PL214682B1 - Tienopirymidynodiony, sposób ich wytwarzania oraz zawierajacy je srodek farmaceutyczny - Google Patents
Tienopirymidynodiony, sposób ich wytwarzania oraz zawierajacy je srodek farmaceutycznyInfo
- Publication number
- PL214682B1 PL214682B1 PL378222A PL37822204A PL214682B1 PL 214682 B1 PL214682 B1 PL 214682B1 PL 378222 A PL378222 A PL 378222A PL 37822204 A PL37822204 A PL 37822204A PL 214682 B1 PL214682 B1 PL 214682B1
- Authority
- PL
- Poland
- Prior art keywords
- methyl
- carbonyl
- methylethyl
- pyrimidine
- tetrahydro
- Prior art date
Links
- 208000023275 Autoimmune disease Diseases 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 166
- 238000000034 method Methods 0.000 claims abstract description 42
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 230000008569 process Effects 0.000 claims abstract description 5
- -1 quinoyl Chemical group 0.000 claims description 108
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 89
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 68
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 65
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 41
- 230000002829 reductive effect Effects 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 33
- 229910052757 nitrogen Inorganic materials 0.000 claims description 29
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- JGOOQALRLGHKIY-UHFFFAOYSA-N 1h-thieno[2,3-d]pyrimidine-2,4-dione Chemical compound O=C1NC(=O)NC2=C1C=CS2 JGOOQALRLGHKIY-UHFFFAOYSA-N 0.000 claims description 17
- QAFVXBQPQCSSLI-UHFFFAOYSA-N 1h-thieno[3,2-d]pyrimidine-2,4-dione Chemical compound O=C1NC(=O)NC2=C1SC=C2 QAFVXBQPQCSSLI-UHFFFAOYSA-N 0.000 claims description 17
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 16
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000006413 ring segment Chemical group 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 239000000010 aprotic solvent Substances 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 239000012442 inert solvent Substances 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 125000004122 cyclic group Chemical group 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- NMHRECIQUFFUHV-NRFANRHFSA-N 1-cyclopropyl-6-[(3,5-dimethyl-1h-pyrazol-4-yl)methyl]-5-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound CC1=NNC(C)=C1CC1=C(C(=O)N2OC[C@@](C)(O)C2)C(C(=O)N(C)C(=O)N2C3CC3)=C2S1 NMHRECIQUFFUHV-NRFANRHFSA-N 0.000 claims description 4
- XWIYUCRMWCHYJR-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine Chemical compound C1=CC=C2NC=CC2=N1 XWIYUCRMWCHYJR-UHFFFAOYSA-N 0.000 claims description 4
- PRNXOFBDXNTIFG-HXUWFJFHSA-N 5-[(4r)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-6-[[5-methyl-3-(trifluoromethyl)-1h-pyrazol-4-yl]methyl]-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C([C@](C)(O)C1)ON1C(=O)C=1C=2C(=O)N(C)C(=O)N(C(C)C)C=2SC=1CC1=C(C)NN=C1C(F)(F)F PRNXOFBDXNTIFG-HXUWFJFHSA-N 0.000 claims description 4
- YVFBMNCDAFQCEQ-QHCPKHFHSA-N 5-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-1-propan-2-yl-6-(1h-pyrrolo[2,3-b]pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(C(C)C)C=2SC(CC=2C3=CC=CN=C3NC=2)=C1C(=O)N1C[C@](C)(O)CO1 YVFBMNCDAFQCEQ-QHCPKHFHSA-N 0.000 claims description 4
- RYCSBKCBICNZBS-MHZLTWQESA-N 5-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-1-propan-2-yl-6-[(4-pyridin-2-ylphenyl)methyl]thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C([C@@](C)(O)C1)ON1C(=O)C=1C=2C(=O)N(C)C(=O)N(C(C)C)C=2SC=1CC(C=C1)=CC=C1C1=CC=CC=N1 RYCSBKCBICNZBS-MHZLTWQESA-N 0.000 claims description 4
- SPMGLYKATLKNRK-SANMLTNESA-N 5-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-1-propan-2-yl-6-[(4-pyrimidin-2-ylphenyl)methyl]thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C([C@@](C)(O)C1)ON1C(=O)C=1C=2C(=O)N(C)C(=O)N(C(C)C)C=2SC=1CC(C=C1)=CC=C1C1=NC=CC=N1 SPMGLYKATLKNRK-SANMLTNESA-N 0.000 claims description 4
- YIOZKLDAZRCZTF-VWLOTQADSA-N 5-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-6-[(1-phenylpyrazol-4-yl)methyl]-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C([C@@](C)(O)C1)ON1C(=O)C=1C=2C(=O)N(C)C(=O)N(C(C)C)C=2SC=1CC(=C1)C=NN1C1=CC=CC=C1 YIOZKLDAZRCZTF-VWLOTQADSA-N 0.000 claims description 4
- PRNXOFBDXNTIFG-FQEVSTJZSA-N 5-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-6-[[5-methyl-3-(trifluoromethyl)-1h-pyrazol-4-yl]methyl]-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C([C@@](C)(O)C1)ON1C(=O)C=1C=2C(=O)N(C)C(=O)N(C(C)C)C=2SC=1CC1=C(C)NN=C1C(F)(F)F PRNXOFBDXNTIFG-FQEVSTJZSA-N 0.000 claims description 4
- IXYCVRJQEKQPFU-VWLOTQADSA-N 6-[(8-fluoroquinolin-4-yl)methyl]-5-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(C(C)C)C=2SC(CC=2C3=CC=CC(F)=C3N=CC=2)=C1C(=O)N1C[C@](C)(O)CO1 IXYCVRJQEKQPFU-VWLOTQADSA-N 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- FKIUQMBRQLGLAC-QFIPXVFZSA-N 6-[(3,5-dimethyl-1h-pyrazol-4-yl)methyl]-5-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C([C@@](C)(O)C1)ON1C(=O)C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC=1C(C)=NNC=1C FKIUQMBRQLGLAC-QFIPXVFZSA-N 0.000 claims description 3
- KWSDOBIBNMXOEI-NRFANRHFSA-N 6-[(3,5-dimethyl-1h-pyrazol-4-yl)methyl]-5-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-1-propylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C([C@@](C)(O)C1)ON1C(=O)C=1C=2C(=O)N(C)C(=O)N(CCC)C=2SC=1CC=1C(C)=NNC=1C KWSDOBIBNMXOEI-NRFANRHFSA-N 0.000 claims description 3
- 238000010976 amide bond formation reaction Methods 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- HKEWOTUTAYJWQJ-UHFFFAOYSA-N 2-(1h-pyrazol-5-yl)pyridine Chemical compound N1N=CC=C1C1=CC=CC=N1 HKEWOTUTAYJWQJ-UHFFFAOYSA-N 0.000 claims description 2
- SOFSLARRWWWVMX-DEOSSOPVSA-N 5-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-6-[[5-methyl-1-pyrimidin-2-yl-3-(trifluoromethyl)pyrazol-4-yl]methyl]-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C([C@@](C)(O)C1)ON1C(=O)C=1C=2C(=O)N(C)C(=O)N(C(C)C)C=2SC=1CC(C(=N1)C(F)(F)F)=C(C)N1C1=NC=CC=N1 SOFSLARRWWWVMX-DEOSSOPVSA-N 0.000 claims description 2
- ORBWWPHPDXXVIW-FQEVSTJZSA-N 6-[(2,4-dichloro-1,3-thiazol-5-yl)methyl]-5-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C([C@@](C)(O)C1)ON1C(=O)C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC=1SC(Cl)=NC=1Cl ORBWWPHPDXXVIW-FQEVSTJZSA-N 0.000 claims description 2
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 claims description 2
- 239000012964 benzotriazole Substances 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims 3
- VNXZYGDWCBUEDR-VWLOTQADSA-N 5-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-1-propyl-6-(quinolin-4-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CCC)C=2SC(CC=2C3=CC=CC=C3N=CC=2)=C1C(=O)N1C[C@](C)(O)CO1 VNXZYGDWCBUEDR-VWLOTQADSA-N 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 abstract description 5
- 206010062016 Immunosuppression Diseases 0.000 abstract description 3
- 230000001506 immunosuppresive effect Effects 0.000 abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 173
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 143
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 118
- 239000000047 product Substances 0.000 description 87
- 239000000203 mixture Substances 0.000 description 80
- 238000004949 mass spectrometry Methods 0.000 description 68
- 239000000243 solution Substances 0.000 description 63
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 53
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- 239000007787 solid Substances 0.000 description 52
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
- 239000002253 acid Substances 0.000 description 48
- 235000019439 ethyl acetate Nutrition 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
- IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 description 31
- 239000011541 reaction mixture Substances 0.000 description 26
- 239000000377 silicon dioxide Substances 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 125000004494 ethyl ester group Chemical group 0.000 description 20
- 239000012299 nitrogen atmosphere Substances 0.000 description 20
- 239000000284 extract Substances 0.000 description 17
- 238000010992 reflux Methods 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000004587 chromatography analysis 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
- 238000004440 column chromatography Methods 0.000 description 14
- 239000000725 suspension Substances 0.000 description 13
- 239000002585 base Substances 0.000 description 12
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 206010039083 rhinitis Diseases 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
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- 208000006673 asthma Diseases 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical group ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 8
- 125000005997 bromomethyl group Chemical group 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 7
- OLNLDUFKOYOGAA-UHFFFAOYSA-N thieno[2,3-d]pyrimidine-5-carboxylic acid Chemical compound C1=NC=C2C(C(=O)O)=CSC2=N1 OLNLDUFKOYOGAA-UHFFFAOYSA-N 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 150000004702 methyl esters Chemical class 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 6
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 239000006260 foam Substances 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- XMVNUAHPLDBEJH-UHFFFAOYSA-N methyl pyrimidine-5-carboxylate Chemical compound COC(=O)C1=CN=CN=C1 XMVNUAHPLDBEJH-UHFFFAOYSA-N 0.000 description 5
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
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- 230000004054 inflammatory process Effects 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
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- 201000010659 intrinsic asthma Diseases 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- NQXWGWZJXJUMQB-UHFFFAOYSA-K iron trichloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].Cl[Fe+]Cl NQXWGWZJXJUMQB-UHFFFAOYSA-K 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- DEXFPBDHIIHRQJ-UHFFFAOYSA-N methyl 1-cyclopropyl-3,6-dimethyl-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxylate Chemical compound COC(=O)C1=C(SC=2N(C(N(C(C=21)=O)C)=O)C1CC1)C DEXFPBDHIIHRQJ-UHFFFAOYSA-N 0.000 description 1
- ZKEUZEKFHWSORU-UHFFFAOYSA-N methyl 1-cyclopropyl-6-methyl-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxylate Chemical compound COC(=O)C1=C(SC=2N(C(NC(C=21)=O)=O)C1CC1)C ZKEUZEKFHWSORU-UHFFFAOYSA-N 0.000 description 1
- FNEQZEGPEDNVJO-AWEZNQCLSA-N methyl 2-[(4s)-4-ethyl-4-hydroxy-1,2-oxazolidine-2-carbonyl]benzoate Chemical compound C1[C@](CC)(O)CON1C(=O)C1=CC=CC=C1C(=O)OC FNEQZEGPEDNVJO-AWEZNQCLSA-N 0.000 description 1
- YNLMJEPXHLXGRQ-ZDUSSCGKSA-N methyl 2-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]benzoate Chemical compound COC(=O)C1=CC=CC=C1C(=O)N1OC[C@@](C)(O)C1 YNLMJEPXHLXGRQ-ZDUSSCGKSA-N 0.000 description 1
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- IHYNKGRWCDKNEG-UHFFFAOYSA-N n-(4-bromophenyl)-2,6-dihydroxybenzamide Chemical compound OC1=CC=CC(O)=C1C(=O)NC1=CC=C(Br)C=C1 IHYNKGRWCDKNEG-UHFFFAOYSA-N 0.000 description 1
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- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- NWELCUKYUCBVKK-UHFFFAOYSA-N pyridin-2-ylhydrazine Chemical compound NNC1=CC=CC=N1 NWELCUKYUCBVKK-UHFFFAOYSA-N 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
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- 210000002966 serum Anatomy 0.000 description 1
- DOQQTKLDEQSKIE-UHFFFAOYSA-N silver;isocyanate Chemical compound [Ag+].[N-]=C=O DOQQTKLDEQSKIE-UHFFFAOYSA-N 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
- JGWPCVMLCWDIIY-UHFFFAOYSA-M sodium 7,7-dioxothieno[2,3-d]pyrimidine-5-carboxylate Chemical compound C1=C2C(=CS(=O)(=O)C2=NC=N1)C(=O)[O-].[Na+] JGWPCVMLCWDIIY-UHFFFAOYSA-M 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
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- 238000007920 subcutaneous administration Methods 0.000 description 1
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- 150000003890 succinate salts Chemical class 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0300119A SE0300119D0 (sv) | 2003-01-17 | 2003-01-17 | Novel compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL378222A1 PL378222A1 (pl) | 2006-03-20 |
| PL214682B1 true PL214682B1 (pl) | 2013-09-30 |
Family
ID=20290154
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| PL378222A PL214682B1 (pl) | 2003-01-17 | 2004-01-15 | Tienopirymidynodiony, sposób ich wytwarzania oraz zawierajacy je srodek farmaceutyczny |
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| JP (1) | JP4519121B2 (enExample) |
| KR (2) | KR20110125256A (enExample) |
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| AT (1) | ATE335748T1 (enExample) |
| AU (1) | AU2004206012B2 (enExample) |
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| CA (1) | CA2512441C (enExample) |
| DE (1) | DE602004001857T2 (enExample) |
| EG (1) | EG25613A (enExample) |
| ES (1) | ES2270337T3 (enExample) |
| IL (1) | IL169370A (enExample) |
| IS (1) | IS2376B (enExample) |
| MX (1) | MXPA05007496A (enExample) |
| NO (1) | NO333702B1 (enExample) |
| NZ (1) | NZ541217A (enExample) |
| PL (1) | PL214682B1 (enExample) |
| RU (1) | RU2331647C2 (enExample) |
| SE (1) | SE0300119D0 (enExample) |
| UA (1) | UA81788C2 (enExample) |
| WO (1) | WO2004065394A1 (enExample) |
| ZA (1) | ZA200505364B (enExample) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
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| GB0117583D0 (en) * | 2001-07-19 | 2001-09-12 | Astrazeneca Ab | Novel compounds |
| GB0118479D0 (en) * | 2001-07-28 | 2001-09-19 | Astrazeneca Ab | Novel compounds |
| JP2006515880A (ja) * | 2003-01-17 | 2006-06-08 | アストラゼネカ・アクチエボラーグ | 自己免疫疾患の調節におけるチエノピリダジノンとその使用 |
| SE0300120D0 (sv) * | 2003-01-17 | 2003-01-17 | Astrazeneca Ab | Novel compounds |
| US7504509B2 (en) | 2003-12-19 | 2009-03-17 | Plexxikon, Inc. | Compounds and methods for development of Ret modulators |
| US7498342B2 (en) | 2004-06-17 | 2009-03-03 | Plexxikon, Inc. | Compounds modulating c-kit activity |
| WO2007013896A2 (en) | 2005-05-17 | 2007-02-01 | Plexxikon, Inc. | Pyrrol (2,3-b) pyridine derivatives protein kinase inhibitors |
| TWI473808B (zh) | 2005-06-22 | 2015-02-21 | Plexxikon Inc | 用於激酶調節的化合物及方法及其適應症 |
| WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
| PE20121126A1 (es) | 2006-12-21 | 2012-08-24 | Plexxikon Inc | Compuestos pirrolo [2,3-b] piridinas como moduladores de quinasa |
| JP2010514695A (ja) | 2006-12-21 | 2010-05-06 | プレキシコン，インコーポレーテッド | キナーゼ調節のための化合物および方法およびそのための適応症 |
| WO2008079909A1 (en) | 2006-12-21 | 2008-07-03 | Plexxikon, Inc. | Pyrrolo [2,3-b] pyridines as kinase modulators |
| GB0713479D0 (en) * | 2007-07-11 | 2007-08-22 | Syngenta Participations Ag | Substituted aromatic heterocyclic compounds as fungicides |
| SG183036A1 (en) | 2007-07-17 | 2012-08-30 | Plexxikon Inc | Compounds and methods for kinase modulation, and indications therefor |
| WO2010089580A1 (en) | 2009-02-06 | 2010-08-12 | Astrazeneca Ab | Use of a mct1 inhibitor in the treatment of cancers expressing mct1 over mct4 |
| SG184766A1 (en) * | 2009-03-23 | 2012-10-30 | Glenmark Pharmaceuticals Sa | Isothiazolo-pyrimidinedione derivatives as trpa1 modulators |
| CN102361874A (zh) * | 2009-03-23 | 2012-02-22 | 格兰马克药品股份有限公司 | 作为trpa1调节剂的呋喃并嘧啶二酮衍生物 |
| AU2010232670B2 (en) | 2009-04-03 | 2015-07-09 | F. Hoffmann-La Roche Ag | Propane- I-sulfonic acid {3- [5- (4 -chloro-phenyl) -1H-pyrrolo [2, 3-b] pyridine-3-carbonyl] -2, 4-difluoro-pheny l } -amide compositions and uses thereof |
| US8329724B2 (en) | 2009-08-03 | 2012-12-11 | Hoffmann-La Roche Inc. | Process for the manufacture of pharmaceutically active compounds |
| MX2012005284A (es) | 2009-11-06 | 2012-06-28 | Plexxikon Inc | Compuestos y metodos para la modulacion de cinasas. e indicaciones para ello. |
| KR101911972B1 (ko) | 2011-02-07 | 2018-10-25 | 플렉시콘 인코퍼레이티드 | 키나제 조절을 위한 화합물 및 방법, 및 그에 대한 적응증 |
| TWI558702B (zh) | 2011-02-21 | 2016-11-21 | 普雷辛肯公司 | 醫藥活性物質的固態形式 |
| EP2804852A2 (en) | 2012-01-20 | 2014-11-26 | Regents Of The University Of Minnesota | Therapeutic compounds |
| US10085987B2 (en) | 2012-01-27 | 2018-10-02 | Thomas Jefferson University | MCT protein inhibitor-related prognostic and therapeutic methods |
| US9150570B2 (en) | 2012-05-31 | 2015-10-06 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
| US10022372B2 (en) | 2013-04-19 | 2018-07-17 | Thomas Jefferson University | Caveolin-1 related methods for treating glioblastoma with temozolomide |
| PT3060562T (pt) * | 2013-10-21 | 2021-09-02 | Genosco | Compostos de pirimidina substituídos e sua utilização como inibidores da syk |
| US10329303B2 (en) | 2015-01-22 | 2019-06-25 | The Scripps Research Institute | Heterocyclic inhibitors of monocarboxylate transporter |
| UY36586A (es) * | 2015-03-26 | 2016-10-31 | Bayer Pharma AG | Heterociclilmetiltienouracilos y uso de los mismos |
| KR101730536B1 (ko) * | 2016-03-17 | 2017-05-02 | 주식회사 골프존 | 스크린 골프 시스템에서 구현되는 컨텐츠 전송 서비스 방법, 컨텐츠 전송 서비스를 위한 모바일 단말기의 제어방법 및 이를 기록한 컴퓨팅 장치에 의해 판독 가능한 기록매체 |
| KR101712836B1 (ko) * | 2016-03-17 | 2017-03-22 | 주식회사 골프존 | 가상 골프 시뮬레이션 장치, 가상 골프를 위한 영상 구현 방법 및 이를 기록한 컴퓨팅 장치에 의해 판독 가능한 기록 매체 |
| KR101712838B1 (ko) * | 2016-03-17 | 2017-03-07 | 주식회사 골프존 | 가상 골프 시뮬레이션 장치, 가상 골프를 위한 영상 구현 방법 및 이를 기록한 컴퓨팅 장치에 의해 판독 가능한 기록 매체 |
| TWI823932B (zh) * | 2018-05-11 | 2023-12-01 | 中國大陸商迪哲（江蘇）醫藥有限公司 | 三唑并嘧啶化合物及其在治療癌症中之用途 |
| CN119080799B (zh) * | 2024-09-27 | 2025-12-05 | 山东大学 | 一种n-羟基噻吩并嘧啶二酮类衍生物及其制备方法与应用 |
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| US738495A (en) * | 1902-12-26 | 1903-09-08 | William E Sherwood | Thill-coupling. |
| SE9702001D0 (sv) * | 1997-05-28 | 1997-05-28 | Astra Pharma Prod | Novel compounds |
| US6469014B1 (en) * | 1997-05-28 | 2002-10-22 | Astrazeneca Ab | Thieno[2,3-d] pyrimidinediones, their preparation and use in therapy |
| JP2001525413A (ja) | 1997-12-05 | 2001-12-11 | アストラゼネカ ユーケイ リミテッド | 新規化合物 |
| US6232320B1 (en) | 1998-06-04 | 2001-05-15 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| ES2211161T3 (es) * | 1998-08-28 | 2004-07-01 | Astrazeneca Ab | Tieno(2,3-d)pirimidindionas novedosas, procedimiento para su preparacion y uso de las mismas en terapia. |
| WO2001083489A1 (en) * | 2000-05-04 | 2001-11-08 | Astrazeneca Ab | THIENO[2,3-d]PYRIMIDINEDIONES AND THEIR USE AS PHARMACEUTICALS |
| GB0117583D0 (en) * | 2001-07-19 | 2001-09-12 | Astrazeneca Ab | Novel compounds |
| GB0118479D0 (en) | 2001-07-28 | 2001-09-19 | Astrazeneca Ab | Novel compounds |
| SE0300120D0 (sv) | 2003-01-17 | 2003-01-17 | Astrazeneca Ab | Novel compounds |
| JP2006515880A (ja) | 2003-01-17 | 2006-06-08 | アストラゼネカ・アクチエボラーグ | 自己免疫疾患の調節におけるチエノピリダジノンとその使用 |
-
2003
- 2003-01-17 SE SE0300119A patent/SE0300119D0/xx unknown
-
2004
- 2004-01-15 US US10/542,197 patent/US7384951B2/en not_active Expired - Lifetime
- 2004-01-15 ES ES04702477T patent/ES2270337T3/es not_active Expired - Lifetime
- 2004-01-15 EP EP04702477A patent/EP1587812B1/en not_active Expired - Lifetime
- 2004-01-15 CA CA2512441A patent/CA2512441C/en not_active Expired - Lifetime
- 2004-01-15 UA UAA200506377A patent/UA81788C2/uk unknown
- 2004-01-15 JP JP2006500750A patent/JP4519121B2/ja not_active Expired - Fee Related
- 2004-01-15 AU AU2004206012A patent/AU2004206012B2/en not_active Ceased
- 2004-01-15 NZ NZ541217A patent/NZ541217A/en not_active IP Right Cessation
- 2004-01-15 MX MXPA05007496A patent/MXPA05007496A/es active IP Right Grant
- 2004-01-15 PL PL378222A patent/PL214682B1/pl unknown
- 2004-01-15 KR KR1020117022785A patent/KR20110125256A/ko not_active Withdrawn
- 2004-01-15 DE DE602004001857T patent/DE602004001857T2/de not_active Expired - Lifetime
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- 2004-01-15 CN CNB2004800071073A patent/CN100334093C/zh not_active Expired - Fee Related
- 2004-01-15 WO PCT/SE2004/000052 patent/WO2004065394A1/en not_active Ceased
- 2004-01-15 KR KR1020057013126A patent/KR101107486B1/ko not_active Expired - Fee Related
- 2004-01-15 RU RU2005121494/04A patent/RU2331647C2/ru not_active IP Right Cessation
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2005
- 2005-06-23 IL IL169370A patent/IL169370A/en active IP Right Grant
- 2005-07-01 ZA ZA2005/05364A patent/ZA200505364B/en unknown
- 2005-07-12 EG EGNA2005000380 patent/EG25613A/xx active
- 2005-07-29 IS IS7965A patent/IS2376B/is unknown
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2008
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