DE60103033T2 - Neue phenylheteroalkylamin-derivate - Google Patents
Neue phenylheteroalkylamin-derivate Download PDFInfo
- Publication number
- DE60103033T2 DE60103033T2 DE60103033T DE60103033T DE60103033T2 DE 60103033 T2 DE60103033 T2 DE 60103033T2 DE 60103033 T DE60103033 T DE 60103033T DE 60103033 T DE60103033 T DE 60103033T DE 60103033 T2 DE60103033 T2 DE 60103033T2
- Authority
- DE
- Germany
- Prior art keywords
- chloro
- benzonitrile
- compound
- formula
- amino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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- 150000001875 compounds Chemical class 0.000 claims description 188
- 238000000034 method Methods 0.000 claims description 83
- -1 NR 6 R 7 Chemical group 0.000 claims description 56
- 150000003839 salts Chemical class 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 27
- 229910052717 sulfur Inorganic materials 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 23
- 125000003545 alkoxy group Chemical group 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 19
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 17
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 16
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 229910052727 yttrium Inorganic materials 0.000 claims description 12
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 208000027866 inflammatory disease Diseases 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 9
- 238000011321 prophylaxis Methods 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 208000002193 Pain Diseases 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 229940111134 coxibs Drugs 0.000 claims description 6
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims description 6
- 230000005764 inhibitory process Effects 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 230000002757 inflammatory effect Effects 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- RFNWSUKUCZJGFZ-MRXNPFEDSA-N (4r)-4-(2,5-dichlorophenoxy)-4-(4-fluorophenyl)-n-methylbutan-1-amine Chemical compound O([C@H](CCCNC)C=1C=CC(F)=CC=1)C1=CC(Cl)=CC=C1Cl RFNWSUKUCZJGFZ-MRXNPFEDSA-N 0.000 claims description 3
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 230000008901 benefit Effects 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- KMECBOCJLJFKTJ-INIZCTEOSA-N (3r)-3-(2,5-dichlorophenoxy)-n-methyl-4-(4-methylphenyl)butan-1-amine Chemical compound C([C@H](CCNC)OC=1C(=CC=C(Cl)C=1)Cl)C1=CC=C(C)C=C1 KMECBOCJLJFKTJ-INIZCTEOSA-N 0.000 claims description 2
- DXQJUBYNQJSPKH-HNNXBMFYSA-N (3r)-3-(2,5-dichlorophenoxy)-n-methyl-4-phenylbutan-1-amine Chemical compound C([C@H](CCNC)OC=1C(=CC=C(Cl)C=1)Cl)C1=CC=CC=C1 DXQJUBYNQJSPKH-HNNXBMFYSA-N 0.000 claims description 2
- JXTJXWVYFOIRGC-UHFFFAOYSA-N 1-[4-(2,5-dichlorophenoxy)-4-phenylbutyl]piperazine Chemical compound ClC1=CC=C(Cl)C(OC(CCCN2CCNCC2)C=2C=CC=CC=2)=C1 JXTJXWVYFOIRGC-UHFFFAOYSA-N 0.000 claims description 2
- RRBQJTSKEIWUJL-UHFFFAOYSA-N 1-[4-(2,5-dichlorophenoxy)-4-phenylbutyl]piperidin-4-ol Chemical compound C1CC(O)CCN1CCCC(C=1C=CC=CC=1)OC1=CC(Cl)=CC=C1Cl RRBQJTSKEIWUJL-UHFFFAOYSA-N 0.000 claims description 2
- ZZKHGFVETXSRDK-UHFFFAOYSA-N 1-[4-(2,5-dichlorophenoxy)-4-thiophen-2-ylbutyl]-4-methylpiperazine Chemical compound C1CN(C)CCN1CCCC(C=1SC=CC=1)OC1=CC(Cl)=CC=C1Cl ZZKHGFVETXSRDK-UHFFFAOYSA-N 0.000 claims description 2
- UBTIFTSQKLAYOE-UHFFFAOYSA-N 2-[(1-amino-6-methylheptan-4-yl)amino]-4-(trifluoromethyl)benzonitrile Chemical compound NCCCC(CC(C)C)NC1=CC(C(F)(F)F)=CC=C1C#N UBTIFTSQKLAYOE-UHFFFAOYSA-N 0.000 claims description 2
- JNNQAKOEHNBNET-CQSZACIVSA-N 2-[(1r)-4-amino-1-(furan-3-yl)butoxy]-4-chloro-5-fluorobenzonitrile Chemical compound O([C@H](CCCN)C1=COC=C1)C1=CC(Cl)=C(F)C=C1C#N JNNQAKOEHNBNET-CQSZACIVSA-N 0.000 claims description 2
- PLDOAPUZJMTNCD-UHFFFAOYSA-N 2-[(4-amino-1-phenylbutyl)amino]-4-chlorobenzonitrile Chemical compound C=1C=CC=CC=1C(CCCN)NC1=CC(Cl)=CC=C1C#N PLDOAPUZJMTNCD-UHFFFAOYSA-N 0.000 claims description 2
- GDTQOEMSLHKILE-UHFFFAOYSA-N 2-[4-amino-1-(1,3-thiazol-2-yl)butoxy]-4-chlorobenzonitrile Chemical compound N=1C=CSC=1C(CCCN)OC1=CC(Cl)=CC=C1C#N GDTQOEMSLHKILE-UHFFFAOYSA-N 0.000 claims description 2
- QCHUYECHYFCHLQ-UHFFFAOYSA-N 2-[4-amino-1-(2-methoxypyridin-3-yl)butoxy]-4-chlorobenzonitrile Chemical compound COC1=NC=CC=C1C(CCCN)OC1=CC(Cl)=CC=C1C#N QCHUYECHYFCHLQ-UHFFFAOYSA-N 0.000 claims description 2
- BIHUPSJDIQBJMG-UHFFFAOYSA-N 2-[4-amino-1-(2-oxo-1h-pyridin-3-yl)butoxy]-4-chlorobenzonitrile Chemical compound C=1C=CNC(=O)C=1C(CCCN)OC1=CC(Cl)=CC=C1C#N BIHUPSJDIQBJMG-UHFFFAOYSA-N 0.000 claims description 2
- QBQXIVSTBUZLOG-UHFFFAOYSA-N 2-[[4-(2,5-dichlorophenoxy)-4-phenylbutyl]-methylamino]ethanol Chemical compound C=1C=CC=CC=1C(CCCN(CCO)C)OC1=CC(Cl)=CC=C1Cl QBQXIVSTBUZLOG-UHFFFAOYSA-N 0.000 claims description 2
- WMGALHHWGZJOKF-UHFFFAOYSA-N 4-(2,5-dichlorophenoxy)-n-methyl-4-thiophen-2-ylbutan-1-amine Chemical compound C=1C=CSC=1C(CCCNC)OC1=CC(Cl)=CC=C1Cl WMGALHHWGZJOKF-UHFFFAOYSA-N 0.000 claims description 2
- ICJONTSMLLXXCO-UHFFFAOYSA-N 4-[2-chloro-5-(trifluoromethyl)phenoxy]-4-(1,3-thiazol-2-yl)butan-1-amine Chemical compound N=1C=CSC=1C(CCCN)OC1=CC(C(F)(F)F)=CC=C1Cl ICJONTSMLLXXCO-UHFFFAOYSA-N 0.000 claims description 2
- VGFNLQZVFKBTPY-JOCHJYFZSA-N 4-chloro-2-[(1r)-1-phenyl-4-(pyridin-3-ylmethylamino)butoxy]benzonitrile Chemical compound ClC1=CC=C(C#N)C(O[C@H](CCCNCC=2C=NC=CC=2)C=2C=CC=CC=2)=C1 VGFNLQZVFKBTPY-JOCHJYFZSA-N 0.000 claims description 2
- UOZARJXEZPWSBH-HXUWFJFHSA-N 4-chloro-2-[(1r)-1-phenyl-4-pyrrolidin-1-ylbutoxy]benzonitrile Chemical compound ClC1=CC=C(C#N)C(O[C@H](CCCN2CCCC2)C=2C=CC=CC=2)=C1 UOZARJXEZPWSBH-HXUWFJFHSA-N 0.000 claims description 2
- FAQOVRHAGUJGJJ-GOSISDBHSA-N 4-chloro-2-[(1r)-4-(2-hydroxyethylamino)-1-phenylbutoxy]benzonitrile Chemical compound O([C@H](CCCNCCO)C=1C=CC=CC=1)C1=CC(Cl)=CC=C1C#N FAQOVRHAGUJGJJ-GOSISDBHSA-N 0.000 claims description 2
- FQHJXPDAFFSZLM-LJQANCHMSA-N 4-chloro-2-[(1r)-4-(3-hydroxypropylamino)-1-phenylbutoxy]benzonitrile Chemical compound O([C@H](CCCNCCCO)C=1C=CC=CC=1)C1=CC(Cl)=CC=C1C#N FQHJXPDAFFSZLM-LJQANCHMSA-N 0.000 claims description 2
- UKNKORSKHIJECC-LJQANCHMSA-N 4-chloro-2-[(1r)-4-(cyclopropylamino)-1-phenylbutoxy]benzonitrile Chemical compound ClC1=CC=C(C#N)C(O[C@H](CCCNC2CC2)C=2C=CC=CC=2)=C1 UKNKORSKHIJECC-LJQANCHMSA-N 0.000 claims description 2
- CMTRTMNNCATGTQ-QGZVFWFLSA-N 4-chloro-2-[(1r)-4-(methylamino)-1-phenylbutoxy]benzonitrile Chemical compound O([C@H](CCCNC)C=1C=CC=CC=1)C1=CC(Cl)=CC=C1C#N CMTRTMNNCATGTQ-QGZVFWFLSA-N 0.000 claims description 2
- FXXVGHDSDZQSIZ-OAQYLSRUSA-N 4-chloro-2-[(1r)-4-[2-(1h-imidazol-5-yl)ethylamino]-1-phenylbutoxy]benzonitrile Chemical compound ClC1=CC=C(C#N)C(O[C@H](CCCNCCC=2NC=NC=2)C=2C=CC=CC=2)=C1 FXXVGHDSDZQSIZ-OAQYLSRUSA-N 0.000 claims description 2
- SIHYEEYEMBGQOD-DNVCBOLYSA-N 4-chloro-2-[(1r)-4-[[(2r)-1-hydroxypropan-2-yl]amino]-1-phenylbutoxy]benzonitrile Chemical compound O([C@H](CCCN[C@@H](CO)C)C=1C=CC=CC=1)C1=CC(Cl)=CC=C1C#N SIHYEEYEMBGQOD-DNVCBOLYSA-N 0.000 claims description 2
- SIHYEEYEMBGQOD-HNAYVOBHSA-N 4-chloro-2-[(1r)-4-[[(2s)-1-hydroxypropan-2-yl]amino]-1-phenylbutoxy]benzonitrile Chemical compound O([C@H](CCCN[C@H](CO)C)C=1C=CC=CC=1)C1=CC(Cl)=CC=C1C#N SIHYEEYEMBGQOD-HNAYVOBHSA-N 0.000 claims description 2
- BEHQHZICCZXWAO-HXUWFJFHSA-N 4-chloro-2-[(1r)-4-[ethyl(2-hydroxyethyl)amino]-1-phenylbutoxy]benzonitrile Chemical compound O([C@H](CCCN(CCO)CC)C=1C=CC=CC=1)C1=CC(Cl)=CC=C1C#N BEHQHZICCZXWAO-HXUWFJFHSA-N 0.000 claims description 2
- PTFCRSMCXDMEMX-LJQANCHMSA-N 4-chloro-2-[(1r)-4-imidazol-1-yl-1-phenylbutoxy]benzonitrile Chemical compound ClC1=CC=C(C#N)C(O[C@H](CCCN2C=NC=C2)C=2C=CC=CC=2)=C1 PTFCRSMCXDMEMX-LJQANCHMSA-N 0.000 claims description 2
- YCBPABBMUOXUTK-HXUWFJFHSA-N 4-chloro-2-[(1r)-4-morpholin-4-yl-1-phenylbutoxy]benzonitrile Chemical compound ClC1=CC=C(C#N)C(O[C@H](CCCN2CCOCC2)C=2C=CC=CC=2)=C1 YCBPABBMUOXUTK-HXUWFJFHSA-N 0.000 claims description 2
- UTTARCOGRMPBHU-OAHLLOKOSA-N 4-chloro-5-fluoro-2-[(1r)-1-(furan-3-yl)-4-(methylamino)butoxy]benzonitrile Chemical compound O([C@H](CCCNC)C1=COC=C1)C1=CC(Cl)=C(F)C=C1C#N UTTARCOGRMPBHU-OAHLLOKOSA-N 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- PFFMNXUIZGUQAZ-UHFFFAOYSA-N 4-[2-chloro-5-(trifluoromethyl)phenoxy]-4-(2-methyl-1,2,4-triazol-3-yl)butan-1-amine Chemical compound CN1N=CN=C1C(CCCN)OC1=CC(C(F)(F)F)=CC=C1Cl PFFMNXUIZGUQAZ-UHFFFAOYSA-N 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 claims 1
- 208000028774 intestinal disease Diseases 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 135
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 118
- 238000005160 1H NMR spectroscopy Methods 0.000 description 107
- 239000000047 product Substances 0.000 description 107
- 239000000243 solution Substances 0.000 description 105
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 61
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 60
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 59
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
- 239000007787 solid Substances 0.000 description 40
- 239000000284 extract Substances 0.000 description 38
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 36
- 239000002904 solvent Substances 0.000 description 35
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 32
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 31
- 238000001035 drying Methods 0.000 description 30
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 30
- 235000019341 magnesium sulphate Nutrition 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- 238000005481 NMR spectroscopy Methods 0.000 description 29
- 239000003921 oil Substances 0.000 description 26
- 239000000377 silicon dioxide Substances 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 239000012230 colorless oil Substances 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- 238000001704 evaporation Methods 0.000 description 22
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 21
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 20
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 239000000203 mixture Substances 0.000 description 19
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
- 230000008020 evaporation Effects 0.000 description 18
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 16
- 229910021529 ammonia Inorganic materials 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 14
- 102000004190 Enzymes Human genes 0.000 description 13
- 108090000790 Enzymes Proteins 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000011097 chromatography purification Methods 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 10
- SMUWKRUWTDAYKS-UHFFFAOYSA-N 4-chloro-2-hydroxybenzonitrile Chemical compound OC1=CC(Cl)=CC=C1C#N SMUWKRUWTDAYKS-UHFFFAOYSA-N 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 10
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 9
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 8
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 8
- 235000019270 ammonium chloride Nutrition 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000001530 fumaric acid Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 238000003556 assay Methods 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 235000006408 oxalic acid Nutrition 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 7
- RANCECPPZPIPNO-UHFFFAOYSA-N 2,5-dichlorophenol Chemical compound OC1=CC(Cl)=CC=C1Cl RANCECPPZPIPNO-UHFFFAOYSA-N 0.000 description 6
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- DMPJCDKTZMKYAZ-UHFFFAOYSA-N tert-butyl n-(6-methyl-4-oxoheptyl)carbamate Chemical compound CC(C)CC(=O)CCCNC(=O)OC(C)(C)C DMPJCDKTZMKYAZ-UHFFFAOYSA-N 0.000 description 1
- JEBNSNUCJQJJJT-UHFFFAOYSA-N tert-butyl n-[4-(5-chloro-2-cyanophenoxy)-4-(1,3-thiazol-2-yl)butyl]carbamate Chemical compound N=1C=CSC=1C(CCCNC(=O)OC(C)(C)C)OC1=CC(Cl)=CC=C1C#N JEBNSNUCJQJJJT-UHFFFAOYSA-N 0.000 description 1
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- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D233/64—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 substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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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
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/48—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/54—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and etherified hydroxy groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D295/08—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 bound oxygen or sulfur atoms
- C07D295/084—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 bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—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 bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/32—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Furan Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0004149.1A GB0004149D0 (en) | 2000-02-23 | 2000-02-23 | Novel compounds |
| GB0004149 | 2000-02-23 | ||
| PCT/SE2001/000370 WO2001062713A1 (en) | 2000-02-23 | 2001-02-20 | Novel phenylheteroalkylamine derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60103033D1 DE60103033D1 (de) | 2004-06-03 |
| DE60103033T2 true DE60103033T2 (de) | 2005-04-28 |
Family
ID=9886161
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60103033T Expired - Fee Related DE60103033T2 (de) | 2000-02-23 | 2001-02-20 | Neue phenylheteroalkylamin-derivate |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US6743939B2 (enExample) |
| EP (1) | EP1263714B1 (enExample) |
| JP (1) | JP2003523992A (enExample) |
| AR (1) | AR028220A1 (enExample) |
| AT (1) | ATE265422T1 (enExample) |
| AU (1) | AU2001234313A1 (enExample) |
| CO (1) | CO5290257A1 (enExample) |
| DE (1) | DE60103033T2 (enExample) |
| GB (1) | GB0004149D0 (enExample) |
| WO (1) | WO2001062713A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0004151D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel use |
| GB0004152D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel compounds |
| AR035700A1 (es) * | 2001-05-08 | 2004-06-23 | Astrazeneca Ab | Derivados de arilheteroalquilamina, composicion farmaceutica, usos de estos derivados para la fabricacion de medicamentos, metodos de tratamiento, y proceso para la preparacion de estos derivados |
| SE0102641D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| SE0102640D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| SE0202280D0 (sv) | 2002-07-19 | 2002-07-19 | Astrazeneca Ab | Novel compounds |
| SE0202279D0 (sv) * | 2002-07-19 | 2002-07-19 | Astrazeneca Ab | Novel comppounds |
| SE0203304D0 (sv) * | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Coumpounds |
| CA2858520A1 (en) | 2006-05-18 | 2007-11-29 | Pharmacyclics Inc. | Intracellular kinase inhibitors |
| DE102006031813B4 (de) * | 2006-07-07 | 2011-04-28 | Christian-Albrechts-Universität Zu Kiel | Verwendung basischer Acetophenone als Hemmstoffe von NO-Synthasen |
| CA2898610C (en) | 2013-01-21 | 2021-01-19 | Osaka University | Phenoxyalkylamine compound |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5144934B1 (enExample) * | 1969-12-09 | 1976-12-01 | ||
| JPS52941B1 (enExample) * | 1969-12-09 | 1977-01-11 | ||
| US4314081A (en) * | 1974-01-10 | 1982-02-02 | Eli Lilly And Company | Arloxyphenylpropylamines |
| FR2432500A1 (fr) * | 1978-02-24 | 1980-02-29 | Roussel Uclaf | Nouveaux derives de la benzene propanamine et leurs sels, procede de preparation et application a titre de medicaments |
| KR880007433A (ko) | 1986-12-22 | 1988-08-27 | 메리 앤 터커 | 3-아릴옥시-3-치환된 프로판아민 |
| US4902710A (en) * | 1988-12-14 | 1990-02-20 | Eli Lilly And Company | Serotonin and norepinephrine uptake inhibitors |
| US5320825A (en) * | 1991-05-01 | 1994-06-14 | Trustees Of The University Of Pennsylvania | Serotonin reuptake inhibitors for S.P.E.C.T. imaging |
| EP0576766A1 (en) | 1992-06-29 | 1994-01-05 | Novo Nordisk A/S | Propanolamine derivatives, their preparation and use |
| HN1998000118A (es) | 1997-08-27 | 1999-02-09 | Pfizer Prod Inc | 2 - aminopiridinas que contienen sustituyentes de anillos condensados. |
| HN1998000125A (es) * | 1997-08-28 | 1999-02-09 | Pfizer Prod Inc | 2-aminopiridinas con sustituyentes alcoxi ramificados |
| BR9911615A (pt) * | 1998-06-03 | 2001-02-06 | Pfizer Prod Inc | 2-aminopiridinas contendo substituintes de anel fundido como inibidores de sintase de óxido nìtrico |
-
2000
- 2000-02-23 GB GBGB0004149.1A patent/GB0004149D0/en not_active Ceased
-
2001
- 2001-02-20 EP EP01906490A patent/EP1263714B1/en not_active Expired - Lifetime
- 2001-02-20 WO PCT/SE2001/000370 patent/WO2001062713A1/en not_active Ceased
- 2001-02-20 CO CO01013432A patent/CO5290257A1/es not_active Application Discontinuation
- 2001-02-20 DE DE60103033T patent/DE60103033T2/de not_active Expired - Fee Related
- 2001-02-20 US US10/204,815 patent/US6743939B2/en not_active Expired - Fee Related
- 2001-02-20 AT AT01906490T patent/ATE265422T1/de not_active IP Right Cessation
- 2001-02-20 JP JP2001561723A patent/JP2003523992A/ja not_active Withdrawn
- 2001-02-20 AU AU2001234313A patent/AU2001234313A1/en not_active Abandoned
- 2001-02-21 AR ARP010100772A patent/AR028220A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE60103033D1 (de) | 2004-06-03 |
| EP1263714B1 (en) | 2004-04-28 |
| US6743939B2 (en) | 2004-06-01 |
| CO5290257A1 (es) | 2003-06-27 |
| GB0004149D0 (en) | 2000-04-12 |
| ATE265422T1 (de) | 2004-05-15 |
| JP2003523992A (ja) | 2003-08-12 |
| AR028220A1 (es) | 2003-04-30 |
| EP1263714A1 (en) | 2002-12-11 |
| US20030105161A1 (en) | 2003-06-05 |
| WO2001062713A1 (en) | 2001-08-30 |
| AU2001234313A1 (en) | 2001-09-03 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |