HRP980107A2 - Pyrazine compounds - Google Patents

Pyrazine compounds

Info

Publication number: HRP980107A2
Authority: HR; Croatia
Prior art keywords: compound; formula; pyrazine; trichlorophenyl; alkyl
Prior art date: 1997-03-01

Application number

HR9708183.0A

Other languages

English (en)

Croatian (hr)

Inventor

Michael Simon Loft

Original Assignee

Glaxo Group Ltd

Priority date (The priority date 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 date listed.)

1997-03-01

Filing date

1998-02-27

Publication date

1998-12-31

1997-03-01 Priority claimed from GBGB9704275.8A external-priority patent/GB9704275D0/en

1997-04-23 Priority claimed from GBGB9708183.0A external-priority patent/GB9708183D0/en

1998-02-27 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

1998-12-31 Publication of HRP980107A2 publication Critical patent/HRP980107A2/hr

Links

150000003216 pyrazines Chemical class 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims description 148
238000000034 method Methods 0.000 claims description 37
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 23
229910052739 hydrogen Inorganic materials 0.000 claims description 20
239000001257 hydrogen Substances 0.000 claims description 20
125000005843 halogen group Chemical group 0.000 claims description 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
208000002193 Pain Diseases 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 11
208000020925 Bipolar disease Diseases 0.000 claims description 10
238000006243 chemical reaction Methods 0.000 claims description 10
125000000623 heterocyclic group Chemical group 0.000 claims description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
206010015037 epilepsy Diseases 0.000 claims description 9
229910052757 nitrogen Inorganic materials 0.000 claims description 9
208000035475 disorder Diseases 0.000 claims description 8
NNXUYJFHOVCRSM-UHFFFAOYSA-N 3-(2,3,5-trichlorophenyl)pyrazine-2,6-diamine Chemical group NC1=NC(N)=CN=C1C1=CC(Cl)=CC(Cl)=C1Cl NNXUYJFHOVCRSM-UHFFFAOYSA-N 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
239000003795 chemical substances by application Substances 0.000 claims description 6
230000004770 neurodegeneration Effects 0.000 claims description 6
125000001624 naphthyl group Chemical group 0.000 claims description 5
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
208000028683 bipolar I disease Diseases 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
208000015122 neurodegenerative disease Diseases 0.000 claims description 3
230000003647 oxidation Effects 0.000 claims description 3
238000007254 oxidation reaction Methods 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
230000002265 prevention Effects 0.000 claims description 3
229940079593 drug Drugs 0.000 claims description 2
230000004112 neuroprotection Effects 0.000 claims 2
230000009467 reduction Effects 0.000 claims 2
206010012335 Dependence Diseases 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
238000007363 ring formation reaction Methods 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 claims 1
239000000203 mixture Substances 0.000 description 60
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
239000000243 solution Substances 0.000 description 31
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
238000009472 formulation Methods 0.000 description 24
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
-1 among others Chemical class 0.000 description 19
239000003826 tablet Substances 0.000 description 18
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 15
239000000725 suspension Substances 0.000 description 15
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
239000000706 filtrate Substances 0.000 description 14
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
206010010904 Convulsion Diseases 0.000 description 11
238000003818 flash chromatography Methods 0.000 description 11
239000000047 product Substances 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
239000004480 active ingredient Substances 0.000 description 10
239000003480 eluent Substances 0.000 description 10
UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 10
238000010992 reflux Methods 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
UTJAINMFLNITNP-UHFFFAOYSA-N n-[6-amino-5-(2,3,5-trichlorophenyl)pyrazin-2-yl]acetamide Chemical compound NC1=NC(NC(=O)C)=CN=C1C1=CC(Cl)=CC(Cl)=C1Cl UTJAINMFLNITNP-UHFFFAOYSA-N 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
239000002775 capsule Substances 0.000 description 7
230000008569 process Effects 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
239000004615 ingredient Substances 0.000 description 6
239000007788 liquid Substances 0.000 description 6
239000003208 petroleum Substances 0.000 description 6
239000002904 solvent Substances 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
OPBCCRZCYTUJMS-UHFFFAOYSA-N (2,3,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=CC(Cl)=C1Cl OPBCCRZCYTUJMS-UHFFFAOYSA-N 0.000 description 5
BOLCKGGORFPPJC-UHFFFAOYSA-N 3-bromo-6-chloropyrazin-2-amine Chemical compound NC1=NC(Cl)=CN=C1Br BOLCKGGORFPPJC-UHFFFAOYSA-N 0.000 description 5
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
239000000969 carrier Substances 0.000 description 5
239000008187 granular material Substances 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
RHPZDWZDFQMHEY-UHFFFAOYSA-N 3,5-diamino-6-(2,3,5-trichlorophenyl)pyrazine-2-carbaldehyde Chemical compound N1=C(C=O)C(N)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1Cl RHPZDWZDFQMHEY-UHFFFAOYSA-N 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
238000005481 NMR spectroscopy Methods 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
239000012458 free base Substances 0.000 description 4
239000007903 gelatin capsule Substances 0.000 description 4
208000002551 irritable bowel syndrome Diseases 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
IEHYTQGRBOBLAM-UHFFFAOYSA-N n-(6-amino-5-bromopyrazin-2-yl)acetamide Chemical compound CC(=O)NC1=CN=C(Br)C(N)=N1 IEHYTQGRBOBLAM-UHFFFAOYSA-N 0.000 description 4
USKQEAQRRNUXAR-UHFFFAOYSA-N n-[6-amino-5-(2,5-dichlorophenyl)pyrazin-2-yl]acetamide Chemical compound NC1=NC(NC(=O)C)=CN=C1C1=CC(Cl)=CC=C1Cl USKQEAQRRNUXAR-UHFFFAOYSA-N 0.000 description 4
238000002360 preparation method Methods 0.000 description 4
YACSOXWFJOAKCM-UHFFFAOYSA-N 2-methyl-n-[6-(2-methylpropanoylamino)-5-(2,3,5-trichlorophenyl)pyrazin-2-yl]propanamide Chemical compound CC(C)C(=O)NC1=NC(NC(=O)C(C)C)=CN=C1C1=CC(Cl)=CC(Cl)=C1Cl YACSOXWFJOAKCM-UHFFFAOYSA-N 0.000 description 3
ZQPYGEVVJSGWLW-UHFFFAOYSA-N 3-methyl-5-(2,3,5-trichlorophenyl)pyrazine-2,6-diamine Chemical compound N1=C(N)C(C)=NC(C=2C(=C(Cl)C=C(Cl)C=2)Cl)=C1N ZQPYGEVVJSGWLW-UHFFFAOYSA-N 0.000 description 3
CRVPQFAORCSDMH-UHFFFAOYSA-N 5-bromo-6-chloropyrazin-2-amine Chemical compound NC1=CN=C(Br)C(Cl)=N1 CRVPQFAORCSDMH-UHFFFAOYSA-N 0.000 description 3
TXIVDCNXCRALRM-UHFFFAOYSA-N 6-chloro-3-(2,3,5-trichlorophenyl)pyrazin-2-amine Chemical compound NC1=NC(Cl)=CN=C1C1=CC(Cl)=CC(Cl)=C1Cl TXIVDCNXCRALRM-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
GTPPBOVRISNFPC-UHFFFAOYSA-N [3,5-diamino-6-(2,3,5-trichlorophenyl)pyrazin-2-yl]methanol Chemical compound N1=C(CO)C(N)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1Cl GTPPBOVRISNFPC-UHFFFAOYSA-N 0.000 description 3
239000002253 acid Substances 0.000 description 3
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
239000012267 brine Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
230000002140 halogenating effect Effects 0.000 description 3
150000002367 halogens Chemical class 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
239000010410 layer Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
210000000214 mouth Anatomy 0.000 description 3
ZZAXOGPGZVNOCU-UHFFFAOYSA-N n-[6-(cyclopropanecarbonylamino)-5-(2,3,5-trichlorophenyl)pyrazin-2-yl]cyclopropanecarboxamide Chemical compound ClC1=CC(Cl)=C(Cl)C(C=2C(=NC(NC(=O)C3CC3)=CN=2)NC(=O)C2CC2)=C1 ZZAXOGPGZVNOCU-UHFFFAOYSA-N 0.000 description 3
JLGTZSMUAOZNBN-UHFFFAOYSA-N n-[6-amino-3-(2,3,5-trichlorophenyl)pyrazin-2-yl]-2-methylpropanamide Chemical compound CC(C)C(=O)NC1=NC(N)=CN=C1C1=CC(Cl)=CC(Cl)=C1Cl JLGTZSMUAOZNBN-UHFFFAOYSA-N 0.000 description 3
YXIHYXUXPIFBLV-UHFFFAOYSA-N n-[6-amino-3-(2,3,5-trichlorophenyl)pyrazin-2-yl]cyclopropanecarboxamide Chemical compound N=1C(N)=CN=C(C=2C(=C(Cl)C=C(Cl)C=2)Cl)C=1NC(=O)C1CC1 YXIHYXUXPIFBLV-UHFFFAOYSA-N 0.000 description 3
IRXIOADGVGKLEG-UHFFFAOYSA-N n-[6-amino-5-(2,3,5-trichlorophenyl)pyrazin-2-yl]-2-methylpropanamide Chemical compound NC1=NC(NC(=O)C(C)C)=CN=C1C1=CC(Cl)=CC(Cl)=C1Cl IRXIOADGVGKLEG-UHFFFAOYSA-N 0.000 description 3
UXFFCHPHWHNEOV-UHFFFAOYSA-N n-[6-amino-5-(2,3,5-trichlorophenyl)pyrazin-2-yl]cyclopropanecarboxamide Chemical compound C=1N=C(C=2C(=C(Cl)C=C(Cl)C=2)Cl)C(N)=NC=1NC(=O)C1CC1 UXFFCHPHWHNEOV-UHFFFAOYSA-N 0.000 description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
239000000843 powder Substances 0.000 description 3
239000008213 purified water Substances 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
239000007787 solid Substances 0.000 description 3
239000011343 solid material Substances 0.000 description 3
239000000829 suppository Substances 0.000 description 3
239000008215 water for injection Substances 0.000 description 3
TYIKXPOMOYDGCS-UHFFFAOYSA-N (2,3-dichlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Cl)=C1Cl TYIKXPOMOYDGCS-UHFFFAOYSA-N 0.000 description 2
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
WOIGJFAVHOCDDW-UHFFFAOYSA-N 1-bromo-2,3,5-trichlorobenzene Chemical compound ClC1=CC(Cl)=C(Cl)C(Br)=C1 WOIGJFAVHOCDDW-UHFFFAOYSA-N 0.000 description 2
DJYRZTCLVDKWBL-UHFFFAOYSA-N 2,3,5-trichlorobenzaldehyde Chemical compound ClC1=CC(Cl)=C(Cl)C(C=O)=C1 DJYRZTCLVDKWBL-UHFFFAOYSA-N 0.000 description 2
ICYIOZICRJJCPZ-UHFFFAOYSA-N 2-[[cyano-(2,3,5-trichlorophenyl)methyl]amino]ethanimidamide;hydrobromide Chemical compound Br.NC(=N)CNC(C#N)C1=CC(Cl)=CC(Cl)=C1Cl ICYIOZICRJJCPZ-UHFFFAOYSA-N 0.000 description 2
JTPXVCKCLBROOJ-UHFFFAOYSA-N 2-amino-6-chloropyrazine Chemical compound NC1=CN=CC(Cl)=N1 JTPXVCKCLBROOJ-UHFFFAOYSA-N 0.000 description 2
DTPADCOGQUOGHT-UHFFFAOYSA-N 2-bromo-4,6-dichloroaniline Chemical compound NC1=C(Cl)C=C(Cl)C=C1Br DTPADCOGQUOGHT-UHFFFAOYSA-N 0.000 description 2
LNJZJDLDXQQJSG-UHFFFAOYSA-N 2-phenylpyrazine Chemical class C1=CC=CC=C1C1=CN=CC=N1 LNJZJDLDXQQJSG-UHFFFAOYSA-N 0.000 description 2
COGWHXCGIHDGSY-UHFFFAOYSA-N 3,5-diamino-6-(2,3,5-trichlorophenyl)pyrazine-2-carbonitrile Chemical compound N1=C(C#N)C(N)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1Cl COGWHXCGIHDGSY-UHFFFAOYSA-N 0.000 description 2
AILXTOKHVYCLGJ-UHFFFAOYSA-N 3-(2,3-dichlorophenyl)-6-n,6-n-dimethylpyrazine-2,6-diamine Chemical compound NC1=NC(N(C)C)=CN=C1C1=CC=CC(Cl)=C1Cl AILXTOKHVYCLGJ-UHFFFAOYSA-N 0.000 description 2
CQGJBSYKOSGFBB-UHFFFAOYSA-N 3-(2,3-dichlorophenyl)pyrazine-2,6-diamine Chemical compound NC1=NC(N)=CN=C1C1=CC=CC(Cl)=C1Cl CQGJBSYKOSGFBB-UHFFFAOYSA-N 0.000 description 2
FOZHLJAOQPMVIN-UHFFFAOYSA-N 3-bromo-5-(2,3,5-trichlorophenyl)pyrazine-2,6-diamine Chemical compound N1=C(Br)C(N)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1Cl FOZHLJAOQPMVIN-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
ICGLPKIVTVWCFT-UHFFFAOYSA-N 4-methylbenzenesulfonohydrazide Chemical compound CC1=CC=C(S(=O)(=O)NN)C=C1 ICGLPKIVTVWCFT-UHFFFAOYSA-N 0.000 description 2
WROMQORHKQJNAM-UHFFFAOYSA-N 6-(4-methylpiperazin-1-yl)-3-(2,3,5-trichlorophenyl)pyrazin-2-amine Chemical compound C1CN(C)CCN1C1=CN=C(C=2C(=C(Cl)C=C(Cl)C=2)Cl)C(N)=N1 WROMQORHKQJNAM-UHFFFAOYSA-N 0.000 description 2
UAZFZHXRKHSGLQ-UHFFFAOYSA-N 6-chloro-3-(2,3-dichlorophenyl)pyrazin-2-amine Chemical compound NC1=NC(Cl)=CN=C1C1=CC=CC(Cl)=C1Cl UAZFZHXRKHSGLQ-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
241000220479 Acacia Species 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
235000010643 Leucaena leucocephala Nutrition 0.000 description 2
206010049816 Muscle tightness Diseases 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
125000000217 alkyl group Chemical group 0.000 description 2
229940035676 analgesics Drugs 0.000 description 2
239000000730 antalgic agent Substances 0.000 description 2
239000002585 base Substances 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
230000037396 body weight Effects 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
ZDQWVKDDJDIVAL-UHFFFAOYSA-N catecholborane Chemical compound C1=CC=C2O[B]OC2=C1 ZDQWVKDDJDIVAL-UHFFFAOYSA-N 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/20—Nitrogen atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- 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
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Addiction (AREA)
Hospice & Palliative Care (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Detergent Compositions (AREA)

HR9708183.0A 1997-03-01 1998-02-27 Pyrazine compounds HRP980107A2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9704275.8A GB9704275D0 (en)	1997-03-01	1997-03-01	Pharmacologically active compound
GBGB9708183.0A GB9708183D0 (en)	1997-04-23	1997-04-23	Pharmacologically active compound

Publications (1)

Publication Number	Publication Date
HRP980107A2 true HRP980107A2 (en)	1998-12-31

Family

ID=26311097

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR9708183.0A HRP980107A2 (en)	1997-03-01	1998-02-27	Pyrazine compounds

Country Status (46)

Country	Link
US (2)	US6255307B1 (es)
EP (1)	EP0966448B1 (es)
JP (1)	JP3369189B2 (es)
KR (1)	KR100544263B1 (es)
CN (1)	CN1105111C (es)
AP (1)	AP9901632A0 (es)
AR (1)	AR011174A1 (es)
AT (1)	ATE251143T1 (es)
AU (1)	AU732915B2 (es)
BG (1)	BG103723A (es)
BR (1)	BR9807814B1 (es)
CA (1)	CA2282585C (es)
CO (1)	CO4950513A1 (es)
CZ (1)	CZ295618B6 (es)
DE (1)	DE69818643T2 (es)
DK (1)	DK0966448T3 (es)
EA (1)	EA002102B1 (es)
EE (1)	EE9900376A (es)
ES (1)	ES2205469T3 (es)
GE (1)	GEP20012555B (es)
GT (1)	GT199800046A (es)
HK (1)	HK1023116A1 (es)
HN (2)	HN1998000036A (es)
HR (1)	HRP980107A2 (es)
HU (1)	HU225852B1 (es)
ID (1)	ID22850A (es)
IL (1)	IL131293A (es)
IS (1)	IS5163A (es)
JO (1)	JO2035B1 (es)
MA (1)	MA26473A1 (es)
MY (1)	MY118612A (es)
NO (1)	NO313383B1 (es)
NZ (1)	NZ337121A (es)
OA (1)	OA11151A (es)
PA (1)	PA8448201A1 (es)
PE (1)	PE58299A1 (es)
PL (1)	PL192864B1 (es)
PT (1)	PT966448E (es)
SI (1)	SI0966448T1 (es)
SK (1)	SK117399A3 (es)
SV (1)	SV1998000029A (es)
TR (1)	TR199902082T2 (es)
TW (1)	TW513416B (es)
UY (1)	UY24911A1 (es)
WO (1)	WO1998038174A1 (es)
YU (1)	YU40799A (es)

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JP2005533014A (ja)	2002-04-26	2005-11-04	ファルマシア・アンド・アップジョン・カンパニー・エルエルシー	置換ピラジン誘導体
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SE0203753D0 (sv) *	2002-12-17	2002-12-17	Astrazeneca Ab	New compounds
SE0203754D0 (sv) *	2002-12-17	2002-12-17	Astrazeneca Ab	New compounds
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GB0800741D0 (en)	2008-01-16	2008-02-20	Univ Greenwich	Cyclic triazo and diazo sodium channel blockers
GB201111712D0 (en)	2011-07-08	2011-08-24	Gosforth Ct Holdings Pty Ltd	Pharmaceutical compositions
FR3001151B1 (fr)	2013-01-21	2016-04-08	Pf Medicament	Association d'un bloqueur de courant sodique lent et d'un inhibiteur du courant if sinusal et les compositions pharmarceutiques la contenant
JO3517B1 (ar) *	2014-01-17	2020-07-05	Novartis Ag	ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2
MX2018015625A (es)	2016-06-14	2019-03-06	Novartis Ag	Compuestos y composiciones para inhibir la actividad de shp2.
UY37341A (es)	2016-07-22	2017-11-30	Flamel Ireland Ltd	Formulaciones de gamma-hidroxibutirato de liberación modificada con farmacocinética mejorada
US11602513B1 (en)	2016-07-22	2023-03-14	Flamel Ireland Limited	Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics
US11602512B1 (en)	2016-07-22	2023-03-14	Flamel Ireland Limited	Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics
US11986451B1 (en)	2016-07-22	2024-05-21	Flamel Ireland Limited	Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics
US11504347B1 (en)	2016-07-22	2022-11-22	Flamel Ireland Limited	Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics
CN108101857B (zh) *	2016-11-24	2021-09-03	韶远科技（上海)有限公司	制取2-氨基-3-溴-6-氯吡嗪的可放大工艺
CN107011273A (zh) *	2017-05-04	2017-08-04	无锡捷化医药科技有限公司	一种合成6‑碘‑3‑(2,3‑二氯苯基)吡嗪‑2‑胺的方法
WO2020178695A1 (en)	2019-03-01	2020-09-10	Flamel Ireland Limited	Gamma-hydroxybutyrate compositions having improved pharmacokinetics in the fed state
US11779557B1 (en)	2022-02-07	2023-10-10	Flamel Ireland Limited	Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics
US11583510B1 (en)	2022-02-07	2023-02-21	Flamel Ireland Limited	Methods of administering gamma hydroxybutyrate formulations after a high-fat meal
CN115611700A (zh) *	2022-10-11	2023-01-17	辽宁东大光明化工科技有限责任公司	一种1-溴-2,5-二氯-3-氟苯的制备方法

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1998
- 1998-02-23 MA MA24973A patent/MA26473A1/fr unknown
- 1998-02-24 PE PE1998000134A patent/PE58299A1/es not_active Application Discontinuation
- 1998-02-26 JO JO19982035A patent/JO2035B1/en active
- 1998-02-26 PT PT98913592T patent/PT966448E/pt unknown
- 1998-02-26 NZ NZ337121A patent/NZ337121A/xx not_active IP Right Cessation
- 1998-02-26 AU AU68237/98A patent/AU732915B2/en not_active Ceased
- 1998-02-26 IL IL13129398A patent/IL131293A/xx not_active IP Right Cessation
- 1998-02-26 YU YU40799A patent/YU40799A/sh unknown
- 1998-02-26 EA EA199900687A patent/EA002102B1/ru not_active IP Right Cessation
- 1998-02-26 CA CA002282585A patent/CA2282585C/en not_active Expired - Fee Related
- 1998-02-26 US US09/380,062 patent/US6255307B1/en not_active Expired - Fee Related
- 1998-02-26 AP AP9901632A patent/AP9901632A0/xx unknown
- 1998-02-26 EP EP98913592A patent/EP0966448B1/en not_active Expired - Lifetime
- 1998-02-26 GE GEAP19984976A patent/GEP20012555B/en unknown
- 1998-02-26 ID IDW990951A patent/ID22850A/id unknown
- 1998-02-26 GT GT199800046A patent/GT199800046A/es unknown
- 1998-02-26 DK DK98913592T patent/DK0966448T3/da active
- 1998-02-26 CO CO98010500A patent/CO4950513A1/es unknown
- 1998-02-26 MY MYPI98000852A patent/MY118612A/en unknown
- 1998-02-26 WO PCT/EP1998/001077 patent/WO1998038174A1/en active IP Right Grant
- 1998-02-26 CZ CZ19993111A patent/CZ295618B6/cs not_active IP Right Cessation
- 1998-02-26 PL PL335441A patent/PL192864B1/pl unknown
- 1998-02-26 HU HU0001802A patent/HU225852B1/hu not_active IP Right Cessation
- 1998-02-26 BR BRPI9807814-3A patent/BR9807814B1/pt not_active IP Right Cessation
- 1998-02-26 TR TR1999/02082T patent/TR199902082T2/xx unknown
- 1998-02-26 KR KR1019997007937A patent/KR100544263B1/ko not_active IP Right Cessation
- 1998-02-26 EE EEP199900376A patent/EE9900376A/xx unknown
- 1998-02-26 SK SK1173-99A patent/SK117399A3/sk unknown
- 1998-02-26 CN CN98804593A patent/CN1105111C/zh not_active Expired - Fee Related
- 1998-02-26 SI SI9830578T patent/SI0966448T1/xx unknown
- 1998-02-26 DE DE69818643T patent/DE69818643T2/de not_active Expired - Lifetime
- 1998-02-26 AT AT98913592T patent/ATE251143T1/de active
- 1998-02-26 JP JP53731098A patent/JP3369189B2/ja not_active Expired - Fee Related
- 1998-02-26 ES ES98913592T patent/ES2205469T3/es not_active Expired - Lifetime
- 1998-02-27 PA PA19988448201A patent/PA8448201A1/es unknown
- 1998-02-27 AR ARP980100906A patent/AR011174A1/es active IP Right Grant
- 1998-02-27 UY UY24911A patent/UY24911A1/es unknown
- 1998-02-27 SV SV1998000029A patent/SV1998000029A/es not_active Application Discontinuation
- 1998-02-27 HN HN1998000036A patent/HN1998000036A/es unknown
- 1998-02-27 HR HR9708183.0A patent/HRP980107A2/hr not_active Application Discontinuation
- 1998-03-03 TW TW087103079A patent/TW513416B/zh not_active IP Right Cessation
1999
- 1999-02-11 HN HN1999000019A patent/HN1999000019A/es unknown
- 1999-08-24 IS IS5163A patent/IS5163A/is unknown
- 1999-08-27 OA OA9900196A patent/OA11151A/en unknown
- 1999-08-31 NO NO19994213A patent/NO313383B1/no not_active IP Right Cessation
- 1999-09-09 BG BG103723A patent/BG103723A/bg unknown
2000
- 2000-04-10 HK HK00102173A patent/HK1023116A1/xx not_active IP Right Cessation
2001
- 2001-05-16 US US09/855,703 patent/US6599905B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CN1253551A (zh)	2000-05-17
IL131293A (en)	2003-07-31
MY118612A (en)	2004-12-31
OA11151A (en)	2003-04-22
ES2205469T3 (es)	2004-05-01
TR199902082T2 (xx)	2000-04-21
NO994213L (no)	1999-10-29
TW513416B (en)	2002-12-11
UY24911A1 (es)	2000-12-29
GEP20012555B (en)	2001-10-25
PE58299A1 (es)	1999-06-23
DK0966448T3 (da)	2004-02-02
YU40799A (sh)	2001-09-28
EA199900687A1 (ru)	2000-04-24
EA002102B1 (ru)	2001-12-24
PL192864B1 (pl)	2006-12-29
AU732915B2 (en)	2001-05-03
AP9901632A0 (en)	1999-09-30
HK1023116A1 (en)	2000-09-01
NO994213D0 (no)	1999-08-31
US6255307B1 (en)	2001-07-03
ID22850A (id)	1999-12-09
EP0966448A1 (en)	1999-12-29
JP3369189B2 (ja)	2003-01-20
CZ295618B6 (cs)	2005-09-14
AR011174A1 (es)	2000-08-02
PL335441A1 (en)	2000-04-25
AU6823798A (en)	1998-09-18
HU225852B1 (en)	2007-11-28
NO313383B1 (no)	2002-09-23
MA26473A1 (fr)	2004-12-20
BR9807814A (pt)	2000-02-22
IS5163A (is)	1999-08-24
HUP0001802A3 (en)	2001-07-30
US20020169172A1 (en)	2002-11-14
DE69818643D1 (de)	2003-11-06
CA2282585C (en)	2006-06-06
PA8448201A1 (es)	2000-05-24
SV1998000029A (es)	1998-12-11
IL131293A0 (en)	2001-01-28
SK117399A3 (en)	2000-06-12
BR9807814B1 (pt)	2009-01-13
EP0966448B1 (en)	2003-10-01
HUP0001802A2 (hu)	2001-05-28
ATE251143T1 (de)	2003-10-15
CO4950513A1 (es)	2000-09-01
CA2282585A1 (en)	1998-09-03
EE9900376A (et)	2000-04-17
JO2035B1 (en)	1999-05-15
SI0966448T1 (en)	2004-04-30
DE69818643T2 (de)	2004-10-07
PT966448E (pt)	2004-02-27
BG103723A (bg)	2001-05-31
NZ337121A (en)	2001-03-30
WO1998038174A1 (en)	1998-09-03
JP2000511203A (ja)	2000-08-29
KR20000075859A (ko)	2000-12-26
HN1998000036A (es)	1999-08-23
GT199800046A (es)	1999-08-20
US6599905B2 (en)	2003-07-29
CZ311199A3 (cs)	2000-02-16
KR100544263B1 (ko)	2006-01-23
CN1105111C (zh)	2003-04-09
HN1999000019A (es)	1999-08-23

Legal Events

Date	Code	Title	Description
1998-12-31	A1OB	Publication of a patent application
1999-06-16	AIPI	Request for the grant of a patent on the basis of a substantive examination of a patent application
2001-02-27	ODRP	Renewal fee for the maintenance of a patent	Payment date: 20010227 Year of fee payment: 4
2004-04-21	ODBC	Application rejected

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