DE60222465T2 - Pyrazolopyridin-derivate als antiherpesmittel - Google Patents
Pyrazolopyridin-derivate als antiherpesmittel Download PDFInfo
- Publication number
- DE60222465T2 DE60222465T2 DE60222465T DE60222465T DE60222465T2 DE 60222465 T2 DE60222465 T2 DE 60222465T2 DE 60222465 T DE60222465 T DE 60222465T DE 60222465 T DE60222465 T DE 60222465T DE 60222465 T2 DE60222465 T2 DE 60222465T2
- Authority
- DE
- Germany
- Prior art keywords
- formula
- pyrazolo
- compound
- pyridin
- amine
- 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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- 150000005229 pyrazolopyridines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 456
- 238000000034 method Methods 0.000 claims abstract description 112
- 230000008569 process Effects 0.000 claims abstract description 40
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
- -1 4-pyridinyl Chemical group 0.000 claims description 86
- 125000000217 alkyl group Chemical group 0.000 claims description 78
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 45
- 229910052736 halogen Inorganic materials 0.000 claims description 42
- 150000002367 halogens Chemical class 0.000 claims description 40
- 238000011282 treatment Methods 0.000 claims description 39
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 36
- 125000000623 heterocyclic group Chemical group 0.000 claims description 36
- 125000003118 aryl group Chemical group 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 34
- 125000004432 carbon atom Chemical group C* 0.000 claims description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
- 201000010099 disease Diseases 0.000 claims description 29
- 150000001412 amines Chemical class 0.000 claims description 27
- 238000011321 prophylaxis Methods 0.000 claims description 26
- 238000004519 manufacturing process Methods 0.000 claims description 25
- 208000029433 Herpesviridae infectious disease Diseases 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 23
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 239000012453 solvate Substances 0.000 claims description 20
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
- 125000003342 alkenyl group Chemical group 0.000 claims description 17
- 150000004820 halides Chemical class 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 14
- 125000005843 halogen group Chemical group 0.000 claims description 14
- 241001465754 Metazoa Species 0.000 claims description 13
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 13
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 12
- 230000001590 oxidative effect Effects 0.000 claims description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 11
- 229920006395 saturated elastomer Polymers 0.000 claims description 11
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- AKXTWEMSABOQTE-UHFFFAOYSA-N 2-(2-fluoropyridin-4-yl)-3-(2-methylsulfanylpyrimidin-4-yl)pyrazolo[1,5-a]pyridine Chemical compound CSC1=NC=CC(C2=C3C=CC=CN3N=C2C=2C=C(F)N=CC=2)=N1 AKXTWEMSABOQTE-UHFFFAOYSA-N 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- HDOVUKNUBWVHOX-QMMMGPOBSA-N Valacyclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCOC(=O)[C@@H](N)C(C)C)C=N2 HDOVUKNUBWVHOX-QMMMGPOBSA-N 0.000 claims description 8
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 8
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 7
- 229960004150 aciclovir Drugs 0.000 claims description 7
- 239000003443 antiviral agent Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 229940093257 valacyclovir Drugs 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 6
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 6
- 125000002619 bicyclic group Chemical group 0.000 claims description 6
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- BOZVJZQAIHJKQF-UHFFFAOYSA-N n-cyclopentyl-4-[2-[2-(cyclopentylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-amine Chemical compound C1CCCC1NC1=NC=CC(C=2C(=C3C=CC=CN3N=2)C=2N=C(NC3CCCC3)N=CC=2)=N1 BOZVJZQAIHJKQF-UHFFFAOYSA-N 0.000 claims description 6
- MMMXYXKMCKKTND-UHFFFAOYSA-N 3-[2-(cyclopentylamino)pyrimidin-4-yl]-n-cyclopropyl-2-(furan-2-yl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1CC1NC1=CC=CC2=C(C=3N=C(NC4CCCC4)N=CC=3)C(C=3OC=CC=3)=NN12 MMMXYXKMCKKTND-UHFFFAOYSA-N 0.000 claims description 5
- DSMHQEKKIDNHKB-UHFFFAOYSA-N 3-[2-(cyclopentylamino)pyrimidin-4-yl]-n-propan-2-yl-2-[2-(propan-2-ylamino)pyridin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=NC(NC(C)C)=CC(C=2C(=C3C=CC=C(NC(C)C)N3N=2)C=2N=C(NC3CCCC3)N=CC=2)=C1 DSMHQEKKIDNHKB-UHFFFAOYSA-N 0.000 claims description 5
- BXWYBXLKSLNBEJ-UHFFFAOYSA-N 4-[7-chloro-2-[2-(cyclopentylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-3-yl]-n-cyclopentylpyrimidin-2-amine Chemical compound N=1N2C(Cl)=CC=CC2=C(C=2N=C(NC3CCCC3)N=CC=2)C=1C(N=1)=CC=NC=1NC1CCCC1 BXWYBXLKSLNBEJ-UHFFFAOYSA-N 0.000 claims description 5
- KEEGPCXSSGYVIT-UHFFFAOYSA-N n-(2-methoxyethyl)-2,3-bis[2-(2-methoxyethylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound COCCNC1=NC=CC(C=2C(=C3C=CC=C(NCCOC)N3N=2)C=2N=C(NCCOC)N=CC=2)=N1 KEEGPCXSSGYVIT-UHFFFAOYSA-N 0.000 claims description 5
- GRCKZNQHTWIEOG-UHFFFAOYSA-N n-cyclopentyl-2-[2-(cyclopentylamino)pyridin-4-yl]-3-[2-(propan-2-ylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound CC(C)NC1=NC=CC(C2=C3C=CC=C(NC4CCCC4)N3N=C2C=2C=C(NC3CCCC3)N=CC=2)=N1 GRCKZNQHTWIEOG-UHFFFAOYSA-N 0.000 claims description 5
- RGMDUCGAKACWBL-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(3-methylfuran-2-yl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=COC(C=2C(=C3C=CC=C(NC4CCCC4)N3N=2)C=2N=C(NC3CCCC3)N=CC=2)=C1C RGMDUCGAKACWBL-UHFFFAOYSA-N 0.000 claims description 5
- ZBKWLCBHFXICLN-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-(furan-2-yl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1CCCC1NC1=NC=CC(C2=C3C=CC=C(NC4CCCC4)N3N=C2C=2OC=CC=2)=N1 ZBKWLCBHFXICLN-UHFFFAOYSA-N 0.000 claims description 5
- PFZCOWLKXHIVII-UHFFFAOYSA-N pyridin-1-ium-1-amine Chemical class N[N+]1=CC=CC=C1 PFZCOWLKXHIVII-UHFFFAOYSA-N 0.000 claims description 5
- MQWBATCDLYQGBX-UHFFFAOYSA-N 2-(5-bromofuran-2-yl)-n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound O1C(Br)=CC=C1C1=NN(C(NC2CCCC2)=CC=C2)C2=C1C1=CC=NC(NC2CCCC2)=N1 MQWBATCDLYQGBX-UHFFFAOYSA-N 0.000 claims description 4
- UBGAVHWBSINZFN-UHFFFAOYSA-N 3-[2-(cyclopropylamino)pyrimidin-4-yl]-n-propan-2-yl-2-[2-(propan-2-ylamino)pyridin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=NC(NC(C)C)=CC(C=2C(=C3C=CC=C(NC(C)C)N3N=2)C=2N=C(NC3CC3)N=CC=2)=C1 UBGAVHWBSINZFN-UHFFFAOYSA-N 0.000 claims description 4
- RABJHBBVBNPXDI-UHFFFAOYSA-N 4-[2,3-bis(2-morpholin-4-ylpyrimidin-4-yl)pyrazolo[1,5-a]pyridin-7-yl]morpholine Chemical compound C1COCCN1C1=NC=CC(C=2C(=C3C=CC=C(N3N=2)N2CCOCC2)C=2N=C(N=CC=2)N2CCOCC2)=N1 RABJHBBVBNPXDI-UHFFFAOYSA-N 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
- 238000005899 aromatization reaction Methods 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 239000011630 iodine Substances 0.000 claims description 4
- LOBTWFNOIAQZSJ-UHFFFAOYSA-N n-(2-methylpropyl)-2,3-bis[2-(2-methylpropylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound CC(C)CNC1=NC=CC(C=2C(=C3C=CC=C(NCC(C)C)N3N=2)C=2N=C(NCC(C)C)N=CC=2)=N1 LOBTWFNOIAQZSJ-UHFFFAOYSA-N 0.000 claims description 4
- YMCWZHBUCKQQJU-UHFFFAOYSA-N n-butyl-2,3-bis[2-(butylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound CCCCNC1=NC=CC(C=2C(=C3C=CC=C(NCCCC)N3N=2)C=2N=C(NCCCC)N=CC=2)=N1 YMCWZHBUCKQQJU-UHFFFAOYSA-N 0.000 claims description 4
- UEYZILPHQWTLPO-UHFFFAOYSA-N n-cyclopentyl-2,3-bis[2-(cyclopentylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1CCCC1NC1=NC=CC(C=2C(=C3C=CC=C(NC4CCCC4)N3N=2)C=2N=C(NC3CCCC3)N=CC=2)=N1 UEYZILPHQWTLPO-UHFFFAOYSA-N 0.000 claims description 4
- COJKEPNDFKGQKK-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopentylamino)pyridin-4-yl]-2-(furan-2-yl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1CCCC1NC1=CC(C2=C3C=CC=C(NC4CCCC4)N3N=C2C=2OC=CC=2)=CC=N1 COJKEPNDFKGQKK-UHFFFAOYSA-N 0.000 claims description 4
- XQUMSZAZNJEUCF-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(3-methylfuran-2-yl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=COC(C=2C(=C3C=CC=C(NC4CCCC4)N3N=2)C=2N=C(NC3CC3)N=CC=2)=C1C XQUMSZAZNJEUCF-UHFFFAOYSA-N 0.000 claims description 4
- PUKUDMGHWIXSQG-UHFFFAOYSA-N n-cyclopropyl-2,3-bis[2-(cyclopropylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1CC1NC1=NC=CC(C=2C(=C3C=CC=C(NC4CC4)N3N=2)C=2N=C(NC3CC3)N=CC=2)=N1 PUKUDMGHWIXSQG-UHFFFAOYSA-N 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 3
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000001620 monocyclic carbocycle group Chemical group 0.000 claims description 3
- FDRVWGCQSKBAMK-UHFFFAOYSA-N n-benzyl-2,3-bis[2-(benzylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound C=1C=CC=CC=1CNC(N=1)=NC=CC=1C(C(=C1C=CC=2)C=3N=C(NCC=4C=CC=CC=4)N=CC=3)=NN1C=2NCC1=CC=CC=C1 FDRVWGCQSKBAMK-UHFFFAOYSA-N 0.000 claims description 3
- WNNCISRUMZUUQA-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopentylamino)pyridin-4-yl]-2-(2-methyl-1,3-thiazol-4-yl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound S1C(C)=NC(C=2C(=C3C=CC=C(NC4CCCC4)N3N=2)C=2C=C(NC3CCCC3)N=CC=2)=C1 WNNCISRUMZUUQA-UHFFFAOYSA-N 0.000 claims description 3
- DWHPPRIWPJWOHS-UHFFFAOYSA-N n-cyclopentyl-3-[2-(cyclopentylamino)pyrimidin-4-yl]-2-pyridin-3-ylpyrazolo[1,5-a]pyridin-7-amine Chemical compound C1CCCC1NC1=NC=CC(C2=C3C=CC=C(NC4CCCC4)N3N=C2C=2C=NC=CC=2)=N1 DWHPPRIWPJWOHS-UHFFFAOYSA-N 0.000 claims description 3
- WRPLLFUBPBDTKZ-UHFFFAOYSA-N n-cyclopentyl-3-[2-(methylamino)pyrimidin-4-yl]-2-pyridin-4-ylpyrazolo[1,5-a]pyridin-7-amine Chemical compound CNC1=NC=CC(C2=C3C=CC=C(NC4CCCC4)N3N=C2C=2C=CN=CC=2)=N1 WRPLLFUBPBDTKZ-UHFFFAOYSA-N 0.000 claims description 3
- VVXYBAMCSWAHMV-UHFFFAOYSA-N n-cyclopropyl-3-[2-(cyclopropylamino)pyrimidin-4-yl]-2-(3-methylfuran-2-yl)pyrazolo[1,5-a]pyridin-7-amine Chemical compound C1=COC(C=2C(=C3C=CC=C(NC4CC4)N3N=2)C=2N=C(NC3CC3)N=CC=2)=C1C VVXYBAMCSWAHMV-UHFFFAOYSA-N 0.000 claims description 3
- PXQQVWLAWNRFRZ-UHFFFAOYSA-N n-propan-2-yl-4-[2-[2-(propan-2-ylamino)pyridin-4-yl]pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-amine Chemical compound C1=NC(NC(C)C)=CC(C=2C(=C3C=CC=CN3N=2)C=2N=C(NC(C)C)N=CC=2)=C1 PXQQVWLAWNRFRZ-UHFFFAOYSA-N 0.000 claims description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000002346 iodo group Chemical group I* 0.000 claims description 2
- CYZVBAZTJNJPCM-UHFFFAOYSA-N n-propan-2-yl-2,3-bis[2-(propan-2-ylamino)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-7-amine Chemical compound CC(C)NC1=NC=CC(C=2C(=C3C=CC=C(NC(C)C)N3N=2)C=2N=C(NC(C)C)N=CC=2)=N1 CYZVBAZTJNJPCM-UHFFFAOYSA-N 0.000 claims description 2
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- 239000000243 solution Substances 0.000 description 101
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- 235000019341 magnesium sulphate Nutrition 0.000 description 37
- 238000002360 preparation method Methods 0.000 description 32
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- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
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- 235000020374 simple syrup Nutrition 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- JJICLMJFIKGAAU-UHFFFAOYSA-M sodium;2-amino-9-(1,3-dihydroxypropan-2-yloxymethyl)purin-6-olate Chemical compound [Na+].NC1=NC([O-])=C2N=CN(COC(CO)CO)C2=N1 JJICLMJFIKGAAU-UHFFFAOYSA-M 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
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- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
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- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012956 testing procedure Methods 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 239000004308 thiabendazole Substances 0.000 description 1
- WJCNZQLZVWNLKY-UHFFFAOYSA-N thiabendazole Chemical compound S1C=NC(C=2NC3=CC=CC=C3N=2)=C1 WJCNZQLZVWNLKY-UHFFFAOYSA-N 0.000 description 1
- 235000010296 thiabendazole Nutrition 0.000 description 1
- 229960004546 thiabendazole Drugs 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- XSROQCDVUIHRSI-UHFFFAOYSA-N thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 description 1
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 125000005208 trialkylammonium group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- LGQXXHMEBUOXRP-UHFFFAOYSA-N tributyl borate Chemical compound CCCCOB(OCCCC)OCCCC LGQXXHMEBUOXRP-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- AEHZGEDBUHMEKM-UHFFFAOYSA-N trimethyl-[2-(2-methylsulfanylpyrimidin-4-yl)ethynyl]silane Chemical compound CSC1=NC=CC(C#C[Si](C)(C)C)=N1 AEHZGEDBUHMEKM-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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- 229910052727 yttrium Inorganic materials 0.000 description 1
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33958501P | 2001-12-11 | 2001-12-11 | |
| US339585P | 2001-12-11 | ||
| PCT/US2002/037052 WO2003050120A1 (en) | 2001-12-11 | 2002-11-20 | Pyrazolo-pyridine derivatives as antiherpes agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60222465D1 DE60222465D1 (de) | 2007-10-25 |
| DE60222465T2 true DE60222465T2 (de) | 2008-06-05 |
Family
ID=23329708
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60222465T Expired - Fee Related DE60222465T2 (de) | 2001-12-11 | 2002-11-20 | Pyrazolopyridin-derivate als antiherpesmittel |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US7199120B2 (enExample) |
| EP (1) | EP1453830B1 (enExample) |
| JP (1) | JP2005516916A (enExample) |
| AT (1) | ATE373000T1 (enExample) |
| AU (1) | AU2002357740A1 (enExample) |
| DE (1) | DE60222465T2 (enExample) |
| ES (1) | ES2292839T3 (enExample) |
| WO (1) | WO2003050120A1 (enExample) |
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| AU2003217712A1 (en) | 2002-03-07 | 2003-09-22 | Smithkline Beecham Corporation | Pyrazolopyrimidine and pyrazolotriazine derivatives and pharmaceutical compositions containing them |
| AR039241A1 (es) | 2002-04-04 | 2005-02-16 | Biogen Inc | Heteroarilos trisustituidos y metodos para su produccion y uso de los mismos |
| UA80295C2 (en) | 2002-09-06 | 2007-09-10 | Biogen Inc | Pyrazolopyridines and using the same |
| US20070155738A1 (en) | 2005-05-20 | 2007-07-05 | Alantos Pharmaceuticals, Inc. | Heterobicyclic metalloprotease inhibitors |
| UA103319C2 (en) | 2008-05-06 | 2013-10-10 | Глаксосмитклайн Ллк | Thiazole- and oxazole-benzene sulfonamide compounds |
| WO2010011816A1 (en) * | 2008-07-25 | 2010-01-28 | Smithkline Beecham Corporation | Chemical compounds |
| EP2402335A1 (en) * | 2010-06-29 | 2012-01-04 | Basf Se | Pyrazolopyridine compounds |
| AU2011329486A1 (en) * | 2010-11-18 | 2013-04-18 | Glaxo Group Limited | Compounds |
| WO2013043521A1 (en) | 2011-09-22 | 2013-03-28 | Merck Sharp & Dohme Corp. | Pyrazolopyridyl compounds as aldosterone synthase inhibitors |
| US9314026B2 (en) * | 2011-10-06 | 2016-04-19 | Bayer Intellectual Property Gmbh | Heterocyclylpyri(mi)dinylpyrazole |
| TW202521536A (zh) | 2019-05-05 | 2025-06-01 | 美商基尼特奇公司 | Ｃｄｋ抑制劑 |
| WO2025202955A1 (en) | 2024-03-28 | 2025-10-02 | Pi Industries Ltd. | Fused bicyclic compounds and their use as pest control agents |
Family Cites Families (42)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP0151962A3 (en) * | 1984-01-25 | 1985-10-02 | Beecham Group Plc | Pyrazolopyridine derivatives |
| GB8404586D0 (en) * | 1984-02-22 | 1984-03-28 | Beecham Group Plc | Compounds |
| GB8404584D0 (en) * | 1984-02-22 | 1984-03-28 | Beecham Group Plc | Compounds |
| US5002941A (en) | 1985-12-12 | 1991-03-26 | Smithkline Beecham Corporation | Pyrrolo(1,2-a)imidazole and imidazo(1,2-a)pyridine derivatives and their use as 5-lipoxygenase pathway inhibitors |
| US4925849A (en) * | 1987-06-15 | 1990-05-15 | Fujisawa Pharmaceutical Company, Ltd. | Pharmaceutically useful pyrazolopyridines |
| US5155114A (en) * | 1989-01-23 | 1992-10-13 | Fujisawa Pharmaceutical Company, Ltd. | Method of treatment using pyrazolopyridine compound |
| GB8901423D0 (en) * | 1989-01-23 | 1989-03-15 | Fujisawa Pharmaceutical Co | Pyrazolopyridine compound and processes for preparation thereof |
| AU6355190A (en) | 1989-06-13 | 1991-01-17 | Smithkline Beecham Corporation | Inhibition of interleukin-1 and tumor necrosis factor production by monocytes and/or macrophages |
| AU622330B2 (en) | 1989-06-23 | 1992-04-02 | Takeda Chemical Industries Ltd. | Condensed heterocyclic compounds having a nitrogen atom in the bridgehead for use as fungicides |
| KR930700104A (ko) | 1990-06-12 | 1993-03-13 | 원본미기재 | 5-리프옥시게나제 및 사이클로옥시게나제 경로 개재된 질병의 억제 |
| GB9015764D0 (en) | 1990-07-18 | 1990-09-05 | Fujisawa Pharmaceutical Co | Pyrazolopyridine compound and processes for preparation thereof |
| EP0497258B1 (en) | 1991-01-29 | 2002-01-02 | Fujisawa Pharmaceutical Co., Ltd. | Use of adenosine antagonists in the prevention and treatment of pancreatitis and ulcer |
| GB9107513D0 (en) * | 1991-04-10 | 1991-05-29 | Fujisawa Pharmaceutical Co | Pyrazolopyridine compound and processes for preparation thereof |
| US5300478A (en) * | 1993-01-28 | 1994-04-05 | Zeneca Limited | Substituted fused pyrazolo compounds |
| US5474995A (en) | 1993-06-24 | 1995-12-12 | Merck Frosst Canada, Inc. | Phenyl heterocycles as cox-2 inhibitors |
| US5521213A (en) | 1994-08-29 | 1996-05-28 | Merck Frosst Canada, Inc. | Diaryl bicyclic heterocycles as inhibitors of cyclooxygenase-2 |
| US5552422A (en) | 1995-01-11 | 1996-09-03 | Merck Frosst Canada, Inc. | Aryl substituted 5,5 fused aromatic nitrogen compounds as anti-inflammatory agents |
| KR19980703559A (ko) | 1995-04-04 | 1998-11-05 | 그레이엄브레레톤 | 이미다조［1,2-ａ］피리딘 유도체 |
| WO1996034866A1 (en) | 1995-05-01 | 1996-11-07 | Fujisawa Pharmaceutical Co., Ltd. | Imidazo 1,2-a pyridine and imidazo 1,2-a pyridezine derivatives and their use as bone resorption inhibitors |
| US6342510B1 (en) | 1995-06-12 | 2002-01-29 | G. D. Searle & Co. | Treatment of inflammation and inflammation-related disorders with a combination of a cyclooxygenase-2 inhibitors and a leukotriene B4 receptor antagonist |
| CA2224517A1 (en) | 1995-06-12 | 1996-12-27 | G.D. Searle & Co. | Compositions comprising a cyclooxygenase-2 inhibitor and a 5-lipoxygenase inhibitor |
| US5700816A (en) * | 1995-06-12 | 1997-12-23 | Isakson; Peter C. | Treatment of inflammation and inflammation-related disorders with a combination of a cyclooxygenase-2 inhibitor and a leukotriene A4 hydrolase inhibitor |
| FR2757059B1 (fr) | 1996-12-12 | 1999-01-29 | Rhone Poulenc Rorer Sa | Nouvelle application therapeutique des derives du pyrrole |
| FR2757166B1 (fr) * | 1996-12-12 | 1999-01-29 | Rhone Poulenc Rorer Sa | Derives du pyrrole, leur preparation et les compositions pharmaceutiques qui les contiennent |
| AU7966198A (en) | 1997-06-13 | 1998-12-30 | Smithkline Beecham Corporation | Novel pyrazole and pyrazoline substituted compounds |
| ATE281458T1 (de) | 1997-09-05 | 2004-11-15 | Glaxo Group Ltd | Pharmazeutische zusammensetzung, enthaltend 2,3- diaryl-pyrazolo(1,5-b)pyridazin derivate |
| CA2331878A1 (en) | 1998-05-14 | 1999-11-18 | G.D. Searle & Co. | 1,5-diaryl substituted pyrazoles as p38 kinase inhibitors |
| US6245789B1 (en) * | 1998-05-19 | 2001-06-12 | The Procter & Gamble Company | HIV and viral treatment |
| FR2779724B1 (fr) | 1998-06-10 | 2001-04-20 | Rhone Poulenc Rorer Sa | Derives du pyrrole, leur preparation et les compositions pharmaceutiques qui les contiennent |
| US7223772B1 (en) | 1998-11-03 | 2007-05-29 | Smithkline Beecham Corporation | Pyrazolopyridine derivatives as selective cox-2 inhibitors |
| EP1157025B1 (en) | 1999-02-27 | 2004-03-10 | Glaxo Group Limited | Pyrazolopyridines |
| BR0011997A (pt) | 1999-06-28 | 2002-03-05 | Janssen Pharmaceutica Nv | Inibidores da replicação do vìrus sincicial respiratório |
| GB9919778D0 (en) | 1999-08-21 | 1999-10-27 | Zeneca Ltd | Chemical compounds |
| PE20020506A1 (es) | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
| AUPQ969800A0 (en) | 2000-08-28 | 2000-09-21 | Fujisawa Pharmaceutical Co., Ltd. | Pyrazolopyridine compound and pharmaceutical use thereof |
| AU2002239348A1 (en) | 2000-12-15 | 2002-06-24 | Glaxo Group Limited | Pyrazolopyridine derivatives |
| ATE301653T1 (de) | 2000-12-15 | 2005-08-15 | Glaxo Group Ltd | Pyrazolopyridine |
| GB0103926D0 (en) | 2001-02-17 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
| WO2002078700A1 (en) * | 2001-03-30 | 2002-10-10 | Smithkline Beecham Corporation | Pyralopyridines, process for their preparation and use as therapteutic compounds |
| EP1385847B1 (en) * | 2001-04-27 | 2005-06-01 | SmithKline Beecham Corporation | Pyrazolo[1,5-a]pyridine derivatives |
| ES2289116T3 (es) * | 2001-05-24 | 2008-02-01 | Eli Lilly And Company | Nuevos derivados de pirrol como agentes farmaceuticos. |
| WO2003000682A1 (en) | 2001-06-25 | 2003-01-03 | Merck & Co., Inc. | (pyrimidyl)(phenyl)substituted fused heteroaryl p38 inhibiting and pkg kinase inhibiting compounds |
-
2002
- 2002-11-20 ES ES02792278T patent/ES2292839T3/es not_active Expired - Lifetime
- 2002-11-20 AT AT02792278T patent/ATE373000T1/de not_active IP Right Cessation
- 2002-11-20 US US10/496,358 patent/US7199120B2/en not_active Expired - Fee Related
- 2002-11-20 JP JP2003551144A patent/JP2005516916A/ja active Pending
- 2002-11-20 DE DE60222465T patent/DE60222465T2/de not_active Expired - Fee Related
- 2002-11-20 WO PCT/US2002/037052 patent/WO2003050120A1/en not_active Ceased
- 2002-11-20 AU AU2002357740A patent/AU2002357740A1/en not_active Abandoned
- 2002-11-20 EP EP02792278A patent/EP1453830B1/en not_active Expired - Lifetime
-
2006
- 2006-11-09 US US11/558,005 patent/US20070161653A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1453830A1 (en) | 2004-09-08 |
| ATE373000T1 (de) | 2007-09-15 |
| WO2003050120A1 (en) | 2003-06-19 |
| US20070161653A1 (en) | 2007-07-12 |
| ES2292839T3 (es) | 2008-03-16 |
| JP2005516916A (ja) | 2005-06-09 |
| US20040248903A1 (en) | 2004-12-09 |
| AU2002357740A1 (en) | 2003-06-23 |
| EP1453830B1 (en) | 2007-09-12 |
| US7199120B2 (en) | 2007-04-03 |
| DE60222465D1 (de) | 2007-10-25 |
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| 8381 | Inventor (new situation) |
Inventor name: GUDMUNDSSON, KRISTJAN, RESEARCH TRIANGLE PARK,, US Inventor name: JOHNS, BRIAN A, RESEARCH TRIANGLE PARK, NC, US |
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| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |