DE60010126T2 - Verzweigte substituierte aminoderivate vom 3-amino-1-phenyl-1h(1,2,4)triazol, verfahren zu deren herstellung und sie enthaltende pharmazeutische zusammensetzungen - Google Patents
Verzweigte substituierte aminoderivate vom 3-amino-1-phenyl-1h(1,2,4)triazol, verfahren zu deren herstellung und sie enthaltende pharmazeutische zusammensetzungen Download PDFInfo
- Publication number
- DE60010126T2 DE60010126T2 DE60010126T DE60010126T DE60010126T2 DE 60010126 T2 DE60010126 T2 DE 60010126T2 DE 60010126 T DE60010126 T DE 60010126T DE 60010126 T DE60010126 T DE 60010126T DE 60010126 T2 DE60010126 T2 DE 60010126T2
- Authority
- DE
- Germany
- Prior art keywords
- cyclopropyl
- propyl
- group
- methylphenyl
- ethyl
- 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.)
- Expired - Lifetime
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- 238000000034 method Methods 0.000 title claims description 32
- 238000002360 preparation method Methods 0.000 title claims description 26
- 230000008569 process Effects 0.000 title claims description 7
- 150000001412 amines Chemical class 0.000 title description 11
- 239000008194 pharmaceutical composition Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 98
- -1 methylenedioxy Chemical group 0.000 claims description 55
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 46
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 24
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 20
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 20
- 229910052717 sulfur Inorganic materials 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 12
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 12
- 230000015572 biosynthetic process Effects 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
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 239000012453 solvate Substances 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 150000004677 hydrates Chemical class 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 230000001419 dependent effect Effects 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- AJCMNLUWKLXWQG-UHFFFAOYSA-N 1-(2-chloro-4-methoxy-5-methylphenyl)-5-cyclopropyl-n-(2-cyclopropyl-1-phenylethyl)-n-prop-2-ynyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C1=C(C)C(OC)=CC(Cl)=C1N1C(C2CC2)=NC(N(CC#C)C(CC2CC2)C=2C=CC=CC=2)=N1 AJCMNLUWKLXWQG-UHFFFAOYSA-N 0.000 claims description 3
- MVWDDZGGGHOGQO-FTBISJDPSA-N 1-(2-chloro-4-methoxy-5-methylphenyl)-5-cyclopropyl-n-[(1r)-1-(4-fluorophenyl)-2-methoxyethyl]-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C1([C@H](COC)N(CCC)C2=NN(C(C3CC3)=N2)C=2C(=CC(OC)=C(C)C=2)Cl)=CC=C(F)C=C1 MVWDDZGGGHOGQO-FTBISJDPSA-N 0.000 claims description 3
- JMBPFABNJHVOCR-JIDHJSLPSA-N 1-(2-chloro-4-methoxy-5-methylphenyl)-5-cyclopropyl-n-[(1s)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C([C@H](N(CCC)C1=NN(C(C2CC2)=N1)C=1C(=CC(OC)=C(C)C=1)Cl)C=1C=C(F)C(C)=CC=1)C1CC1 JMBPFABNJHVOCR-JIDHJSLPSA-N 0.000 claims description 3
- YKOUFOAKCBVIHB-BOXHHOBZSA-N 1-(2-chloro-4-methoxy-5-methylphenyl)-5-methyl-n-[(1s)-1-phenylbutyl]-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.CCCN([C@@H](CCC)C=1C=CC=CC=1)C(=N1)N=C(C)N1C1=CC(C)=C(OC)C=C1Cl YKOUFOAKCBVIHB-BOXHHOBZSA-N 0.000 claims description 3
- MPPGXEYBOMGQIC-BQAIUKQQSA-N 1-(2-chloro-4-methoxy-5-methylphenyl)-n-[(1s)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C([C@H](N(CCC)C1=NN(C(C)=N1)C=1C(=CC(OC)=C(C)C=1)Cl)C=1C=C(F)C(C)=CC=1)C1CC1 MPPGXEYBOMGQIC-BQAIUKQQSA-N 0.000 claims description 3
- SLIZMVXWEHEBIK-BQAIUKQQSA-N 1-(2-chloro-4-methoxyphenyl)-n-[(1s)-2-cyclopropyl-1-(4-fluorophenyl)ethyl]-5-methyl-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C([C@H](N(CCC)C1=NN(C(C)=N1)C=1C(=CC(OC)=CC=1)Cl)C=1C=CC(F)=CC=1)C1CC1 SLIZMVXWEHEBIK-BQAIUKQQSA-N 0.000 claims description 3
- XUQASNHMDWEVHJ-UHFFFAOYSA-N 1-(2-chloro-4-methylsulfanylphenyl)-n-[2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.N1=C(C)N(C=2C(=CC(SC)=CC=2)Cl)N=C1N(CCC)C(C=1C=C(F)C(C)=CC=1)CC1CC1 XUQASNHMDWEVHJ-UHFFFAOYSA-N 0.000 claims description 3
- HWQKGVPWMDGCTJ-BOXHHOBZSA-N 5-cyclopropyl-1-(2,4-dichlorophenyl)-n-[(1r)-1-(4-fluorophenyl)-2-methoxyethyl]-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C1([C@H](COC)N(CCC)C2=NN(C(C3CC3)=N2)C=2C(=CC(Cl)=CC=2)Cl)=CC=C(F)C=C1 HWQKGVPWMDGCTJ-BOXHHOBZSA-N 0.000 claims description 3
- KQELBZSXYJCFJI-UHFFFAOYSA-N 5-cyclopropyl-n-(2-cyclopropyl-1-phenylethyl)-1-(2,4-dichlorophenyl)-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.N1=C(C2CC2)N(C=2C(=CC(Cl)=CC=2)Cl)N=C1N(CCC)C(C=1C=CC=CC=1)CC1CC1 KQELBZSXYJCFJI-UHFFFAOYSA-N 0.000 claims description 3
- AATNXRAPUFLVHI-SNYZSRNZSA-N 5-cyclopropyl-n-[(1s)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-1-(2,4-dimethylphenyl)-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C([C@H](N(CCC)C1=NN(C(C2CC2)=N1)C=1C(=CC(C)=CC=1)C)C=1C=C(F)C(C)=CC=1)C1CC1 AATNXRAPUFLVHI-SNYZSRNZSA-N 0.000 claims description 3
- UMKBWCOXZVINFP-UHFFFAOYSA-N 5-cyclopropyl-n-[2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-1-(2,4-dichlorophenyl)-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.N1=C(C2CC2)N(C=2C(=CC(Cl)=CC=2)Cl)N=C1N(CCC)C(C=1C=C(F)C(C)=CC=1)CC1CC1 UMKBWCOXZVINFP-UHFFFAOYSA-N 0.000 claims description 3
- UYYYAXJPBMJQFA-FTBISJDPSA-N n-[(1s)-2-cyclopropyl-1-(4-fluorophenyl)ethyl]-1-(2,4-dichlorophenyl)-5-methyl-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C([C@H](N(CCC)C1=NN(C(C)=N1)C=1C(=CC(Cl)=CC=1)Cl)C=1C=CC(F)=CC=1)C1CC1 UYYYAXJPBMJQFA-FTBISJDPSA-N 0.000 claims description 3
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 2
- NEURYOYRKPFLKH-UHFFFAOYSA-N 2-chloro-1-isocyanato-4-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC=C(N=C=O)C(Cl)=C1 NEURYOYRKPFLKH-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 238000005804 alkylation reaction Methods 0.000 claims description 2
- 239000012876 carrier material Substances 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- CZRJUWGPYDDDHQ-UHFFFAOYSA-N 1-(2-chloro-4-methoxy-5-methylphenyl)-5-cyclopropyl-n-(2-cyclopropyl-1-phenylethyl)-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.N1=C(C2CC2)N(C=2C(=CC(OC)=C(C)C=2)Cl)N=C1N(CCC)C(C=1C=CC=CC=1)CC1CC1 CZRJUWGPYDDDHQ-UHFFFAOYSA-N 0.000 claims 1
- WLUPROPNNPYVQN-BQAIUKQQSA-N 1-(2-chloro-4-methoxy-5-methylphenyl)-5-cyclopropyl-n-[(1s)-1-(4-methylphenyl)butyl]-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.CCCN([C@@H](CCC)C=1C=CC(C)=CC=1)C(=NN1C=2C(=CC(OC)=C(C)C=2)Cl)N=C1C1CC1 WLUPROPNNPYVQN-BQAIUKQQSA-N 0.000 claims 1
- NYJLAYDIWPXAPY-FTBISJDPSA-N 1-(2-chloro-4-methoxy-5-methylphenyl)-5-cyclopropyl-n-[(1s)-1-phenylbutyl]-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.CCCN([C@@H](CCC)C=1C=CC=CC=1)C(=NN1C=2C(=CC(OC)=C(C)C=2)Cl)N=C1C1CC1 NYJLAYDIWPXAPY-FTBISJDPSA-N 0.000 claims 1
- VTOYLWIFVFRYHF-UHFFFAOYSA-N 1-(2-chloro-4-methoxy-5-methylphenyl)-5-cyclopropyl-n-[2-cyclopropyl-1-(4-fluorophenyl)ethyl]-n-prop-2-ynyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C1=C(C)C(OC)=CC(Cl)=C1N1C(C2CC2)=NC(N(CC#C)C(CC2CC2)C=2C=CC(F)=CC=2)=N1 VTOYLWIFVFRYHF-UHFFFAOYSA-N 0.000 claims 1
- FVXJMWZVSNUDJY-UHFFFAOYSA-N 1-(2-chloro-4-methoxy-5-methylphenyl)-5-cyclopropyl-n-[2-cyclopropyl-1-(4-fluorophenyl)ethyl]-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.N1=C(C2CC2)N(C=2C(=CC(OC)=C(C)C=2)Cl)N=C1N(CCC)C(C=1C=CC(F)=CC=1)CC1CC1 FVXJMWZVSNUDJY-UHFFFAOYSA-N 0.000 claims 1
- DTBFUKFUWJFYGL-BQAIUKQQSA-N 1-(2-chloro-4-methoxy-5-methylphenyl)-n-[(1s)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-n-prop-2-ynyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C1=C(C)C(OC)=CC(Cl)=C1N1C(C)=NC(N(CC#C)[C@@H](CC2CC2)C=2C=C(F)C(C)=CC=2)=N1 DTBFUKFUWJFYGL-BQAIUKQQSA-N 0.000 claims 1
- BQCIXLNVDJYSHI-FTBISJDPSA-N 1-(2-chloro-4-methoxy-5-methylphenyl)-n-[(1s)-2-cyclopropyl-1-(4-fluorophenyl)ethyl]-5-ethyl-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C([C@H](N(CCC)C1=NN(C(CC)=N1)C=1C(=CC(OC)=C(C)C=1)Cl)C=1C=CC(F)=CC=1)C1CC1 BQCIXLNVDJYSHI-FTBISJDPSA-N 0.000 claims 1
- LVBALXOUXZLSNB-FTBISJDPSA-N 1-(2-chloro-4-methoxy-5-methylphenyl)-n-[(1s)-2-cyclopropyl-1-(4-fluorophenyl)ethyl]-5-methyl-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C([C@H](N(CCC)C1=NN(C(C)=N1)C=1C(=CC(OC)=C(C)C=1)Cl)C=1C=CC(F)=CC=1)C1CC1 LVBALXOUXZLSNB-FTBISJDPSA-N 0.000 claims 1
- JYUMCZIEVLGBIC-BQAIUKQQSA-N 1-(2-chloro-4-methoxy-5-methylphenyl)-n-[(1s)-2-cyclopropyl-1-(4-methylphenyl)ethyl]-5-methyl-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C([C@H](N(CCC)C1=NN(C(C)=N1)C=1C(=CC(OC)=C(C)C=1)Cl)C=1C=CC(C)=CC=1)C1CC1 JYUMCZIEVLGBIC-BQAIUKQQSA-N 0.000 claims 1
- NLTHNJUIHGELQW-UHFFFAOYSA-N 1-(2-chloro-4-methoxy-5-methylphenyl)-n-[2-cyclopropyl-1-(4-fluorophenyl)ethyl]-5-methyl-n-prop-2-ynyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C1=C(C)C(OC)=CC(Cl)=C1N1C(C)=NC(N(CC#C)C(CC2CC2)C=2C=CC(F)=CC=2)=N1 NLTHNJUIHGELQW-UHFFFAOYSA-N 0.000 claims 1
- YHFYDMODNSVAPO-JIDHJSLPSA-N 1-(2-chloro-4-methoxyphenyl)-n-[(1s)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C([C@H](N(CCC)C1=NN(C(C)=N1)C=1C(=CC(OC)=CC=1)Cl)C=1C=C(F)C(C)=CC=1)C1CC1 YHFYDMODNSVAPO-JIDHJSLPSA-N 0.000 claims 1
- PZSMXSNSKGLUSK-FTBISJDPSA-N 5-cyclopropyl-1-(2,4-dichlorophenyl)-n-[(1s)-1-(4-methylphenyl)butyl]-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.CCCN([C@@H](CCC)C=1C=CC(C)=CC=1)C(=NN1C=2C(=CC(Cl)=CC=2)Cl)N=C1C1CC1 PZSMXSNSKGLUSK-FTBISJDPSA-N 0.000 claims 1
- VJGNHJIBHPFWMZ-BOXHHOBZSA-N 5-cyclopropyl-1-(2,4-dichlorophenyl)-n-[(1s)-1-phenylbutyl]-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.CCCN([C@@H](CCC)C=1C=CC=CC=1)C(=NN1C=2C(=CC(Cl)=CC=2)Cl)N=C1C1CC1 VJGNHJIBHPFWMZ-BOXHHOBZSA-N 0.000 claims 1
- UFFYEDWIGUERRK-UHFFFAOYSA-N 5-cyclopropyl-n-[2-cyclopropyl-1-(4-fluorophenyl)ethyl]-1-(2,4-dichlorophenyl)-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.N1=C(C2CC2)N(C=2C(=CC(Cl)=CC=2)Cl)N=C1N(CCC)C(C=1C=CC(F)=CC=1)CC1CC1 UFFYEDWIGUERRK-UHFFFAOYSA-N 0.000 claims 1
- FMGRTADHNQGYEK-BOXHHOBZSA-N n-[(1s)-1-(1,3-benzodioxol-5-yl)-2-cyclopropylethyl]-1-(2,4-dichlorophenyl)-5-methyl-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C([C@H](N(CCC)C1=NN(C(C)=N1)C=1C(=CC(Cl)=CC=1)Cl)C=1C=C2OCOC2=CC=1)C1CC1 FMGRTADHNQGYEK-BOXHHOBZSA-N 0.000 claims 1
- PJNGKNDDDJBUFI-BQAIUKQQSA-N n-[(1s)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-1-(2,4-dichlorophenyl)-5-methyl-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C([C@H](N(CCC)C1=NN(C(C)=N1)C=1C(=CC(Cl)=CC=1)Cl)C=1C=C(F)C(C)=CC=1)C1CC1 PJNGKNDDDJBUFI-BQAIUKQQSA-N 0.000 claims 1
- JZCCEJPJPWXSJU-FTBISJDPSA-N n-[(1s)-2-cyclopropyl-1-(4-fluorophenyl)ethyl]-1-(2,4-dichlorophenyl)-5-ethyl-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C([C@H](N(CCC)C1=NN(C(CC)=N1)C=1C(=CC(Cl)=CC=1)Cl)C=1C=CC(F)=CC=1)C1CC1 JZCCEJPJPWXSJU-FTBISJDPSA-N 0.000 claims 1
- KELFJQSKBQNPMV-BQAIUKQQSA-N n-[(1s)-2-cyclopropyl-1-(4-methylphenyl)ethyl]-1-(2,4-dichlorophenyl)-5-methyl-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.C([C@H](N(CCC)C1=NN(C(C)=N1)C=1C(=CC(Cl)=CC=1)Cl)C=1C=CC(C)=CC=1)C1CC1 KELFJQSKBQNPMV-BQAIUKQQSA-N 0.000 claims 1
- FXJFOIYJZQPVHA-UHFFFAOYSA-N n-[2-cyclopropyl-1-(4-fluorophenyl)ethyl]-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-methyl-n-propyl-1,2,4-triazol-3-amine;hydrochloride Chemical compound Cl.N1=C(C)N(C=2C(=CC(=CC=2Cl)C(F)(F)F)Cl)N=C1N(CCC)C(C=1C=CC(F)=CC=1)CC1CC1 FXJFOIYJZQPVHA-UHFFFAOYSA-N 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- 239000000243 solution Substances 0.000 description 60
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 37
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- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 35
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- 239000000203 mixture Substances 0.000 description 31
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
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- 239000011541 reaction mixture Substances 0.000 description 20
- 229920006395 saturated elastomer Polymers 0.000 description 19
- 229910052938 sodium sulfate Inorganic materials 0.000 description 19
- 235000011152 sodium sulphate Nutrition 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 150000003141 primary amines Chemical class 0.000 description 17
- 239000011780 sodium chloride Substances 0.000 description 17
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- 238000004440 column chromatography Methods 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
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- FPLHNGGABOAXNW-UHFFFAOYSA-N n-[1-(4-methylphenyl)butylidene]hydroxylamine Chemical compound CCCC(=NO)C1=CC=C(C)C=C1 FPLHNGGABOAXNW-UHFFFAOYSA-N 0.000 description 1
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- KZSJNJIPIHZBPD-UHFFFAOYSA-N n-[2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethylidene]hydroxylamine Chemical compound C1=C(F)C(C)=CC=C1C(=NO)CC1CC1 KZSJNJIPIHZBPD-UHFFFAOYSA-N 0.000 description 1
- JDYHZMWBFBEHDN-UHFFFAOYSA-N n-[2-cyclopropyl-1-(4-fluorophenyl)ethylidene]hydroxylamine Chemical compound C=1C=C(F)C=CC=1C(=NO)CC1CC1 JDYHZMWBFBEHDN-UHFFFAOYSA-N 0.000 description 1
- LDNFHCLOBIYCOC-UHFFFAOYSA-N n-[2-cyclopropyl-1-(4-methylphenyl)ethylidene]hydroxylamine Chemical compound C1=CC(C)=CC=C1C(=NO)CC1CC1 LDNFHCLOBIYCOC-UHFFFAOYSA-N 0.000 description 1
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- 230000000955 neuroendocrine Effects 0.000 description 1
- 230000002474 noradrenergic effect Effects 0.000 description 1
- 231100000926 not very toxic Toxicity 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
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- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 150000004031 phenylhydrazines Chemical class 0.000 description 1
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- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000031337 regulation of inflammatory response Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 229940042055 systemic antimycotics triazole derivative Drugs 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 239000000777 urocortin Substances 0.000 description 1
- 239000000780 urotensin Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- MMSLSKDMIZOHRX-WYDAWZGFSA-N α-helical crf(9-41) Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(N)=O MMSLSKDMIZOHRX-WYDAWZGFSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/14—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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- 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
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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
- A61P25/08—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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Gynecology & Obstetrics (AREA)
- Hospice & Palliative Care (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Pregnancy & Childbirth (AREA)
- Nutrition Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9915935A FR2802530B1 (fr) | 1999-12-17 | 1999-12-17 | Nouveaux derives amino substitues ramifies du 3-amino-1-phenyl-1h[1,2,4]triazole, procedes pour leur preparation et compositions pharmaceutiques les contenant |
| FR9915935 | 1999-12-17 | ||
| PCT/FR2000/003536 WO2001044207A2 (fr) | 1999-12-17 | 2000-12-14 | Nouveaux derives amino substitues ramifies du 3-amino-1-phenyl-1h[1,2 4]triazole, procedes pour leur preparation et compositions pharmaceutiques les contenant |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60010126D1 DE60010126D1 (de) | 2004-05-27 |
| DE60010126T2 true DE60010126T2 (de) | 2005-04-28 |
Family
ID=9553380
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60010126T Expired - Lifetime DE60010126T2 (de) | 1999-12-17 | 2000-12-14 | Verzweigte substituierte aminoderivate vom 3-amino-1-phenyl-1h(1,2,4)triazol, verfahren zu deren herstellung und sie enthaltende pharmazeutische zusammensetzungen |
Country Status (33)
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE455546T1 (de) * | 2003-08-06 | 2010-02-15 | Vertex Pharma | Aminotriazol-verbindungen als proteinkinase- hemmer |
| JO3019B1 (ar) | 2006-04-19 | 2016-09-05 | Janssen Pharmaceutica Nv | ثلاثي مستبدل 4،2،1-ثلاثي زولات |
| JP2011500625A (ja) | 2007-10-18 | 2011-01-06 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | トリ置換された１，２，４−トリアゾール |
| JO2784B1 (en) | 2007-10-18 | 2014-03-15 | شركة جانسين فارماسوتيكا ان. في | 5,3,1 - Triazole substitute derivative |
| AR070936A1 (es) * | 2008-03-19 | 2010-05-12 | Janssen Pharmaceutica Nv | 1,2,4 -triazoles trisustituidos |
| JP5486591B2 (ja) | 2008-05-09 | 2014-05-07 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | アセチルコリン受容体モジュレーターとしての三置換ピラゾール |
| US20130225583A1 (en) * | 2010-10-21 | 2013-08-29 | Gerald W. Shipps, Jr. | Substituted amino-triazolyl pde10 inhibitors |
| KR20210064407A (ko) | 2014-01-21 | 2021-06-02 | 뉴로크린 바이오사이언시즈 인코퍼레이티드 | 선천성 부신 과형성 치료를 위한 ｃｒｆ1 수용체 길항제 |
| CN104059027B (zh) * | 2014-07-01 | 2015-10-28 | 河北大学 | 一类含1,2,4-三唑的(e)-甲氧基亚氨基苯乙酸甲酯类化合物及其制备方法和用途 |
| PL3984523T3 (pl) | 2018-12-07 | 2026-02-02 | Neurocrine Biosciences, Inc. | Antagonista receptora crf1, jego formulacje farmaceutyczne i postacie stałe do leczenia wrodzonego przerostu nadnerczy |
| JP7697933B2 (ja) * | 2019-09-25 | 2025-06-24 | オンコアレンディ セラピューティクス エス．エー． | ５－（４－（（２ｓ，５ｓ）－５－（４－クロロベンジル）－２－メチルモルホリノ）ピペリジン－１－イル）－１ｈ－１，２，４－トリアゾール－３－アミンの製造プロセス |
| US12383536B2 (en) | 2019-09-27 | 2025-08-12 | Neurocrine Biosciences, Inc. | CRF receptor antagonists and methods of use |
| ES3039926T3 (en) | 2019-12-04 | 2025-10-27 | Neurocrine Biosciences Inc | Crf receptor antagonists and methods of use |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0285893B1 (en) * | 1987-03-27 | 1992-03-18 | Kumiai Chemical Industry Co., Ltd. | Phenyltriazole derivative and insecticide |
| US5795905A (en) * | 1995-06-06 | 1998-08-18 | Neurocrine Biosciences, Inc. | CRF receptor antagonists and methods relating thereto |
| FR2763337B1 (fr) * | 1997-05-13 | 1999-08-20 | Sanofi Sa | Nouveaux derives du triazole, un procede pour leur preparation et compositions pharmaceutiques les contenant |
-
1999
- 1999-12-17 FR FR9915935A patent/FR2802530B1/fr not_active Expired - Fee Related
-
2000
- 2000-12-14 MX MXPA02006033A patent/MXPA02006033A/es active IP Right Grant
- 2000-12-14 JP JP2001544697A patent/JP4146641B2/ja not_active Expired - Lifetime
- 2000-12-14 DK DK00988916T patent/DK1242389T3/da active
- 2000-12-14 CZ CZ20022099A patent/CZ302460B6/cs not_active IP Right Cessation
- 2000-12-14 TR TR2002/01600T patent/TR200201600T2/xx unknown
- 2000-12-14 AU AU25259/01A patent/AU780711B2/en not_active Ceased
- 2000-12-14 DE DE60010126T patent/DE60010126T2/de not_active Expired - Lifetime
- 2000-12-14 WO PCT/FR2000/003536 patent/WO2001044207A2/fr not_active Ceased
- 2000-12-14 IL IL15003700A patent/IL150037A0/xx active IP Right Grant
- 2000-12-14 EP EP00988916A patent/EP1242389B1/fr not_active Expired - Lifetime
- 2000-12-14 ES ES00988916T patent/ES2219436T3/es not_active Expired - Lifetime
- 2000-12-14 RS YUP-439/02A patent/RS50289B/sr unknown
- 2000-12-14 TR TR2004/01775T patent/TR200401775T4/xx unknown
- 2000-12-14 HU HU0204080A patent/HUP0204080A3/hu unknown
- 2000-12-14 EA EA200200523A patent/EA004957B1/ru not_active IP Right Cessation
- 2000-12-14 KR KR1020027007736A patent/KR100705525B1/ko not_active Expired - Fee Related
- 2000-12-14 UA UA2002064623A patent/UA73333C2/uk unknown
- 2000-12-14 CN CNB00819078XA patent/CN1293061C/zh not_active Expired - Fee Related
- 2000-12-14 CA CA2398772A patent/CA2398772C/fr not_active Expired - Fee Related
- 2000-12-14 ME MEP-121/08A patent/MEP12108A/xx unknown
- 2000-12-14 SK SK850-2002A patent/SK285994B6/sk not_active IP Right Cessation
- 2000-12-14 CO CO00095200A patent/CO5251379A1/es not_active Application Discontinuation
- 2000-12-14 AT AT00988916T patent/ATE264847T1/de active
- 2000-12-14 PL PL355811A patent/PL203819B1/pl not_active IP Right Cessation
- 2000-12-14 EE EEP200200331A patent/EE04778B1/xx not_active IP Right Cessation
- 2000-12-14 US US10/149,499 patent/US6806282B2/en not_active Expired - Lifetime
- 2000-12-14 BR BR0017023-2A patent/BR0017023A/pt active Search and Examination
- 2000-12-14 PT PT00988916T patent/PT1242389E/pt unknown
- 2000-12-15 AR ARP000106666A patent/AR031837A1/es not_active Application Discontinuation
-
2001
- 2001-01-29 TW TW089126997A patent/TWI289554B/zh not_active IP Right Cessation
-
2002
- 2002-05-04 IL IL150037A patent/IL150037A/en not_active IP Right Cessation
- 2002-05-28 IS IS6402A patent/IS2315B/is unknown
- 2002-06-03 ZA ZA200204422A patent/ZA200204422B/en unknown
- 2002-06-13 NO NO20022828A patent/NO20022828L/no not_active Application Discontinuation
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