CA2326522A1 - Pyrrolo[1,2-a]pyrazine spla2 inhibitor - Google Patents
Pyrrolo[1,2-a]pyrazine spla2 inhibitor Download PDFInfo
- Publication number
- CA2326522A1 CA2326522A1 CA002326522A CA2326522A CA2326522A1 CA 2326522 A1 CA2326522 A1 CA 2326522A1 CA 002326522 A CA002326522 A CA 002326522A CA 2326522 A CA2326522 A CA 2326522A CA 2326522 A1 CA2326522 A1 CA 2326522A1
- Authority
- CA
- Canada
- Prior art keywords
- pyrazin
- iii
- ethyl
- compound
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000003112 inhibitor Substances 0.000 title claims description 18
- QSLLFYVBWXWUQT-UHFFFAOYSA-N 7-Azaindolizine Chemical compound C1=NC=CN2C=CC=C21 QSLLFYVBWXWUQT-UHFFFAOYSA-N 0.000 title claims description 15
- 239000000203 mixture Substances 0.000 claims abstract description 193
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 52
- 125000001424 substituent group Chemical group 0.000 claims abstract description 44
- 239000000651 prodrug Substances 0.000 claims abstract description 43
- 229940002612 prodrug Drugs 0.000 claims abstract description 43
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 229910052717 sulfur Chemical group 0.000 claims abstract description 38
- 239000012453 solvate Substances 0.000 claims abstract description 29
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 24
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 21
- 230000002452 interceptive effect Effects 0.000 claims abstract description 19
- 125000005647 linker group Chemical group 0.000 claims abstract description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 15
- 125000004429 atom Chemical group 0.000 claims abstract description 13
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 13
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 13
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 13
- 230000002378 acidificating effect Effects 0.000 claims abstract description 10
- 102000005473 Secretory Phospholipases A2 Human genes 0.000 claims abstract description 8
- 108010031873 Secretory Phospholipases A2 Proteins 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 282
- -1 amino, amidino Chemical group 0.000 claims description 129
- 239000002253 acid Substances 0.000 claims description 68
- 238000000034 method Methods 0.000 claims description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims description 45
- 229910052736 halogen Inorganic materials 0.000 claims description 31
- 239000004480 active ingredient Substances 0.000 claims description 29
- 150000002367 halogens Chemical class 0.000 claims description 28
- 125000003545 alkoxy group Chemical group 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 125000001188 haloalkyl group Chemical group 0.000 claims description 19
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- 239000011734 sodium Substances 0.000 claims description 17
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000004414 alkyl thio group Chemical group 0.000 claims description 14
- 229910052708 sodium Inorganic materials 0.000 claims description 13
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 11
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 10
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 9
- 125000004104 aryloxy group Chemical group 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 208000027866 inflammatory disease Diseases 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 125000005110 aryl thio group Chemical group 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- 239000000194 fatty acid Substances 0.000 claims description 7
- 229930195729 fatty acid Natural products 0.000 claims description 7
- 150000004665 fatty acids Chemical class 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 125000003944 tolyl group Chemical group 0.000 claims description 4
- 125000005023 xylyl group Chemical group 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 3
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 150000003555 thioacetals Chemical class 0.000 claims description 3
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 3
- AIOLKLJBYGLZPE-UHFFFAOYSA-N 2-(6-benzyl-7-ethyl-8-oxamoylpyrrolo[1,2-a]pyrazin-1-yl)oxyacetic acid Chemical compound N12C=CN=C(OCC(O)=O)C2=C(C(=O)C(N)=O)C(CC)=C1CC1=CC=CC=C1 AIOLKLJBYGLZPE-UHFFFAOYSA-N 0.000 claims description 2
- BEAWEDTYZZVVOK-UHFFFAOYSA-N 2-[7-ethyl-6-[(3-fluorophenyl)methyl]-3-methyl-8-oxamoylpyrrolo[1,2-a]pyrazin-1-yl]oxyacetic acid Chemical compound N12C=C(C)N=C(OCC(O)=O)C2=C(C(=O)C(N)=O)C(CC)=C1CC1=CC=CC(F)=C1 BEAWEDTYZZVVOK-UHFFFAOYSA-N 0.000 claims description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 2
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 2
- 230000001575 pathological effect Effects 0.000 claims description 2
- PQTMJTYTUIMVJW-UHFFFAOYSA-M sodium;2-[7-ethyl-3-methyl-8-oxamoyl-6-[(2-thiophen-2-ylphenyl)methyl]pyrrolo[1,2-a]pyrazin-1-yl]oxyacetate Chemical compound [Na+].N12C=C(C)N=C(OCC([O-])=O)C2=C(C(=O)C(N)=O)C(CC)=C1CC1=CC=CC=C1C1=CC=CS1 PQTMJTYTUIMVJW-UHFFFAOYSA-M 0.000 claims description 2
- CJEZSTYETSQXCX-UHFFFAOYSA-M sodium;2-[7-ethyl-6-[[2-(4-fluorophenyl)phenyl]methyl]-3-methyl-8-oxamoylpyrrolo[1,2-a]pyrazin-1-yl]oxyacetate Chemical compound [Na+].N12C=C(C)N=C(OCC([O-])=O)C2=C(C(=O)C(N)=O)C(CC)=C1CC1=CC=CC=C1C1=CC=C(F)C=C1 CJEZSTYETSQXCX-UHFFFAOYSA-M 0.000 claims description 2
- 229910006069 SO3H Inorganic materials 0.000 claims 2
- UKVXXOGIYNUKNI-UHFFFAOYSA-N 2-morpholin-4-ylethyl 2-[7-ethyl-3-methyl-8-oxamoyl-6-[(2-thiophen-2-ylphenyl)methyl]pyrrolo[1,2-a]pyrazin-1-yl]oxyacetate Chemical compound N12C=C(C)N=C(OCC(=O)OCCN3CCOCC3)C2=C(C(=O)C(N)=O)C(CC)=C1CC1=CC=CC=C1C1=CC=CS1 UKVXXOGIYNUKNI-UHFFFAOYSA-N 0.000 claims 1
- RWDKCYLRENEADL-UHFFFAOYSA-N 2-morpholin-4-ylethyl 2-[7-ethyl-6-[[2-(4-fluorophenyl)phenyl]methyl]-3-methyl-8-oxamoylpyrrolo[1,2-a]pyrazin-1-yl]oxyacetate Chemical compound N12C=C(C)N=C(OCC(=O)OCCN3CCOCC3)C2=C(C(=O)C(N)=O)C(CC)=C1CC1=CC=CC=C1C1=CC=C(F)C=C1 RWDKCYLRENEADL-UHFFFAOYSA-N 0.000 claims 1
- FPYZBOHVNSHJOW-UHFFFAOYSA-N ethyl 2-[7-ethyl-3-methyl-8-oxamoyl-6-[(2-thiophen-2-ylphenyl)methyl]pyrrolo[1,2-a]pyrazin-1-yl]oxyacetate Chemical compound CCC=1C(C(=O)C(N)=O)=C2C(OCC(=O)OCC)=NC(C)=CN2C=1CC1=CC=CC=C1C1=CC=CS1 FPYZBOHVNSHJOW-UHFFFAOYSA-N 0.000 claims 1
- KWOKUBFKCQLUTO-UHFFFAOYSA-N ethyl 2-[7-ethyl-6-[[2-(4-fluorophenyl)phenyl]methyl]-3-methyl-8-oxamoylpyrrolo[1,2-a]pyrazin-1-yl]oxyacetate Chemical compound CCC=1C(C(=O)C(N)=O)=C2C(OCC(=O)OCC)=NC(C)=CN2C=1CC1=CC=CC=C1C1=CC=C(F)C=C1 KWOKUBFKCQLUTO-UHFFFAOYSA-N 0.000 claims 1
- CKRALENLOPTHBS-UHFFFAOYSA-N methyl 2-[7-ethyl-3-methyl-8-oxamoyl-6-[(2-thiophen-2-ylphenyl)methyl]pyrrolo[1,2-a]pyrazin-1-yl]oxyacetate Chemical compound N12C=C(C)N=C(OCC(=O)OC)C2=C(C(=O)C(N)=O)C(CC)=C1CC1=CC=CC=C1C1=CC=CS1 CKRALENLOPTHBS-UHFFFAOYSA-N 0.000 claims 1
- WZNNHRVEUIAUGP-UHFFFAOYSA-N methyl 2-[7-ethyl-6-[[2-(4-fluorophenyl)phenyl]methyl]-3-methyl-8-oxamoylpyrrolo[1,2-a]pyrazin-1-yl]oxyacetate Chemical compound N12C=C(C)N=C(OCC(=O)OC)C2=C(C(=O)C(N)=O)C(CC)=C1CC1=CC=CC=C1C1=CC=C(F)C=C1 WZNNHRVEUIAUGP-UHFFFAOYSA-N 0.000 claims 1
- 239000004615 ingredient Substances 0.000 abstract description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 141
- 239000000243 solution Substances 0.000 description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- 239000002904 solvent Substances 0.000 description 52
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 50
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 48
- 239000012044 organic layer Substances 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
- 239000003795 chemical substances by application Substances 0.000 description 46
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 43
- 238000005160 1H NMR spectroscopy Methods 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 42
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- 239000013078 crystal Substances 0.000 description 36
- 229910052731 fluorine Inorganic materials 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
- 239000011541 reaction mixture Substances 0.000 description 34
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 31
- 239000000460 chlorine Substances 0.000 description 31
- 238000001816 cooling Methods 0.000 description 29
- 238000002844 melting Methods 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 239000012267 brine Substances 0.000 description 28
- 230000008018 melting Effects 0.000 description 28
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
- 238000009472 formulation Methods 0.000 description 24
- 229910052720 vanadium Inorganic materials 0.000 description 23
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
- 229910052938 sodium sulfate Inorganic materials 0.000 description 22
- 235000011152 sodium sulphate Nutrition 0.000 description 22
- 238000010626 work up procedure Methods 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 230000002829 reductive effect Effects 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 238000010898 silica gel chromatography Methods 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
- 235000019341 magnesium sulphate Nutrition 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- 239000007858 starting material Substances 0.000 description 16
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 239000010410 layer Substances 0.000 description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
- 239000003921 oil Substances 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 13
- 229910052770 Uranium Inorganic materials 0.000 description 13
- 101150041968 CDC13 gene Proteins 0.000 description 11
- 238000004821 distillation Methods 0.000 description 11
- 239000005457 ice water Substances 0.000 description 11
- 125000001624 naphthyl group Chemical group 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 206010040047 Sepsis Diseases 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 239000012230 colorless oil Substances 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 229920002472 Starch Polymers 0.000 description 9
- 238000000921 elemental analysis Methods 0.000 description 9
- 239000008107 starch Substances 0.000 description 9
- 235000019698 starch Nutrition 0.000 description 9
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
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- 239000003814 drug Substances 0.000 description 7
- 235000019359 magnesium stearate Nutrition 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical class NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 229910052796 boron Inorganic materials 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 5
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 5
- 102000015439 Phospholipases Human genes 0.000 description 5
- 108010064785 Phospholipases Proteins 0.000 description 5
- 206010040070 Septic Shock Diseases 0.000 description 5
- 208000006673 asthma Diseases 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 230000000747 cardiac effect Effects 0.000 description 5
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 5
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- NYCVSSWORUBFET-UHFFFAOYSA-M sodium;bromite Chemical compound [Na+].[O-]Br=O NYCVSSWORUBFET-UHFFFAOYSA-M 0.000 description 1
- CRWJEUDFKNYSBX-UHFFFAOYSA-N sodium;hypobromite Chemical compound [Na+].Br[O-] CRWJEUDFKNYSBX-UHFFFAOYSA-N 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 208000008203 tachypnea Diseases 0.000 description 1
- 206010043089 tachypnoea Diseases 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000005323 thioketone group Chemical group 0.000 description 1
- ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
- 125000002827 triflate group Chemical class FC(S(=O)(=O)O*)(F)F 0.000 description 1
- XQKBFQXWZCFNFF-UHFFFAOYSA-K triiodosamarium Chemical compound I[Sm](I)I XQKBFQXWZCFNFF-UHFFFAOYSA-K 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical class CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 1
- 230000003156 vasculitic effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical class [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- 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
-
- 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
-
- 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
- A61P17/00—Drugs for dermatological disorders
-
- 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
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- 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
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial 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
- A61P37/08—Antiallergic agents
-
- 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
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- C07D495/12—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 three hetero rings
- C07D495/14—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8599798 | 1998-03-31 | ||
| JP10/85997 | 1998-03-31 | ||
| JP24473598 | 1998-08-31 | ||
| JP10/244735 | 1998-08-31 | ||
| PCT/JP1999/001670 WO1999051605A1 (en) | 1998-03-31 | 1999-03-31 | PYRROLO[1,2-a]PYRAZINE sPLA2 INHIBITOR |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2326522A1 true CA2326522A1 (en) | 1999-10-14 |
Family
ID=26427020
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002326522A Abandoned CA2326522A1 (en) | 1998-03-31 | 1999-03-31 | Pyrrolo[1,2-a]pyrazine spla2 inhibitor |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US6407104B1 (https=) |
| EP (1) | EP1066290A1 (https=) |
| JP (1) | JP4412521B2 (https=) |
| KR (1) | KR20010042307A (https=) |
| CN (1) | CN1303384A (https=) |
| AU (1) | AU3054399A (https=) |
| BR (1) | BR9909345A (https=) |
| CA (1) | CA2326522A1 (https=) |
| HU (1) | HUP0102981A3 (https=) |
| NO (1) | NO20004881L (https=) |
| WO (1) | WO1999051605A1 (https=) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU6004799A (en) | 1998-10-14 | 2000-05-01 | Shionogi & Co., Ltd. | Remedies or preventives for ischemic reflow failure |
| AU6015600A (en) | 1999-07-19 | 2001-02-05 | Shionogi & Co., Ltd. | Tricyclic compounds having spla2-inhibitory activities |
| WO2001014378A1 (en) | 1999-08-23 | 2001-03-01 | Shionogi & Co., Ltd. | PYRROLOTRIAZINE DERIVATIVES HAVING sPLA2-INHIBITORY ACTIVITIES |
| AU7559600A (en) * | 1999-10-15 | 2001-04-23 | Shionogi & Co., Ltd. | V type and/or x type spla2 inhibitors |
| US6756376B1 (en) | 1999-11-15 | 2004-06-29 | Shionogi & Co., Ltd. | Tricyclic azaindolizine derivatives having an sPLA2-inhibitory activities |
| US6967200B2 (en) | 2000-06-29 | 2005-11-22 | Shionogi & Co., Ltd. | Remedies for cirrhosis |
| WO2002000621A1 (en) * | 2000-06-29 | 2002-01-03 | Shionogi & Co., Ltd. | Compounds exhibiting x-type spla2 inhibiting effect |
| AUPQ876400A0 (en) * | 2000-07-14 | 2000-08-03 | University Of Queensland, The | Compositions and method of using them |
| WO2002012249A2 (en) * | 2000-08-04 | 2002-02-14 | Eli Lilly And Company | Substituted pyrrole compounds and their use as spla2 inhibitors |
| TWI314457B (https=) * | 2001-03-19 | 2009-09-11 | Shionogi & Co | |
| US6730694B1 (en) | 2001-07-20 | 2004-05-04 | Eli Lilly And Company | sPLA2 inhibitors |
| DE10155727A1 (de) * | 2001-11-13 | 2003-05-28 | Morphochem Ag | Serin Protease Inhibitoren |
| AUPS282602A0 (en) | 2002-06-07 | 2002-06-27 | Garvan Institute Of Medical Research | Method of inhibiting cell proliferation |
| EP1910385B1 (en) * | 2005-08-04 | 2013-07-24 | Sirtris Pharmaceuticals, Inc. | Benzothiazoles and thiazolopyridines as sirtuin modulators |
| TW200916472A (en) * | 2007-06-20 | 2009-04-16 | Sirtris Pharmaceuticals Inc | Sirtuin modulating compounds |
| NZ624963A (en) | 2009-04-29 | 2016-07-29 | Amarin Pharmaceuticals Ie Ltd | Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same |
| CN105622616A (zh) * | 2016-02-25 | 2016-06-01 | 上海雅本化学有限公司 | 一种4-氯吡咯并嘧啶的制备方法 |
| EP4378924A4 (en) * | 2021-09-17 | 2025-09-03 | Mitsui Chemicals Inc | PROCESS FOR PRODUCING A (METH)ACRYLAMIDE COMPOUND |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL109309A (en) * | 1993-04-16 | 2000-06-29 | Lilly Co Eli | 1-H-indole-3-acetic acid hydrazide SPLA2 inhibitors and pharmaceutical compositions containing them |
| IL109311A0 (en) | 1993-04-16 | 1994-07-31 | Lilly Co Eli | 1H-indole-3-acetamide sPla2 inhibitors |
| BR9501404A (pt) | 1994-04-01 | 1996-03-05 | Lilly Co Eli | 1H-indol-3 glioxilamida e formulação farmacèutica |
| US5641800A (en) | 1994-07-21 | 1997-06-24 | Eli Lilly And Company | 1H-indole-1-functional sPLA2 inhibitors |
| BR9508298A (pt) * | 1994-07-21 | 1998-11-03 | Shionogi & Co | Inibidores de indolizina de spla2 |
| US6214876B1 (en) * | 1994-07-21 | 2001-04-10 | Eli Lilly And Company | Indene-1-acetamide sPLA2 inhibitors |
| ES2174034T3 (es) | 1995-12-13 | 2002-11-01 | Lilly Co Eli | Naftilglioxamidas como inhibidores de spla2 |
| EP0779271B1 (en) | 1995-12-13 | 2001-08-01 | Eli Lilly And Company | Naphthyl acetamides as sPLA2 inhibitors |
| CA2269203A1 (en) | 1996-10-30 | 1998-05-07 | Nicholas James Bach | Substituted tricyclics |
| US5916922A (en) | 1996-12-03 | 1999-06-29 | Eli Lilly And Company | Phenyl glyoxamides as SPLA2 inhibitors |
| US6353128B1 (en) | 1996-12-03 | 2002-03-05 | Eli Lilly And Company | Phenyl acetamides as sPLA2 inhibitors |
| ID18983A (id) | 1996-12-04 | 1998-05-28 | Lilly Co Eli | Pirazola sebagai inhibitor sekresi fosfolipase a2 non-pankreas pada manusia |
| US5919774A (en) | 1996-12-10 | 1999-07-06 | Eli Lilly And Company | Pyrroles as sPLA2 inhibitors |
| TW455581B (en) | 1997-06-26 | 2001-09-21 | Lilly Co Eli | Process for preparing 4-substituted-1H-indole-3-glyoxamides |
-
1999
- 1999-03-31 HU HU0102981A patent/HUP0102981A3/hu unknown
- 1999-03-31 WO PCT/JP1999/001670 patent/WO1999051605A1/en not_active Ceased
- 1999-03-31 KR KR1020007010855A patent/KR20010042307A/ko not_active Ceased
- 1999-03-31 CA CA002326522A patent/CA2326522A1/en not_active Abandoned
- 1999-03-31 JP JP2000542326A patent/JP4412521B2/ja not_active Expired - Fee Related
- 1999-03-31 AU AU30543/99A patent/AU3054399A/en not_active Abandoned
- 1999-03-31 CN CN99806627A patent/CN1303384A/zh active Pending
- 1999-03-31 US US09/623,591 patent/US6407104B1/en not_active Expired - Fee Related
- 1999-03-31 EP EP99912066A patent/EP1066290A1/en not_active Ceased
- 1999-03-31 BR BR9909345-6A patent/BR9909345A/pt not_active IP Right Cessation
-
2000
- 2000-09-28 NO NO20004881A patent/NO20004881L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2002530268A (ja) | 2002-09-17 |
| AU3054399A (en) | 1999-10-25 |
| NO20004881L (no) | 2000-11-28 |
| US6407104B1 (en) | 2002-06-18 |
| BR9909345A (pt) | 2000-12-12 |
| JP4412521B2 (ja) | 2010-02-10 |
| NO20004881D0 (no) | 2000-09-28 |
| WO1999051605A1 (en) | 1999-10-14 |
| EP1066290A1 (en) | 2001-01-10 |
| HUP0102981A3 (en) | 2002-10-28 |
| CN1303384A (zh) | 2001-07-11 |
| KR20010042307A (ko) | 2001-05-25 |
| HUP0102981A2 (hu) | 2002-01-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued | ||
| FZDE | Discontinued |
Effective date: 20040331 |