HRP20020096A2 - Interleukin-5 inhibiting 6-azauracil derivatives - Google Patents
Interleukin-5 inhibiting 6-azauracil derivativesInfo
- Publication number
- HRP20020096A2 HRP20020096A2 HR20020096A HRP20020096A HRP20020096A2 HR P20020096 A2 HRP20020096 A2 HR P20020096A2 HR 20020096 A HR20020096 A HR 20020096A HR P20020096 A HRP20020096 A HR P20020096A HR P20020096 A2 HRP20020096 A2 HR P20020096A2
- Authority
- HR
- Croatia
- Prior art keywords
- alkyl
- substituted
- hydroxy
- cycloalkyl
- formula
- Prior art date
Links
- SSPYSWLZOPCOLO-UHFFFAOYSA-N 6-azauracil Chemical class O=C1C=NNC(=O)N1 SSPYSWLZOPCOLO-UHFFFAOYSA-N 0.000 title claims description 20
- 108010002616 Interleukin-5 Proteins 0.000 title description 14
- 102000000743 Interleukin-5 Human genes 0.000 title description 14
- 229940100602 interleukin-5 Drugs 0.000 title description 11
- 230000002401 inhibitory effect Effects 0.000 title description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 311
- -1 NR 5 Inorganic materials 0.000 claims description 302
- 150000001875 compounds Chemical class 0.000 claims description 252
- 239000000203 mixture Substances 0.000 claims description 239
- 125000001424 substituent group Chemical group 0.000 claims description 143
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 99
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 99
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 96
- 229910052739 hydrogen Inorganic materials 0.000 claims description 92
- 239000001257 hydrogen Substances 0.000 claims description 92
- 125000003118 aryl group Chemical group 0.000 claims description 77
- 150000002431 hydrogen Chemical group 0.000 claims description 68
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 58
- 125000005843 halogen group Chemical group 0.000 claims description 53
- 125000000623 heterocyclic group Chemical group 0.000 claims description 52
- 125000004076 pyridyl group Chemical group 0.000 claims description 47
- 229910052757 nitrogen Inorganic materials 0.000 claims description 46
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 45
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 43
- 125000000335 thiazolyl group Chemical group 0.000 claims description 43
- 125000004432 carbon atom Chemical group C* 0.000 claims description 42
- 229910052760 oxygen Inorganic materials 0.000 claims description 42
- 229910052717 sulfur Inorganic materials 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 40
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 37
- 125000002883 imidazolyl group Chemical group 0.000 claims description 37
- 125000003386 piperidinyl group Chemical group 0.000 claims description 36
- 125000001544 thienyl group Chemical group 0.000 claims description 35
- 125000002541 furyl group Chemical group 0.000 claims description 32
- 125000001425 triazolyl group Chemical group 0.000 claims description 31
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 30
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 30
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 30
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 29
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 29
- 125000002971 oxazolyl group Chemical group 0.000 claims description 29
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 29
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 29
- 229910052799 carbon Inorganic materials 0.000 claims description 28
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 28
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 27
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 25
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 24
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 24
- 125000004306 triazinyl group Chemical group 0.000 claims description 24
- 125000004193 piperazinyl group Chemical group 0.000 claims description 23
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 238000002360 preparation method Methods 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 19
- 125000002757 morpholinyl group Chemical group 0.000 claims description 19
- 125000005879 dioxolanyl group Chemical group 0.000 claims description 18
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
- 125000002755 pyrazolinyl group Chemical group 0.000 claims description 18
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 16
- 125000004104 aryloxy group Chemical group 0.000 claims description 16
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 16
- 210000003979 eosinophil Anatomy 0.000 claims description 16
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 16
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 16
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 16
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 16
- 125000005493 quinolyl group Chemical group 0.000 claims description 16
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 16
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 16
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 16
- 125000001166 thiolanyl group Chemical group 0.000 claims description 16
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 16
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
- 125000005968 oxazolinyl group Chemical group 0.000 claims description 15
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 14
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 13
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 13
- 125000000532 dioxanyl group Chemical group 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 13
- 125000001041 indolyl group Chemical group 0.000 claims description 13
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 claims description 13
- 125000005990 isobenzothienyl group Chemical group 0.000 claims description 13
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 13
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 239000002585 base Substances 0.000 claims description 12
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 12
- 125000005883 dithianyl group Chemical group 0.000 claims description 12
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 12
- 230000000670 limiting effect Effects 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 229910052698 phosphorus Inorganic materials 0.000 claims description 12
- 239000011574 phosphorus Substances 0.000 claims description 12
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 12
- 239000011593 sulfur Substances 0.000 claims description 12
- 125000005455 trithianyl group Chemical group 0.000 claims description 12
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 11
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 11
- 229920006395 saturated elastomer Polymers 0.000 claims description 11
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 10
- 125000005947 C1-C6 alkylsulfonyloxy group Chemical group 0.000 claims description 10
- 125000004682 aminothiocarbonyl group Chemical group NC(=S)* 0.000 claims description 10
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
- 229910052702 rhenium Inorganic materials 0.000 claims description 10
- 125000005110 aryl thio group Chemical group 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 208000027866 inflammatory disease Diseases 0.000 claims description 8
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 8
- 230000001419 dependent effect Effects 0.000 claims description 7
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 7
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 6
- 150000001204 N-oxides Chemical class 0.000 claims description 6
- 101100070530 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) het-6 gene Proteins 0.000 claims description 6
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 239000012442 inert solvent Substances 0.000 claims description 6
- 125000004585 polycyclic heterocycle group Chemical group 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 229910052703 rhodium Inorganic materials 0.000 claims description 6
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 6
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 231100000252 nontoxic Toxicity 0.000 claims description 4
- 230000003000 nontoxic effect Effects 0.000 claims description 4
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 230000009466 transformation Effects 0.000 claims description 2
- BFGQTWYXWNCTSX-UHFFFAOYSA-N triazine-4,5-dione Chemical compound O=C1C=NN=NC1=O BFGQTWYXWNCTSX-UHFFFAOYSA-N 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 16
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 3
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 238000010306 acid treatment Methods 0.000 claims 1
- 230000008030 elimination Effects 0.000 claims 1
- 238000003379 elimination reaction Methods 0.000 claims 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims 1
- 238000000844 transformation Methods 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 423
- 239000002904 solvent Substances 0.000 description 265
- 239000002244 precipitate Substances 0.000 description 245
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 224
- 239000000543 intermediate Substances 0.000 description 195
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 174
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 159
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 158
- 229910001868 water Inorganic materials 0.000 description 138
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 118
- 239000003480 eluent Substances 0.000 description 113
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 110
- 239000012044 organic layer Substances 0.000 description 105
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 104
- 239000000741 silica gel Substances 0.000 description 100
- 229910002027 silica gel Inorganic materials 0.000 description 100
- 238000004440 column chromatography Methods 0.000 description 84
- 235000019439 ethyl acetate Nutrition 0.000 description 84
- 239000000243 solution Substances 0.000 description 83
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 82
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 79
- 235000019341 magnesium sulphate Nutrition 0.000 description 79
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 79
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 78
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 64
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 62
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 55
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 55
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 52
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 52
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 51
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 47
- 238000002844 melting Methods 0.000 description 43
- 230000008018 melting Effects 0.000 description 43
- 235000017557 sodium bicarbonate Nutrition 0.000 description 41
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 41
- 239000011541 reaction mixture Substances 0.000 description 40
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 37
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- 239000005457 ice water Substances 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 23
- 239000000047 product Substances 0.000 description 21
- 150000003254 radicals Chemical class 0.000 description 21
- 230000002829 reductive effect Effects 0.000 description 21
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 18
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 239000010410 layer Substances 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-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
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 11
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- 230000002349 favourable effect Effects 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- 230000008020 evaporation Effects 0.000 description 8
- SERHXTVXHNVDKA-UHFFFAOYSA-N pantolactone Chemical compound CC1(C)COC(=O)C1O SERHXTVXHNVDKA-UHFFFAOYSA-N 0.000 description 8
- 230000002285 radioactive effect Effects 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- 229920000858 Cyclodextrin Polymers 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- LFJJGHGXHXXDFT-UHFFFAOYSA-N 3-bromooxolan-2-one Chemical compound BrC1CCOC1=O LFJJGHGXHXXDFT-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 208000006673 asthma Diseases 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- 239000011521 glass Substances 0.000 description 6
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 6
- OMIVCRYZSXDGAB-UHFFFAOYSA-N 1,4-butanediyl Chemical group [CH2]CC[CH2] OMIVCRYZSXDGAB-UHFFFAOYSA-N 0.000 description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 5
- 206010012438 Dermatitis atopic Diseases 0.000 description 5
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 5
- 125000000815 N-oxide group Chemical group 0.000 description 5
- 206010039085 Rhinitis allergic Diseases 0.000 description 5
- 201000010105 allergic rhinitis Diseases 0.000 description 5
- 201000008937 atopic dermatitis Diseases 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 238000004811 liquid chromatography Methods 0.000 description 5
- 239000000825 pharmaceutical preparation Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 4
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 208000002205 allergic conjunctivitis Diseases 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 208000024998 atopic conjunctivitis Diseases 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 230000002327 eosinophilic effect Effects 0.000 description 4
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 4
- 230000022023 interleukin-5 production Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000001632 sodium acetate Substances 0.000 description 4
- 235000017281 sodium acetate Nutrition 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
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Classifications
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0491—Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0461—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0463—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0468—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A—HUMAN NECESSITIES
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- 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
- A61P37/08—Antiallergic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Optics & Photonics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Ophthalmology & Optometry (AREA)
- Reproductive Health (AREA)
- Gynecology & Obstetrics (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP99870170 | 1999-08-06 | ||
| EP99126035 | 1999-12-27 | ||
| PCT/EP2000/007358 WO2001010866A1 (en) | 1999-08-06 | 2000-07-31 | Interleukin-5 inhibiting 6-azauracil derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20020096A2 true HRP20020096A2 (en) | 2005-10-31 |
Family
ID=26153219
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20020096A HRP20020096A2 (en) | 1999-08-06 | 2002-01-30 | Interleukin-5 inhibiting 6-azauracil derivatives |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US6911444B2 (sk) |
| EP (1) | EP1206471B1 (sk) |
| JP (1) | JP2003506451A (sk) |
| KR (1) | KR100795484B1 (sk) |
| CN (1) | CN1188410C (sk) |
| AR (1) | AR025046A1 (sk) |
| AT (1) | ATE318811T1 (sk) |
| AU (1) | AU780047B2 (sk) |
| BG (1) | BG106367A (sk) |
| BR (1) | BR0013014A (sk) |
| CA (1) | CA2380759A1 (sk) |
| CO (1) | CO5050264A1 (sk) |
| CZ (1) | CZ2002356A3 (sk) |
| DE (1) | DE60026312T2 (sk) |
| EA (1) | EA004740B1 (sk) |
| EE (1) | EE200200057A (sk) |
| ES (1) | ES2260031T3 (sk) |
| HK (1) | HK1048634B (sk) |
| HR (1) | HRP20020096A2 (sk) |
| HU (1) | HUP0202692A3 (sk) |
| IL (1) | IL147976A0 (sk) |
| MX (1) | MXPA02001343A (sk) |
| MY (1) | MY133512A (sk) |
| NO (1) | NO322386B1 (sk) |
| NZ (1) | NZ516506A (sk) |
| PL (1) | PL353475A1 (sk) |
| SK (1) | SK1642002A3 (sk) |
| TR (1) | TR200200310T2 (sk) |
| TW (1) | TWI271404B (sk) |
| WO (1) | WO2001010866A1 (sk) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7186855B2 (en) | 2001-06-11 | 2007-03-06 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
| US6818787B2 (en) | 2001-06-11 | 2004-11-16 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
| US8048917B2 (en) | 2005-04-06 | 2011-11-01 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
| WO2003072554A1 (en) * | 2002-02-28 | 2003-09-04 | Takeda Chemical Industries, Ltd. | Azole compounds |
| EP1758874A1 (en) * | 2004-05-29 | 2007-03-07 | 7TM Pharma A/S | Substituted thiazoleacetic acids as crth2 ligands |
| EP2331541B1 (en) | 2008-09-04 | 2015-04-22 | Boehringer Ingelheim International GmbH | Indolizine inhibitors of leukotriene production |
| JP4743340B1 (ja) * | 2009-10-28 | 2011-08-10 | セントラル硝子株式会社 | 保護膜形成用薬液 |
| US8420655B2 (en) | 2009-12-04 | 2013-04-16 | Boehringer Ingelheim International Gmbh | Benzimidazole inhibitors of leukotriene production |
| EA201300250A1 (ru) | 2010-08-16 | 2013-08-30 | Бёрингер Ингельхайм Интернациональ Гмбх | Оксадиазольные ингибиторы продуцирования лейкотриена |
| EP2609092B1 (en) | 2010-08-26 | 2015-04-01 | Boehringer Ingelheim International GmbH | Oxadiazole inhibitors of leukotriene production |
| AU2011305667A1 (en) | 2010-09-23 | 2013-03-21 | Boehringer Ingelheim International Gmbh | Oxadiazole inhibitors of leukotriene production |
| JP5828188B2 (ja) * | 2010-09-23 | 2015-12-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ロイコトリエン産生のオキサジアゾール阻害剤 |
| JP5928958B2 (ja) | 2010-10-29 | 2016-06-01 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ロイコトリエン生成のベンゾイミダゾールインヒビター |
| WO2012061169A1 (en) | 2010-11-01 | 2012-05-10 | Boehringer Ingelheim International Gmbh | Benzimidazole inhibitors of leukotriene production |
| WO2012082817A1 (en) | 2010-12-16 | 2012-06-21 | Boehringer Ingelheim International Gmbh | Biarylamide inhibitors of leukotriene production |
| AR089853A1 (es) | 2012-02-01 | 2014-09-24 | Boehringer Ingelheim Int | Inhibidores de oxadiazol de la produccion de leucotrienos para terapia de combinacion, composicion farmaceutica, uso |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US42416A (en) * | 1864-04-19 | Improvement in harvesters | ||
| US10177A (en) * | 1853-11-01 | Improved pen and pencil case | ||
| FR2476087A1 (fr) * | 1980-02-18 | 1981-08-21 | Roussel Uclaf | Nouvelles oximes derivees de l'acide 3-alkyloxy ou 3-alkyl-thiomethyl 7-amino thiazolyl acetamido cephalosporanique, leur procede de preparation et leur application comme medicaments |
| CA1244024A (en) | 1984-08-01 | 1988-11-01 | Gustaaf M. Boeckx | .alpha.- ARYL-4-(4,5-DIHYDRO-3,5-DIOXO-1,2,4-TRIAZIN- 2(3H)-YL)BENZENEACETONITRILES |
| US4631278A (en) | 1984-08-01 | 1986-12-23 | Janssen Pharmaceutica N.V. | Anti-protozoal α-aryl-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)-benzeneacetonitrile derivatives, pharmaceutical compositions, and method of use therefor |
| GB8602342D0 (en) | 1986-01-30 | 1986-03-05 | Janssen Pharmaceutica Nv | 5 6-dihydro-2-(substituted phenyl)-1 2 4-triazine-3 5(2h 4h)-diones |
| TR200000153T2 (tr) * | 1997-07-10 | 2000-07-21 | Janssen Pharmaceutica N.V. | İl-5 inhibite eden 6-azaurasil türevleri. |
| CN1261881A (zh) | 1997-07-10 | 2000-08-02 | 詹森药业有限公司 | 作为il－5－抑制剂的6－氮杂尿嘧啶衍生物 |
| EP0987265A1 (en) | 1998-09-18 | 2000-03-22 | Janssen Pharmaceutica N.V. | Interleukin-5 inhibiting 6-azauracil derivatives |
-
2000
- 2000-07-31 AT AT00948015T patent/ATE318811T1/de not_active IP Right Cessation
- 2000-07-31 CA CA002380759A patent/CA2380759A1/en not_active Abandoned
- 2000-07-31 CN CNB008113394A patent/CN1188410C/zh not_active Expired - Fee Related
- 2000-07-31 BR BR0013014-1A patent/BR0013014A/pt not_active Application Discontinuation
- 2000-07-31 EE EEP200200057A patent/EE200200057A/xx unknown
- 2000-07-31 JP JP2001515675A patent/JP2003506451A/ja not_active Withdrawn
- 2000-07-31 KR KR1020027000704A patent/KR100795484B1/ko not_active IP Right Cessation
- 2000-07-31 CZ CZ2002356A patent/CZ2002356A3/cs unknown
- 2000-07-31 MX MXPA02001343A patent/MXPA02001343A/es active IP Right Grant
- 2000-07-31 SK SK164-2002A patent/SK1642002A3/sk not_active Application Discontinuation
- 2000-07-31 WO PCT/EP2000/007358 patent/WO2001010866A1/en active IP Right Grant
- 2000-07-31 EA EA200200232A patent/EA004740B1/ru not_active IP Right Cessation
- 2000-07-31 ES ES00948015T patent/ES2260031T3/es not_active Expired - Lifetime
- 2000-07-31 AU AU61609/00A patent/AU780047B2/en not_active Ceased
- 2000-07-31 IL IL14797600A patent/IL147976A0/xx not_active IP Right Cessation
- 2000-07-31 EP EP00948015A patent/EP1206471B1/en not_active Expired - Lifetime
- 2000-07-31 HU HU0202692A patent/HUP0202692A3/hu unknown
- 2000-07-31 TR TR2002/00310T patent/TR200200310T2/xx unknown
- 2000-07-31 DE DE60026312T patent/DE60026312T2/de not_active Expired - Fee Related
- 2000-07-31 NZ NZ516506A patent/NZ516506A/xx unknown
- 2000-07-31 PL PL00353475A patent/PL353475A1/xx unknown
- 2000-08-03 MY MYPI20003534 patent/MY133512A/en unknown
- 2000-08-04 CO CO00058843A patent/CO5050264A1/es unknown
- 2000-08-04 TW TW089115824A patent/TWI271404B/zh not_active IP Right Cessation
- 2000-08-04 AR ARP000104044A patent/AR025046A1/es unknown
-
2002
- 2002-01-30 HR HR20020096A patent/HRP20020096A2/hr not_active Application Discontinuation
- 2002-01-30 BG BG06367A patent/BG106367A/bg unknown
- 2002-02-05 NO NO20020565A patent/NO322386B1/no not_active IP Right Cessation
- 2002-02-14 US US10/075,876 patent/US6911444B2/en not_active Expired - Fee Related
-
2003
- 2003-01-28 HK HK03100718.8A patent/HK1048634B/zh not_active IP Right Cessation
Also Published As
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