HRP20000276A2 - Chemical compounds - Google Patents
Chemical compounds Download PDFInfo
- Publication number
- HRP20000276A2 HRP20000276A2 HR20000276A HRP20000276A HRP20000276A2 HR P20000276 A2 HRP20000276 A2 HR P20000276A2 HR 20000276 A HR20000276 A HR 20000276A HR P20000276 A HRP20000276 A HR P20000276A HR P20000276 A2 HRP20000276 A2 HR P20000276A2
- Authority
- HR
- Croatia
- Prior art keywords
- adenosine
- compound according
- group
- tetrahydro
- alk
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 174
- 229910052757 nitrogen Inorganic materials 0.000 claims description 45
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 26
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 21
- 229960005305 adenosine Drugs 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 208000002193 Pain Diseases 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 13
- 239000012453 solvate Substances 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 9
- 235000021588 free fatty acids Nutrition 0.000 claims description 9
- 208000031225 myocardial ischemia Diseases 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 230000009467 reduction Effects 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 125000001931 aliphatic group Chemical group 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 6
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 6
- 208000015114 central nervous system disease Diseases 0.000 claims description 6
- 201000002859 sleep apnea Diseases 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 208000006011 Stroke Diseases 0.000 claims description 5
- 239000000460 chlorine Chemical group 0.000 claims description 5
- 229910052801 chlorine Chemical group 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 230000009286 beneficial effect Effects 0.000 claims description 4
- 125000002619 bicyclic group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- UYSGCRYMJJMGIM-KQYNXXCUSA-N (2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COC(F)(F)F)[C@@H](O)[C@H]1O UYSGCRYMJJMGIM-KQYNXXCUSA-N 0.000 claims description 3
- FQPOPTXHKUUAGF-LSCFUAHRSA-N (2r,3r,4s,5r)-2-[2-chloro-6-(oxan-4-ylamino)purin-9-yl]-5-(3-fluoropropoxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COCCCF)O[C@H]1N1C2=NC(Cl)=NC(NC3CCOCC3)=C2N=C1 FQPOPTXHKUUAGF-LSCFUAHRSA-N 0.000 claims description 3
- FTCQFWYJINORPS-XNIJJKJLSA-N (2r,3r,4s,5r)-2-[2-methyl-6-(oxan-4-ylamino)purin-9-yl]-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical compound C=12N=CN([C@H]3[C@@H]([C@H](O)[C@@H](COC(F)(F)F)O3)O)C2=NC(C)=NC=1NC1CCOCC1 FTCQFWYJINORPS-XNIJJKJLSA-N 0.000 claims description 3
- KUUUKOXSYSLSLQ-ZRURSIFKSA-N (2r,3r,4s,5r)-2-[6-(2,3-dihydroxypropylamino)purin-9-yl]-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(NCC(O)CO)=NC=NC=2N1[C@@H]1O[C@H](COC(F)(F)F)[C@@H](O)[C@H]1O KUUUKOXSYSLSLQ-ZRURSIFKSA-N 0.000 claims description 3
- NOLDGFZSHLHTDZ-LSCFUAHRSA-N (2r,3r,4s,5r)-2-[6-(2-pyridin-4-ylethylamino)purin-9-yl]-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC(F)(F)F)O[C@H]1N1C2=NC=NC(NCCC=3C=CN=CC=3)=C2N=C1 NOLDGFZSHLHTDZ-LSCFUAHRSA-N 0.000 claims description 3
- HIDBVKBAWSBKMO-XNIJJKJLSA-N (2r,3r,4s,5r)-2-[6-(3,4-difluoroanilino)purin-9-yl]-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC(F)(F)F)O[C@H]1N1C2=NC=NC(NC=3C=C(F)C(F)=CC=3)=C2N=C1 HIDBVKBAWSBKMO-XNIJJKJLSA-N 0.000 claims description 3
- XCFCLFQNWLHHMC-XNIJJKJLSA-N (2r,3r,4s,5r)-2-[6-(3-fluoroanilino)purin-9-yl]-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC(F)(F)F)O[C@H]1N1C2=NC=NC(NC=3C=C(F)C=CC=3)=C2N=C1 XCFCLFQNWLHHMC-XNIJJKJLSA-N 0.000 claims description 3
- VLBSROBMFIQHAR-LSCFUAHRSA-N (2r,3r,4s,5r)-2-[6-(4-fluoroanilino)purin-9-yl]-5-(2,2,2-trifluoroethoxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COCC(F)(F)F)O[C@H]1N1C2=NC=NC(NC=3C=CC(F)=CC=3)=C2N=C1 VLBSROBMFIQHAR-LSCFUAHRSA-N 0.000 claims description 3
- REAFCJZEBOQFSM-XNIJJKJLSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-(2,2,2-trifluoroethoxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COCC(F)(F)F)O[C@H]1N1C2=NC=NC(NC3CCCC3)=C2N=C1 REAFCJZEBOQFSM-XNIJJKJLSA-N 0.000 claims description 3
- GLISGJNMLQTLNU-XNIJJKJLSA-N (2r,3r,4s,5r)-2-[6-(oxan-4-ylamino)purin-9-yl]-5-(2,2,2-trifluoroethoxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COCC(F)(F)F)O[C@H]1N1C2=NC=NC(NC3CCOCC3)=C2N=C1 GLISGJNMLQTLNU-XNIJJKJLSA-N 0.000 claims description 3
- ZVSMNRNJGJGCHG-SDBHATRESA-N (2r,3r,4s,5r)-2-[6-(oxan-4-ylamino)purin-9-yl]-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical group O[C@@H]1[C@H](O)[C@@H](COC(F)(F)F)O[C@H]1N1C2=NC=NC(NC3CCOCC3)=C2N=C1 ZVSMNRNJGJGCHG-SDBHATRESA-N 0.000 claims description 3
- JZHIJAIIKORZJM-QYVSTXNMSA-N (2r,3r,4s,5r)-2-[6-(tert-butylamino)purin-9-yl]-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(NC(C)(C)C)=NC=NC=2N1[C@@H]1O[C@H](COC(F)(F)F)[C@@H](O)[C@H]1O JZHIJAIIKORZJM-QYVSTXNMSA-N 0.000 claims description 3
- HNOAXRSDWGOHLH-SDBHATRESA-N (2r,3r,4s,5r)-2-[6-(thian-4-ylamino)purin-9-yl]-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC(F)(F)F)O[C@H]1N1C2=NC=NC(NC3CCSCC3)=C2N=C1 HNOAXRSDWGOHLH-SDBHATRESA-N 0.000 claims description 3
- VTGVYJFENKSVFQ-SCFUHWHPSA-N (2r,3s,4r,5r)-2-(3-fluoropropoxymethyl)-5-[6-(oxan-4-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COCCCF)O[C@H]1N1C2=NC=NC(NC3CCOCC3)=C2N=C1 VTGVYJFENKSVFQ-SCFUHWHPSA-N 0.000 claims description 3
- 125000006615 aromatic heterocyclic group Chemical class 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 229910003827 NRaRb Inorganic materials 0.000 claims description 2
- 229910006069 SO3H Inorganic materials 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 92
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 87
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 69
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 65
- 239000000243 solution Substances 0.000 description 54
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
- 239000000203 mixture Substances 0.000 description 46
- 239000000377 silicon dioxide Substances 0.000 description 45
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical class CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- 239000002904 solvent Substances 0.000 description 38
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 34
- 238000001819 mass spectrum Methods 0.000 description 30
- 235000019441 ethanol Nutrition 0.000 description 26
- 238000003818 flash chromatography Methods 0.000 description 24
- 239000013067 intermediate product Substances 0.000 description 24
- 238000010992 reflux Methods 0.000 description 24
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
- 239000000543 intermediate Substances 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 239000003921 oil Substances 0.000 description 18
- 229910021529 ammonia Inorganic materials 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 239000006260 foam Substances 0.000 description 16
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 229910052681 coesite Inorganic materials 0.000 description 9
- 229910052906 cristobalite Inorganic materials 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- -1 oxalic Chemical class 0.000 description 9
- 235000012239 silicon dioxide Nutrition 0.000 description 9
- 229910052682 stishovite Inorganic materials 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- 229910052905 tridymite Inorganic materials 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- WJYHCYBNUJVCEH-UHFFFAOYSA-N cyclohexane;ethoxyethane Chemical compound CCOCC.C1CCCCC1 WJYHCYBNUJVCEH-UHFFFAOYSA-N 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 239000007832 Na2SO4 Substances 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 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
- 239000000556 agonist Substances 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 229910052710 silicon Inorganic materials 0.000 description 6
- 239000010703 silicon Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical compound ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 5
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 208000021070 secondary pulmonary alveolar proteinosis Diseases 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- JADDQZYHOWSFJD-FLNNQWSLSA-N N-ethyl-5'-carboxamidoadenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 JADDQZYHOWSFJD-FLNNQWSLSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 230000003243 anti-lipolytic effect Effects 0.000 description 4
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 208000028867 ischemia Diseases 0.000 description 4
- 229940098779 methanesulfonic acid Drugs 0.000 description 4
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/167—Purine radicals with ribosyl as the saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
-
- 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
-
- 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
-
- 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
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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
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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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9723566.7A GB9723566D0 (en) | 1997-11-08 | 1997-11-08 | Chemical compounds |
| PCT/EP1998/007022 WO1999024450A2 (fr) | 1997-11-08 | 1998-11-06 | Composes chimiques |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20000276A2 true HRP20000276A2 (en) | 2000-12-31 |
Family
ID=10821742
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20000276A HRP20000276A2 (en) | 1997-11-08 | 2000-05-08 | Chemical compounds |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US6407076B1 (fr) |
| EP (1) | EP1027363B1 (fr) |
| JP (1) | JP2001522858A (fr) |
| KR (1) | KR20010031883A (fr) |
| CN (1) | CN1285842A (fr) |
| AP (1) | AP2000001803A0 (fr) |
| AT (1) | ATE242259T1 (fr) |
| AU (1) | AU1232799A (fr) |
| BR (1) | BR9813973A (fr) |
| CA (1) | CA2309199A1 (fr) |
| DE (1) | DE69815378T2 (fr) |
| EA (1) | EA200000393A1 (fr) |
| EE (1) | EE200000284A (fr) |
| ES (1) | ES2201552T3 (fr) |
| GB (1) | GB9723566D0 (fr) |
| HR (1) | HRP20000276A2 (fr) |
| HU (1) | HUP0004106A2 (fr) |
| IL (1) | IL135965A0 (fr) |
| IS (1) | IS5478A (fr) |
| NO (1) | NO20002360L (fr) |
| PL (1) | PL341091A1 (fr) |
| SK (1) | SK6712000A3 (fr) |
| TR (1) | TR200002157T2 (fr) |
| WO (1) | WO1999024450A2 (fr) |
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| AU4138601A (en) * | 1999-12-03 | 2001-06-12 | Cv Therapeutics, Inc. | Method of identifying partial adenosine a1 receptor agonists and their use in the treatment of arrhythmias |
| US6294522B1 (en) * | 1999-12-03 | 2001-09-25 | Cv Therapeutics, Inc. | N6 heterocyclic 8-modified adenosine derivatives |
| US6258793B1 (en) * | 1999-12-03 | 2001-07-10 | Cv Therapeutics, Inc. | N6 heterocyclic 5′ modified adenosine derivatives |
| US6605597B1 (en) * | 1999-12-03 | 2003-08-12 | Cv Therapeutics, Inc. | Partial or full A1agonists-N-6 heterocyclic 5′-thio substituted adenosine derivatives |
| GB9930077D0 (en) * | 1999-12-20 | 2000-02-09 | Glaxo Group Ltd | Medicaments |
| CA2414623A1 (fr) * | 2000-08-01 | 2002-02-07 | University Of Virginia Patent Foundation | Utilisation d'agonistes, d'antagonistes et d'amplificateurs allosteriques selectifs du recepteur d'adenosine a1 afin de manipuler l'angiogenese |
| GB2372742A (en) * | 2001-03-03 | 2002-09-04 | Univ Leiden | C2,5'-Disubstituted and N6,C2,5'-trisubstituted adenosine derivatives and their different uses |
| GB2372741A (en) * | 2001-03-03 | 2002-09-04 | Univ Leiden | C2,8-Disubstituted adenosine derivatives and their different uses |
| GB0106867D0 (en) * | 2001-03-20 | 2001-05-09 | Glaxo Group Ltd | Process |
| US6995148B2 (en) * | 2001-04-05 | 2006-02-07 | University Of Pittsburgh | Adenosine cyclic ketals: novel adenosine analogues for pharmacotherapy |
| US6946449B2 (en) | 2001-07-13 | 2005-09-20 | Cv Therapeutics, Inc. | Partial and full agonists of A1 adenosine receptors |
| US7157440B2 (en) | 2001-07-13 | 2007-01-02 | Cv Therapeutics, Inc. | Partial and full agonists of A1 adenosine receptors |
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| CA2460911C (fr) | 2001-10-01 | 2011-08-30 | University Of Virginia Patent Foundation | Analogues de 2-propynyle adenosine presentant une activite agoniste de a2a et compositions en contenant |
| ATE381336T1 (de) * | 2002-04-10 | 2008-01-15 | Univ Virginia | Verwendung von a2a adenosin rezeptor agonisten und anti-pathogene mittel enthaltenden kombinationen zur behandlung von entzündungskrankheiten |
| US7265111B2 (en) * | 2002-06-27 | 2007-09-04 | Sanofi-Aventis Deutschland Gmbh | Adenosine analogues and their use as pharmaceutical agents |
| EP1375508A1 (fr) * | 2002-06-27 | 2004-01-02 | Aventis Pharma Deutschland GmbH | Dérivés de l'adénosine N6-substitués et leur utilisation comme médicament |
| NZ541651A (en) | 2003-02-03 | 2009-01-31 | Cv Therapeutics Inc | Partial and full agonists of A1 adenosine receptors |
| AR044519A1 (es) | 2003-05-02 | 2005-09-14 | Novartis Ag | Derivados de piridin-tiazol amina y de pirimidin-tiazol amina |
| GB0401334D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
| US20050277615A1 (en) * | 2004-05-17 | 2005-12-15 | Can-Fite Biopharma Ltd. | Pharmaceutical compositions having anti-inflammatory activity |
| GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
| US7605143B2 (en) * | 2004-08-02 | 2009-10-20 | University Of Virginia Patent Foundation | 2-propynyl adenosine analogs with modified 5′-ribose groups having A2A agonist activity |
| WO2006028618A1 (fr) * | 2004-08-02 | 2006-03-16 | University Of Virginia Patent Foundation | Analogues d'adenosine de propynyle 2-polycyclique presentant des groupes 5'-ribose modifies presentant une activite agoniste de a2a |
| GB0424284D0 (en) | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
| GB0426164D0 (en) | 2004-11-29 | 2004-12-29 | Novartis Ag | Organic compounds |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| KR20080049113A (ko) | 2005-10-21 | 2008-06-03 | 노파르티스 아게 | Ｉｌ-13에 대항한 인간 항체 및 치료적 용도 |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| WO2007120972A2 (fr) * | 2006-02-10 | 2007-10-25 | University Of Virginia Patent Foundation | Procede permettant de traiter l'anemie a hematies falciformes |
| US8188063B2 (en) * | 2006-06-19 | 2012-05-29 | University Of Virginia Patent Foundation | Use of adenosine A2A modulators to treat spinal cord injury |
| ATE502943T1 (de) | 2006-09-29 | 2011-04-15 | Novartis Ag | Pyrazolopyrimidine als pi3k-lipidkinasehemmer |
| RU2009120389A (ru) | 2006-10-30 | 2010-12-10 | Новартис АГ (CH) | Гетероциклические соединения в качестве противовоспалительных агентов |
| US8058259B2 (en) * | 2007-12-20 | 2011-11-15 | University Of Virginia Patent Foundation | Substituted 4-{3-[6-amino-9-(3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-piperidine-1-carboxylic acid esters as A2AR agonists |
| WO2009087224A1 (fr) | 2008-01-11 | 2009-07-16 | Novartis Ag | Pyrimidines utilisés en tant qu'inhibiteurs de kinase |
| SI2391366T1 (sl) | 2009-01-29 | 2013-01-31 | Novartis Ag | Substituirani benzimidazoli za zdravljenje astrocitomov |
| US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
| CA2770873A1 (fr) | 2009-08-12 | 2011-02-17 | Novartis Ag | Composes hydrazone heterocycliques et leurs utilisations pour traiter le cancer et l'inflammation |
| SG178454A1 (en) | 2009-08-17 | 2012-03-29 | Intellikine Inc | Heterocyclic compounds and uses thereof |
| IN2012DN01453A (fr) | 2009-08-20 | 2015-06-05 | Novartis Ag | |
| CN102711771B (zh) | 2010-01-11 | 2016-05-18 | 伊诺泰克制药公司 | 降低眼压的组合、试剂盒和方法 |
| MX2012008961A (es) * | 2010-02-03 | 2013-04-29 | Meh Associates Inc | Fluorometanos multiples sustituidos como isosteros selectivos y bioactivos. |
| CN102933593A (zh) | 2010-03-26 | 2013-02-13 | 伊诺泰克制药公司 | 使用n6-环戊基腺苷（cpa）、cpa衍生物或其前药降低人眼内压的方法 |
| US8637516B2 (en) | 2010-09-09 | 2014-01-28 | Irm Llc | Compounds and compositions as TRK inhibitors |
| WO2012034095A1 (fr) | 2010-09-09 | 2012-03-15 | Irm Llc | Composés et compositions comme inhibiteurs de trk |
| US20130324526A1 (en) | 2011-02-10 | 2013-12-05 | Novartis Ag | [1,2,4] triazolo [4,3-b] pyridazine compounds as inhibitors of the c-met tyrosine kinase |
| JP5808826B2 (ja) | 2011-02-23 | 2015-11-10 | インテリカイン， エルエルシー | 複素環化合物およびその使用 |
| MA34969B1 (fr) | 2011-02-25 | 2014-03-01 | Irm Llc | Composes et compositions en tant qu inibiteurs de trk |
| CA2848809A1 (fr) | 2011-09-15 | 2013-03-21 | Novartis Ag | 3-(quinolin-6-ylthio)-[1,2,4]triazolo[4,3-a]pyradines substituees en position 6 a activite tyrosine kinase |
| CA2856803A1 (fr) | 2011-11-23 | 2013-05-30 | Intellikine, Llc | Regimes de traitement ameliores utilisant des inhibiteurs de mtor |
| EA027109B1 (ru) | 2012-01-26 | 2017-06-30 | Инотек Фармасьютикалс Корпорейшн | Безводные полиморфы [(2r,3s,4r,5r)-5-(6-(циклопентиламино)-9h-пурин-9-ил)-3,4-дигидрокситетрагидрофуран-2-ил]метилнитрата и способы их получения |
| EP3964513A1 (fr) | 2012-04-03 | 2022-03-09 | Novartis AG | Produits combinés comprenant des inhibiteurs de tyrosine kinase et leur utilisation |
| MX2015013234A (es) | 2013-03-15 | 2016-04-15 | Inotek Pharmaceuticals Corp | Formulaciones oftalmicas. |
| WO2014151147A1 (fr) | 2013-03-15 | 2014-09-25 | Intellikine, Llc | Combinaison d'inhibiteurs de kinase et ses utilisations |
| TW201605450A (zh) | 2013-12-03 | 2016-02-16 | 諾華公司 | Ｍｄｍ２抑制劑與ＢＲＡＦ抑制劑之組合及其用途 |
| WO2016011658A1 (fr) | 2014-07-25 | 2016-01-28 | Novartis Ag | Polythérapie |
| AU2015294889B2 (en) | 2014-07-31 | 2018-03-15 | Novartis Ag | Combination therapy |
| TW202140550A (zh) | 2020-01-29 | 2021-11-01 | 瑞士商諾華公司 | 使用抗ｔｓｌｐ抗體治療炎性或阻塞性氣道疾病之方法 |
| CN116554194A (zh) * | 2023-05-23 | 2023-08-08 | 江苏八巨药业有限公司 | 一种卡培他滨中间体的合成方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO1988003147A1 (fr) * | 1986-10-31 | 1988-05-05 | Warner-Lambert Company | Adenosines a substitution n6 selectionees ayant une activite de liaison a2 selective |
| US5561134A (en) | 1990-09-25 | 1996-10-01 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Compounds having antihypertensive, cardioprotective, anti-ischemic and antilipolytic properties |
| US5652366A (en) * | 1990-09-25 | 1997-07-29 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | DI (1R)-(-)camphosulfonic acid) salt, preparation thereof and use thereof |
| WO1997033591A1 (fr) * | 1996-03-13 | 1997-09-18 | Novo Nordisk A/S | Procede de traitement d'affections associees aux cytokines chez les mammiferes |
| GB9610031D0 (en) * | 1996-05-14 | 1996-07-17 | Glaxo Group Ltd | Chemical compounds |
| US6232297B1 (en) * | 1999-02-01 | 2001-05-15 | University Of Virginia Patent Foundation | Methods and compositions for treating inflammatory response |
-
1997
- 1997-11-08 GB GBGB9723566.7A patent/GB9723566D0/en not_active Ceased
-
1998
- 1998-11-06 PL PL98341091A patent/PL341091A1/xx unknown
- 1998-11-06 EE EEP200000284A patent/EE200000284A/xx unknown
- 1998-11-06 EP EP98955538A patent/EP1027363B1/fr not_active Expired - Lifetime
- 1998-11-06 KR KR1020007004974A patent/KR20010031883A/ko not_active Application Discontinuation
- 1998-11-06 BR BR9813973-8A patent/BR9813973A/pt not_active Application Discontinuation
- 1998-11-06 IL IL13596598A patent/IL135965A0/xx unknown
- 1998-11-06 CN CN98812978A patent/CN1285842A/zh active Pending
- 1998-11-06 SK SK671-2000A patent/SK6712000A3/sk unknown
- 1998-11-06 TR TR2000/02157T patent/TR200002157T2/xx unknown
- 1998-11-06 AT AT98955538T patent/ATE242259T1/de not_active IP Right Cessation
- 1998-11-06 AP APAP/P/2000/001803A patent/AP2000001803A0/en unknown
- 1998-11-06 WO PCT/EP1998/007022 patent/WO1999024450A2/fr not_active Application Discontinuation
- 1998-11-06 US US09/530,574 patent/US6407076B1/en not_active Expired - Fee Related
- 1998-11-06 DE DE69815378T patent/DE69815378T2/de not_active Expired - Fee Related
- 1998-11-06 EA EA200000393A patent/EA200000393A1/ru unknown
- 1998-11-06 CA CA002309199A patent/CA2309199A1/fr not_active Abandoned
- 1998-11-06 HU HU0004106A patent/HUP0004106A2/hu unknown
- 1998-11-06 AU AU12327/99A patent/AU1232799A/en not_active Abandoned
- 1998-11-06 JP JP2000520458A patent/JP2001522858A/ja active Pending
- 1998-11-06 ES ES98955538T patent/ES2201552T3/es not_active Expired - Lifetime
-
2000
- 2000-05-03 IS IS5478A patent/IS5478A/is unknown
- 2000-05-05 NO NO20002360A patent/NO20002360L/no not_active Application Discontinuation
- 2000-05-08 HR HR20000276A patent/HRP20000276A2/hr not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0004106A2 (hu) | 2001-04-28 |
| NO20002360L (no) | 2000-07-05 |
| BR9813973A (pt) | 2000-09-26 |
| CN1285842A (zh) | 2001-02-28 |
| JP2001522858A (ja) | 2001-11-20 |
| IL135965A0 (en) | 2001-05-20 |
| GB9723566D0 (en) | 1998-01-07 |
| EP1027363B1 (fr) | 2003-06-04 |
| SK6712000A3 (en) | 2001-01-18 |
| AP2000001803A0 (en) | 2000-06-30 |
| US6407076B1 (en) | 2002-06-18 |
| EE200000284A (et) | 2001-08-15 |
| ATE242259T1 (de) | 2003-06-15 |
| IS5478A (is) | 2000-05-03 |
| PL341091A1 (en) | 2001-03-26 |
| EA200000393A1 (ru) | 2000-12-25 |
| WO1999024450A3 (fr) | 1999-08-19 |
| WO1999024450A2 (fr) | 1999-05-20 |
| DE69815378D1 (de) | 2003-07-10 |
| DE69815378T2 (de) | 2004-04-29 |
| ES2201552T3 (es) | 2004-03-16 |
| NO20002360D0 (no) | 2000-05-05 |
| CA2309199A1 (fr) | 1999-05-20 |
| KR20010031883A (ko) | 2001-04-16 |
| TR200002157T2 (tr) | 2000-11-21 |
| AU1232799A (en) | 1999-05-31 |
| EP1027363A2 (fr) | 2000-08-16 |
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