JP2000506160A - 神経学的に活性な試剤としてのアゾロベンズアゼピン誘導体 - Google Patents
神経学的に活性な試剤としてのアゾロベンズアゼピン誘導体Info
- Publication number
- JP2000506160A JP2000506160A JP9531562A JP53156297A JP2000506160A JP 2000506160 A JP2000506160 A JP 2000506160A JP 9531562 A JP9531562 A JP 9531562A JP 53156297 A JP53156297 A JP 53156297A JP 2000506160 A JP2000506160 A JP 2000506160A
- Authority
- JP
- Japan
- Prior art keywords
- lower alkyl
- phenyl
- group
- chloro
- compound
- 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.)
- Ceased
Links
- 239000013543 active substance Substances 0.000 title description 2
- 239000001257 hydrogen Substances 0.000 claims abstract description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 63
- 238000000034 method Methods 0.000 claims abstract description 55
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 37
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 28
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 23
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 23
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 20
- 150000002367 halogens Chemical class 0.000 claims abstract description 20
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 8
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 243
- 125000000217 alkyl group Chemical group 0.000 claims description 212
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 139
- -1 ha Logen Chemical group 0.000 claims description 124
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 87
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 68
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 46
- 150000003839 salts Chemical class 0.000 claims description 46
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 125000000304 alkynyl group Chemical group 0.000 claims description 30
- 125000003282 alkyl amino group Chemical group 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 26
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 22
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
- 125000004432 carbon atom Chemical group C* 0.000 claims description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 125000002757 morpholinyl group Chemical group 0.000 claims description 15
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 12
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 10
- BYGJDSSWGMQHFV-UHFFFAOYSA-N ethyl 7-chloro-4,10-dioxo-2,5-dihydropyrazolo[3,4-c][1]benzazepine-1-carboxylate Chemical compound O=C1C2=CC=C(Cl)C=C2NC(=O)C2=C1C(C(=O)OCC)=NN2 BYGJDSSWGMQHFV-UHFFFAOYSA-N 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 230000002378 acidificating effect Effects 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 239000003981 vehicle Substances 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000004193 piperazinyl group Chemical group 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 125000006030 1-methyl-3-butenyl group Chemical group 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims description 4
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 claims description 4
- 125000006032 3-methyl-3-butenyl group Chemical group 0.000 claims description 4
- DPNCXWXBCBWRNJ-UHFFFAOYSA-N 7-chloro-1-(trifluoromethyl)-2,5-dihydropyrazolo[3,4-c][1]benzazepine-4,10-dione Chemical compound O=C1C2=CC=C(Cl)C=C2NC(=O)C2=C1C(C(F)(F)F)=NN2 DPNCXWXBCBWRNJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
- WXKSZEDCFWOBRB-UHFFFAOYSA-N 7-chloro-4,10-dioxo-3,5-dihydropyrazolo[3,4-c][1]benzazepine-1-carbonitrile Chemical compound C=1C(Cl)=CC=C(C2=O)C=1NC(=O)C1=C2C(C#N)=NN1 WXKSZEDCFWOBRB-UHFFFAOYSA-N 0.000 claims description 3
- 150000003863 ammonium salts Chemical class 0.000 claims description 3
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 claims description 3
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000004372 methylthioethyl group Chemical group [H]C([H])([H])SC([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004373 methylthiopropyl group Chemical group [H]C([H])([H])SC([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004344 phenylpropyl group Chemical group 0.000 claims description 3
- UJPWYEVSNNUVEO-UHFFFAOYSA-N propan-2-yl 7-chloro-4,10-dioxo-2,5-dihydropyrazolo[3,4-c][1]benzazepine-1-carboxylate Chemical compound O=C1C2=CC=C(Cl)C=C2NC(=O)C2=C1C(C(=O)OC(C)C)=NN2 UJPWYEVSNNUVEO-UHFFFAOYSA-N 0.000 claims description 3
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 2
- BBEUEVBKSSNESA-UHFFFAOYSA-N butyl 7-chloro-4,10-dioxo-2,5-dihydropyrazolo[3,4-c][1]benzazepine-1-carboxylate Chemical compound O=C1C2=CC=C(Cl)C=C2NC(=O)C2=C1C(C(=O)OCCCC)=NN2 BBEUEVBKSSNESA-UHFFFAOYSA-N 0.000 claims description 2
- ACJICPWKQJITJS-UHFFFAOYSA-N methyl 7-chloro-4,10-dioxo-2,5-dihydropyrazolo[3,4-c][1]benzazepine-1-carboxylate Chemical compound O=C1C2=CC=C(Cl)C=C2NC(=O)C2=C1C(C(=O)OC)=NN2 ACJICPWKQJITJS-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- XSXVTKBWHWTWDZ-UHFFFAOYSA-N propyl 7-chloro-4,10-dioxo-2,5-dihydropyrazolo[3,4-c][1]benzazepine-1-carboxylate Chemical compound O=C1C2=CC=C(Cl)C=C2NC(=O)C2=C1C(C(=O)OCCC)=NN2 XSXVTKBWHWTWDZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 16
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 2
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims 2
- 125000001425 triazolyl group Chemical group 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 208000025966 Neurological disease Diseases 0.000 abstract description 4
- 150000001721 carbon Chemical group 0.000 abstract 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 abstract 1
- PLKKXWBJOVTVEU-UHFFFAOYSA-N pyrrolo[2,3-i][1]benzazepine Chemical class C1=CC=NC2=C3C=CN=C3C=CC2=C1 PLKKXWBJOVTVEU-UHFFFAOYSA-N 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 147
- 239000000243 solution Substances 0.000 description 126
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 117
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 108
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 99
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- 239000007787 solid Substances 0.000 description 77
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 61
- 239000000203 mixture Substances 0.000 description 61
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
- 239000011541 reaction mixture Substances 0.000 description 47
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 42
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- 238000007792 addition Methods 0.000 description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
- 239000002904 solvent Substances 0.000 description 28
- 238000003818 flash chromatography Methods 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
- 239000010410 layer Substances 0.000 description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
- 239000000706 filtrate Substances 0.000 description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 21
- 239000012044 organic layer Substances 0.000 description 21
- 239000000843 powder Substances 0.000 description 21
- 239000000047 product Substances 0.000 description 21
- 238000003756 stirring Methods 0.000 description 20
- 239000002198 insoluble material Substances 0.000 description 18
- 125000003226 pyrazolyl group Chemical group 0.000 description 18
- 239000003960 organic solvent Substances 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 16
- 239000002585 base Substances 0.000 description 16
- 238000010992 reflux Methods 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 238000001914 filtration Methods 0.000 description 14
- 238000004587 chromatography analysis Methods 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 238000009835 boiling Methods 0.000 description 12
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
- 229960000583 acetic acid Drugs 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000012141 concentrate Substances 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 239000012065 filter cake Substances 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- YWUIUNGMQOICND-UHFFFAOYSA-N (2z)-2-diazo-1,1,1-trifluoroethane Chemical compound FC(F)(F)C=[N+]=[N-] YWUIUNGMQOICND-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 150000003852 triazoles Chemical group 0.000 description 8
- 239000004471 Glycine Substances 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 230000006378 damage Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000002002 slurry Substances 0.000 description 7
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 7
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- QDWJUBJKEHXSMT-UHFFFAOYSA-N boranylidynenickel Chemical compound [Ni]#B QDWJUBJKEHXSMT-UHFFFAOYSA-N 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 230000000302 ischemic effect Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
- 239000005695 Ammonium acetate Substances 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 206010061216 Infarction Diseases 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 235000019257 ammonium acetate Nutrition 0.000 description 4
- 229940043376 ammonium acetate Drugs 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 230000007574 infarction Effects 0.000 description 4
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 238000000159 protein binding assay Methods 0.000 description 4
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
- 210000000463 red nucleus Anatomy 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- MZPNQUMLOFWSEK-UHFFFAOYSA-N 4-chloro-2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC(Cl)=CC=C1C=O MZPNQUMLOFWSEK-UHFFFAOYSA-N 0.000 description 3
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
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- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
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- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
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- 208000020016 psychiatric disease Diseases 0.000 description 1
- NPRDHMWYZHSAHR-UHFFFAOYSA-N pyridine;trioxochromium Chemical compound O=[Cr](=O)=O.C1=CC=NC=C1.C1=CC=NC=C1 NPRDHMWYZHSAHR-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 102220240796 rs553605556 Human genes 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
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- MNIMQYYYRRRZHR-BQYQJAHWSA-N tert-butyl (e)-3-(8-chloro-3-methoxy-2,5-dioxo-1h-1-benzazepin-4-yl)prop-2-enoate Chemical compound N1C(=O)C(OC)=C(\C=C\C(=O)OC(C)(C)C)C(=O)C2=CC=C(Cl)C=C21 MNIMQYYYRRRZHR-BQYQJAHWSA-N 0.000 description 1
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- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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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- A—HUMAN NECESSITIES
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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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Psychology (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1352896P | 1996-03-08 | 1996-03-08 | |
| US60/013,528 | 1996-03-08 | ||
| PCT/GB1997/000592 WO1997032883A1 (en) | 1996-03-08 | 1997-03-04 | Azolobenzazepine derivatives as neurologically active agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2000506160A true JP2000506160A (ja) | 2000-05-23 |
| JP2000506160A5 JP2000506160A5 (cg-RX-API-DMAC10.html) | 2004-11-25 |
Family
ID=21760422
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9531562A Ceased JP2000506160A (ja) | 1996-03-08 | 1997-03-04 | 神経学的に活性な試剤としてのアゾロベンズアゼピン誘導体 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US6124281A (cg-RX-API-DMAC10.html) |
| EP (1) | EP0888350A1 (cg-RX-API-DMAC10.html) |
| JP (1) | JP2000506160A (cg-RX-API-DMAC10.html) |
| KR (1) | KR19990087585A (cg-RX-API-DMAC10.html) |
| CN (1) | CN1084747C (cg-RX-API-DMAC10.html) |
| AU (1) | AU723860B2 (cg-RX-API-DMAC10.html) |
| CA (1) | CA2247453A1 (cg-RX-API-DMAC10.html) |
| IL (1) | IL126095A0 (cg-RX-API-DMAC10.html) |
| NO (1) | NO984106L (cg-RX-API-DMAC10.html) |
| NZ (1) | NZ330973A (cg-RX-API-DMAC10.html) |
| TW (1) | TW486480B (cg-RX-API-DMAC10.html) |
| WO (1) | WO1997032883A1 (cg-RX-API-DMAC10.html) |
| ZA (1) | ZA971964B (cg-RX-API-DMAC10.html) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU744636B2 (en) * | 1997-09-29 | 2002-02-28 | Meiji Seika Pharma Co., Ltd. | Tricyclic triazolobenzazepine derivatives, process for producing the same, and antiallergic |
| US7919109B2 (en) * | 1999-02-08 | 2011-04-05 | Intarcia Therapeutics, Inc. | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicles |
| US7258869B1 (en) | 1999-02-08 | 2007-08-21 | Alza Corporation | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicle |
| ATE410427T1 (de) | 2001-12-26 | 2008-10-15 | Meiji Seika Kaisha | Neues kristallines tricyclisches triazolobenzazepinderivat |
| WO2003066634A1 (en) * | 2002-02-07 | 2003-08-14 | Neurogen Corporation | Substituted fused pyrazolecarboxylic acid arylamides and related compounds |
| US7731947B2 (en) | 2003-11-17 | 2010-06-08 | Intarcia Therapeutics, Inc. | Composition and dosage form comprising an interferon particle formulation and suspending vehicle |
| NZ551370A (en) | 2004-05-14 | 2009-08-28 | Millennium Pharm Inc | Compounds and methods for inhibiting mitotic progression by inhibiting of aurora kinase |
| US11246913B2 (en) | 2005-02-03 | 2022-02-15 | Intarcia Therapeutics, Inc. | Suspension formulation comprising an insulinotropic peptide |
| WO2006083761A2 (en) | 2005-02-03 | 2006-08-10 | Alza Corporation | Solvent/polymer solutions as suspension vehicles |
| WO2007140416A2 (en) | 2006-05-30 | 2007-12-06 | Intarcia Therapeutics, Inc. | Two-piece, internal-channel osmotic delivery system flow modulator |
| JP5048773B2 (ja) | 2006-08-09 | 2012-10-17 | インターシア セラピューティクス，インコーポレイティド | 浸透圧式デリバリーシステム及びピストンアセンブリー |
| CL2007003244A1 (es) * | 2006-11-16 | 2008-04-04 | Millennium Pharm Inc | Compuestos derivados de pirimido[5,4-d][2]benzazepina; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento del cancer. |
| NZ580447A (en) | 2007-04-23 | 2011-06-30 | Intarcia Therapeutics Inc | Suspension formulations of insulinotropic peptides and uses thereof |
| CA2726861C (en) | 2008-02-13 | 2014-05-27 | Intarcia Therapeutics, Inc. | Devices, formulations, and methods for delivery of multiple beneficial agents |
| CA2747326C (en) | 2008-12-22 | 2017-05-16 | Millennium Pharmaceuticals, Inc. | Combination of aurora kinase inhibitors and anti-cd20 antibodies |
| JO3635B1 (ar) | 2009-05-18 | 2020-08-27 | Millennium Pharm Inc | مركبات صيدلانية صلبة وطرق لانتاجها |
| RU2753280C2 (ru) | 2009-09-28 | 2021-08-12 | Интарсия Терапьютикс, Инк. | Быстрое достижение и/или прекращение существенной стабильной доставки лекарственного средства |
| BR112012020557A8 (pt) | 2010-02-19 | 2018-01-02 | Millennium Pharm Inc | formas cristalinas de 4-{[9-cloro-7-(2-flúor-6-metoifenil)-5h-pirimido[5,4-d][2]benzazepin-2-il]amino}-2-metoxibenzoato de sódio |
| US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
| US20130303519A1 (en) | 2012-03-20 | 2013-11-14 | Millennium Pharmaceuticals, Inc. | Methods of treating cancer using aurora kinase inhibitors |
| CA2907726A1 (en) | 2013-03-22 | 2014-09-25 | Millennium Pharmaceuticals, Inc. | Combination of catalytic mtorc1/2 inhibitors and selective inhibitors of aurora a kinase |
| US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
| ES2968262T3 (es) | 2015-06-03 | 2024-05-08 | I2O Therapeutics Inc | Sistemas de colocación de implantes |
| US20180207173A1 (en) | 2015-07-21 | 2018-07-26 | Millennium Pharmaceuticals, Inc. | Administration of aurora kinase inhibitor and chemotherapeutic agents |
| CN109310743A (zh) | 2016-05-16 | 2019-02-05 | 因塔西亚制药公司 | 胰高血糖素受体选择性多肽及其使用方法 |
| USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
| USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
| MX2019008006A (es) | 2017-01-03 | 2019-08-29 | Intarcia Therapeutics Inc | Metodos que comprenden la administracion continua de un agonista del receptor de glp-1 y la co-administracion de un farmaco. |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9311948D0 (en) * | 1993-06-10 | 1993-07-28 | Zeneca Ltd | Substituted nitrogen heterocycles |
| US5686442A (en) * | 1993-12-28 | 1997-11-11 | Meiji Seika Kabushiki Kaisha | Tricyclic benzazepine and benzothiazepine derivatives |
| EP0834512A4 (en) * | 1995-06-15 | 2001-08-22 | Meiji Seika Kaisha | TRICLYCLIC BENZAZEPINE COMPOUNDS. |
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1997
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- 1997-03-04 TW TW086102601A patent/TW486480B/zh active
- 1997-03-04 AU AU22253/97A patent/AU723860B2/en not_active Ceased
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- 1997-03-04 KR KR1019980707026A patent/KR19990087585A/ko not_active Withdrawn
- 1997-03-04 CN CN97192864A patent/CN1084747C/zh not_active Expired - Fee Related
- 1997-03-04 CA CA002247453A patent/CA2247453A1/en not_active Abandoned
- 1997-03-04 WO PCT/GB1997/000592 patent/WO1997032883A1/en not_active Ceased
- 1997-03-04 EP EP97905327A patent/EP0888350A1/en not_active Withdrawn
- 1997-03-04 JP JP9531562A patent/JP2000506160A/ja not_active Ceased
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- 1997-03-06 ZA ZA9701964A patent/ZA971964B/xx unknown
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1998
- 1998-09-07 NO NO984106A patent/NO984106L/no not_active Application Discontinuation
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2000
- 2000-09-22 US US09/668,261 patent/US6313290B1/en not_active Expired - Fee Related
Also Published As
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|---|---|
| CN1084747C (zh) | 2002-05-15 |
| CA2247453A1 (en) | 1997-09-12 |
| AU2225397A (en) | 1997-09-22 |
| ZA971964B (en) | 1997-09-08 |
| NO984106D0 (no) | 1998-09-07 |
| IL126095A0 (en) | 1999-05-09 |
| NO984106L (no) | 1998-11-06 |
| KR19990087585A (ko) | 1999-12-27 |
| US6124281A (en) | 2000-09-26 |
| NZ330973A (en) | 2000-03-27 |
| US6313290B1 (en) | 2001-11-06 |
| WO1997032883A1 (en) | 1997-09-12 |
| CN1224424A (zh) | 1999-07-28 |
| EP0888350A1 (en) | 1999-01-07 |
| TW486480B (en) | 2002-05-11 |
| AU723860B2 (en) | 2000-09-07 |
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