26 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| US7473691B2 (en) | 2000-09-15 | 2009-01-06 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| EP1317450B1 (en) | 2000-09-15 | 2006-11-22 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| RU2340611C2 (ru) * | 2000-09-15 | 2008-12-10 | Вертекс Фармасьютикалз Инкорпорейтед | Производные пиразола, используемые в качестве ингибиторов протеинкиназы |
| US6660731B2 (en) | 2000-09-15 | 2003-12-09 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| SI1318997T1 (sl) | 2000-09-15 | 2006-12-31 | Vertex Pharma | Pirazolne spojine, uporabne kot inhibitorji protein-kinaze |
| DE60144284D1 (de) | 2000-11-01 | 2011-05-05 | Millennium Pharm Inc | Stickstoffhaltige heterozyklische verbindungen und verfahren zu deren herstellung |
| EP1343782B1 (en) | 2000-12-21 | 2009-05-06 | SmithKline Beecham Corporation | Pyrimidineamines as angiogenesis modulators |
| NZ526472A (en) * | 2000-12-21 | 2004-04-30 | Vertex Pharma | Pyrazole compounds useful as protein kinase inhibitors |
| DE60229046D1 (de) | 2001-04-19 | 2008-11-06 | Astrazeneca Ab | Chinazolin derivate |
| RU2332415C2 (ru) * | 2001-04-27 | 2008-08-27 | Вертекс Фармасьютикалз Инкорпорейтед | Производные пиразола, полезные в качестве ингибиторов протеинкиназы |
| WO2003000188A2 (en) | 2001-06-21 | 2003-01-03 | Ariad Pharmaceuticals, Inc. | Novel quinazolines and uses thereof |
| DE60234125D1 (de) * | 2001-12-24 | 2009-12-03 | Astrazeneca Ab | E inhibitoren |
| JP4608215B2 (ja) | 2002-02-01 | 2011-01-12 | アストラゼネカ アクチボラグ | キナゾリン化合物 |
| MY141867A (en) | 2002-06-20 | 2010-07-16 | Vertex Pharma | Substituted pyrimidines useful as protein kinase inhibitors |
| EP2280003B1 (en) | 2002-07-15 | 2014-04-02 | Symphony Evolution, Inc. | Process for preparing receptor-type kinase modulators |
| DK1532145T3 (da) | 2002-08-02 | 2007-01-15 | Vertex Pharma | Pyrazolpræparater der er anvendelige som inhibitorer af GSK-3 |
| RU2350618C2 (ru) | 2002-11-04 | 2009-03-27 | Астразенека Аб | ПРОИЗВОДНЫЕ ХИНАЗОЛИНА В КАЧЕСТВЕ ИНГИБИТОРОВ Src ТИРОЗИНКИНАЗЫ |
| ES2290529T3 (es) * | 2002-12-24 | 2008-02-16 | Astrazeneca Ab | Derivados de fosfonooxiquinazolina y su uso farmaceutico. |
| GB0318423D0 (en) * | 2003-08-06 | 2003-09-10 | Astrazeneca Ab | Chemical compounds |
| ES2305844T3 (es) | 2003-09-16 | 2008-11-01 | Astrazeneca Ab | Derivados de quinazolina como inhibidores de tirosina cinasa. |
| PT2213661E (pt) | 2003-09-26 | 2011-12-15 | Exelixis Inc | Moduladores de c-met e métodos de uso |
| AU2004282179B2 (en) * | 2003-10-14 | 2011-05-19 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Protein kinase inhibitors |
| US20090099165A1 (en) | 2003-10-14 | 2009-04-16 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Protein Kinase Inhibitors |
| EP1802591B1 (en) * | 2004-10-12 | 2012-01-11 | AstraZeneca AB | Quinazoline derivatives |
| JP2008520713A (ja) | 2004-11-17 | 2008-06-19 | ミイカナ セラピューティクス インコーポレイテッド | キナーゼ阻害剤 |
| CA2622352C (en) | 2005-09-30 | 2014-05-27 | Miikana Therapeutics, Inc. | Substituted pyrazole compounds |
| EP1954277B1 (en) | 2005-11-03 | 2017-01-18 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines useful as kinase inhibitors |
| US20090076075A1 (en) * | 2006-03-02 | 2009-03-19 | Frederic Henri Jung | Quinoline derivatives |
| UY30183A1 (es) | 2006-03-02 | 2007-10-31 | Astrazeneca Ab | Derivados de quinolina |
| AU2008247592A1 (en) | 2007-05-02 | 2008-11-13 | Vertex Pharmaceuticals Incorporated | Thiazoles and pyrazoles useful as kinase inhibitors |
| CN101790532B (zh) | 2007-07-31 | 2013-11-20 | 沃泰克斯药物股份有限公司 | 5-氟-1H-吡唑并[3，4-b]吡啶-3-胺及其衍生物的制备方法 |
| SI2947072T1 (sl) | 2008-03-17 | 2017-03-31 | Ambit Biosciences Corporation | 1-(3-(6,7-dimetoksikinazolin-4-iloksi)fenil)-3-(5-1,1,1-trifluoro-2- metilpropan-2-il)izoksazol-3-il)urea kot modulator raf kinaze pri zdravljenju rakavih bolezni |
| WO2010027921A1 (en) | 2008-09-03 | 2010-03-11 | Vertex Pharmaceuticals Incorporated | Co-crystals and pharmaceutical formulations comprising the same |
| EP2241565A1 (en) | 2009-01-15 | 2010-10-20 | Universität Leipzig | Aurora kinase inhibitors compounds |
| SG173014A1 (en) | 2009-01-16 | 2011-08-29 | Exelixis Inc | Malate salt of n- (4- { [ 6, 7-bis (methyloxy) quin0lin-4-yl] oxy}phenyl)-n' - (4 -fluorophenyl) cyclopropane-1,1-dicarboxamide, and crystalline forms therof for the treatment of cancer |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| CN104039785A (zh) | 2011-10-06 | 2014-09-10 | 拜耳知识产权有限责任公司 | 作为杀真菌剂的杂环基吡(嘧)啶基吡唑 |
| JP6669499B2 (ja) | 2013-02-15 | 2020-03-18 | カラ ファーマシューティカルズ インコーポレイテッド | 治療用化合物 |
| JP2016510000A (ja) | 2013-02-20 | 2016-04-04 | カラ ファーマシューティカルズ インコーポレイテッド | 治療用化合物およびその使用 |
| US9688688B2 (en) | 2013-02-20 | 2017-06-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof |
| ES2640648T3 (es) | 2013-09-16 | 2017-11-03 | Astrazeneca Ab | Nanopartículas poliméricas terapéuticas y métodos para su fabricación y uso |
| NZ719185A (en) | 2013-11-01 | 2017-11-24 | Kala Pharmaceuticals Inc | Crystalline forms of therapeutic compounds and uses thereof |
| US9890173B2 (en) | 2013-11-01 | 2018-02-13 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| JP6527513B2 (ja) | 2013-11-20 | 2019-06-05 | シグナルケム・ライフサイエンシーズ・コーポレイションＳｉｇｎａｌｃｈｅｍ Ｌｉｆｅｓｃｉｅｎｃｅｓ Ｃｏｒｐｏｒａｔｉｏｎ | Ｔａｍファミリーキナーゼ阻害剤としてのキナゾリン誘導体 |
| KR20180086187A (ko) | 2015-10-05 | 2018-07-30 | 더 트러스티이스 오브 콜롬비아 유니버시티 인 더 시티 오브 뉴욕 | 자가포식 유동의 활성체 및 포스포리파제 d 및 타우를 포함하는 단백질 응집물의 클리어런스 및 단백질질환의 치료 |
| AU2017324713B2 (en) | 2016-09-08 | 2020-08-13 | KALA BIO, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| KR20190051010A (ko) | 2016-09-08 | 2019-05-14 | 칼라 파마슈티컬스, 인크. | 치료 화합물의 결정형 및 그의 용도 |
| EP3509423A4 (en) | 2016-09-08 | 2020-05-13 | Kala Pharmaceuticals, Inc. | CRYSTALLINE FORMS OF THERAPEUTIC COMPOUNDS AND USES THEREOF |
| EP3548007A4 (en) | 2016-12-01 | 2020-08-12 | Ignyta, Inc. | METHOD OF TREATMENT OF CANCER |
| JP2021515767A (ja) | 2018-03-07 | 2021-06-24 | バイエル・アクチエンゲゼルシヤフト | Ｅｒｋ５阻害剤の同定及び使用 |
| CN113549053B (zh) * | 2020-04-23 | 2022-09-13 | 沈阳中化农药化工研发有限公司 | 一种吡唑喹（唑）啉醚类化合物及其应用 |
| CN115968288B (zh) * | 2020-08-20 | 2024-08-27 | 江苏正大丰海制药有限公司 | 作为ret激酶抑制剂的杂芳环化合物及其制备和应用 |
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| US3870725A (en) | 1971-03-30 | 1975-03-11 | Lilly Industries Ltd | Nitrothiazole derivatives |
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| US5411963A (en) | 1988-01-29 | 1995-05-02 | Dowelanco | Quinazoline derivatives |
| 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 |
| AU1422392A (en) | 1991-03-22 | 1992-10-21 | Nippon Soda Co., Ltd. | 2-substituted pyridine derivative, production thereof, and agrohorticultural bactericide |
| US5409930A (en) | 1991-05-10 | 1995-04-25 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
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| 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 |
| US5714493A (en) | 1991-05-10 | 1998-02-03 | Rhone-Poulenc Rorer Pharmaceuticals, Inc. | Aryl and heteroaryl quinazoline compounds which inhibit CSF-1R receptor tyrosine kinase |
| US5480883A (en) | 1991-05-10 | 1996-01-02 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| DE4208254A1 (de) | 1992-03-14 | 1993-09-16 | Hoechst Ag | Substituierte pyrimidine, verfahren zu ihrer herstellung und ihre verwendung als schaedlingsbekaempfungsmittel und fungizid |
| 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 |
| JPH10508486A (ja) | 1994-11-07 | 1998-08-25 | メルク エンド カンパニー インコーポレーテッド | 修飾神経ペプチドｙレセプター |
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| TW334434B (en) | 1995-05-16 | 1998-06-21 | Kanebo Ltd | Novel quinazoline compound and anti-tumor agent |
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| ID19609A (id) * | 1996-07-13 | 1998-07-23 | Glaxo Group Ltd | Senyawa-senyawa heterosiklik |
| NZ330571A (en) | 1996-10-01 | 1999-10-28 | Kyowa Hakko Kogyo Kk | Nitrogenous heterocyclic compounds that may contain sulphur or oxygen |
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| GB9800575D0 (en) * | 1998-01-12 | 1998-03-11 | Glaxo Group Ltd | Heterocyclic compounds |
| UA71945C2 (en) | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
-
1999
- 1999-10-05 KR KR1020017004370A patent/KR100860295B1/ko not_active Expired - Fee Related
- 1999-10-05 CN CNB998118613A patent/CN1161352C/zh not_active Expired - Fee Related
- 1999-10-05 NZ NZ510434A patent/NZ510434A/en not_active IP Right Cessation
- 1999-10-05 PT PT99947758T patent/PT1119567E/pt unknown
- 1999-10-05 JP JP2000575861A patent/JP2002527436A/ja not_active Withdrawn
- 1999-10-05 HK HK02100744.7A patent/HK1039126B/en not_active IP Right Cessation
- 1999-10-05 AT AT99947758T patent/ATE294796T1/de active
- 1999-10-05 DE DE69925141T patent/DE69925141T2/de not_active Expired - Lifetime
- 1999-10-05 BR BR9914326-7A patent/BR9914326A/pt not_active Application Discontinuation
- 1999-10-05 US US09/806,836 patent/US7262201B1/en not_active Expired - Fee Related
- 1999-10-05 AU AU61128/99A patent/AU756556B2/en not_active Ceased
- 1999-10-05 IL IL14235999A patent/IL142359A0/xx unknown
- 1999-10-05 CA CA002344290A patent/CA2344290C/en not_active Expired - Fee Related
- 1999-10-05 DK DK99947758T patent/DK1119567T3/da active
- 1999-10-05 WO PCT/GB1999/003295 patent/WO2000021955A1/en not_active Ceased
- 1999-10-05 ES ES99947758T patent/ES2241324T3/es not_active Expired - Lifetime
- 1999-10-05 EP EP99947758A patent/EP1119567B1/en not_active Expired - Lifetime
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2001
- 2001-03-30 ZA ZA200102655A patent/ZA200102655B/en unknown
- 2001-04-01 IL IL142359A patent/IL142359A/en not_active IP Right Cessation
- 2001-04-06 NO NO20011739A patent/NO322644B1/no not_active IP Right Cessation
-
2011
- 2011-01-14 JP JP2011006012A patent/JP2011126888A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| IL142359A (en) | 2008-11-03 |
| NO20011739D0 (no) | 2001-04-06 |
| DK1119567T3 (da) | 2005-07-25 |
| DE69925141D1 (de) | 2005-06-09 |
| WO2000021955A1 (en) | 2000-04-20 |
| JP2002527436A (ja) | 2002-08-27 |
| EP1119567B1 (en) | 2005-05-04 |
| BR9914326A (pt) | 2001-06-26 |
| US7262201B1 (en) | 2007-08-28 |
| DE69925141T2 (de) | 2006-04-27 |
| CN1161352C (zh) | 2004-08-11 |
| NO20011739L (no) | 2001-06-07 |
| CA2344290C (en) | 2009-06-02 |
| CN1322202A (zh) | 2001-11-14 |
| ATE294796T1 (de) | 2005-05-15 |
| AU756556B2 (en) | 2003-01-16 |
| JP2011126888A (ja) | 2011-06-30 |
| AU6112899A (en) | 2000-05-01 |
| CA2344290A1 (en) | 2000-04-20 |
| NZ510434A (en) | 2003-10-31 |
| PT1119567E (pt) | 2005-08-31 |
| EP1119567A1 (en) | 2001-08-01 |
| KR100860295B1 (ko) | 2008-09-25 |
| HK1039126A1 (en) | 2002-04-12 |
| IL142359A0 (en) | 2002-03-10 |
| HK1039126B (en) | 2005-09-30 |
| NO322644B1 (no) | 2006-11-13 |
| KR20010085890A (ko) | 2001-09-07 |
| ZA200102655B (en) | 2002-09-30 |
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