NO327055B1 - Hepatit C virus-polymerase-inhibitorer, samt anvendelse og fremgangsmate for fremstilling derav og farmasoytisk preparat - Google Patents
Hepatit C virus-polymerase-inhibitorer, samt anvendelse og fremgangsmate for fremstilling derav og farmasoytisk preparat Download PDFInfo
- Publication number
- NO327055B1 NO327055B1 NO20040282A NO20040282A NO327055B1 NO 327055 B1 NO327055 B1 NO 327055B1 NO 20040282 A NO20040282 A NO 20040282A NO 20040282 A NO20040282 A NO 20040282A NO 327055 B1 NO327055 B1 NO 327055B1
- Authority
- NO
- Norway
- Prior art keywords
- alkyl
- cycloalkyl
- aryl
- het
- 6alkyl
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 41
- 239000003112 inhibitor Substances 0.000 title claims description 13
- 238000002360 preparation method Methods 0.000 title claims description 10
- 241000711549 Hepacivirus C Species 0.000 title description 40
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 125000003118 aryl group Chemical group 0.000 claims description 273
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 267
- 125000000217 alkyl group Chemical group 0.000 claims description 210
- 125000000623 heterocyclic group Chemical group 0.000 claims description 118
- 150000001875 compounds Chemical class 0.000 claims description 95
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 65
- 229910052757 nitrogen Inorganic materials 0.000 claims description 61
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 52
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 49
- -1 COOR<161> Chemical group 0.000 claims description 47
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- 239000002904 solvent Substances 0.000 claims description 35
- 150000002367 halogens Chemical class 0.000 claims description 31
- 125000001188 haloalkyl group Chemical group 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 239000003054 catalyst Substances 0.000 claims description 19
- 229910052751 metal Inorganic materials 0.000 claims description 18
- 239000002184 metal Substances 0.000 claims description 18
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 17
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- 108060004795 Methyltransferase Proteins 0.000 claims description 14
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- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
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- 230000015572 biosynthetic process Effects 0.000 claims description 9
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 229910052763 palladium Inorganic materials 0.000 claims description 8
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 7
- 239000000654 additive Substances 0.000 claims description 7
- 230000000996 additive effect Effects 0.000 claims description 7
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- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 239000003446 ligand Substances 0.000 claims description 7
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- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 6
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 229910052700 potassium Inorganic materials 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
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- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 4
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 3
- 229960003805 amantadine Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 229940047124 interferons Drugs 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 1
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- 239000000203 mixture Substances 0.000 description 85
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- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
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- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
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- 150000002739 metals Chemical class 0.000 description 1
- QOQJFUQDXVNLMK-UHFFFAOYSA-N methyl 2-bromo-3-cyclohexyl-1h-indole-6-carboxylate Chemical compound BrC=1NC2=CC(C(=O)OC)=CC=C2C=1C1CCCCC1 QOQJFUQDXVNLMK-UHFFFAOYSA-N 0.000 description 1
- APUHQLOCOQOILB-UHFFFAOYSA-N methyl 3-(cyclohexen-1-yl)-2-phenyl-1h-indole-6-carboxylate Chemical compound N1C2=CC(C(=O)OC)=CC=C2C(C=2CCCCC=2)=C1C1=CC=CC=C1 APUHQLOCOQOILB-UHFFFAOYSA-N 0.000 description 1
- WJEBNIVVLJEIKE-UHFFFAOYSA-N methyl 3-amino-4-iodobenzoate Chemical compound COC(=O)C1=CC=C(I)C(N)=C1 WJEBNIVVLJEIKE-UHFFFAOYSA-N 0.000 description 1
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- 125000001624 naphthyl group Chemical group 0.000 description 1
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- 239000008363 phosphate buffer Substances 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
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- GHUURDQYRGVEHX-UHFFFAOYSA-N prop-1-ynylbenzene Chemical compound CC#CC1=CC=CC=C1 GHUURDQYRGVEHX-UHFFFAOYSA-N 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
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- 239000012312 sodium hydride Substances 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- XZPVPNZTYPUODG-UHFFFAOYSA-M sodium;chloride;dihydrate Chemical compound O.O.[Na+].[Cl-] XZPVPNZTYPUODG-UHFFFAOYSA-M 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
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- 239000007929 subcutaneous injection Substances 0.000 description 1
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- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
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- 238000007910 systemic administration Methods 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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- 238000005382 thermal cycling Methods 0.000 description 1
- FCEHBMOGCRZNNI-UHFFFAOYSA-N thianaphthalene Natural products C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 1
- HZPQJLDBYJZHLL-UHFFFAOYSA-N thiophen-2-ylstannane Chemical compound [SnH3]C1=CC=CS1 HZPQJLDBYJZHLL-UHFFFAOYSA-N 0.000 description 1
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- 229940015849 thiophene Drugs 0.000 description 1
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- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
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- 230000007704 transition Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- ZGWZWRHJHVTXEL-UHFFFAOYSA-N trimethyl(thiophen-2-yl)stannane Chemical compound C[Sn](C)(C)C1=CC=CS1 ZGWZWRHJHVTXEL-UHFFFAOYSA-N 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- DOICFEXUJKISKP-UHFFFAOYSA-L triphenylstannyl n-[2-(triphenylstannylsulfanylcarbothioylamino)ethyl]carbamodithioate Chemical class C=1C=CC=CC=1[Sn](C=1C=CC=CC=1)(C=1C=CC=CC=1)SC(=S)NCCNC(=S)S[Sn](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 DOICFEXUJKISKP-UHFFFAOYSA-L 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 108010087967 type I signal peptidase Proteins 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
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- 238000005406 washing Methods 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes 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 carbon atoms of the hetero ring
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A61P37/00—Drugs for immunological or allergic disorders
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- 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
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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US30767401P | 2001-07-25 | 2001-07-25 | |
US33806101P | 2001-12-07 | 2001-12-07 | |
PCT/CA2002/001127 WO2003010140A2 (en) | 2001-07-25 | 2002-07-18 | Hepatitis c virus polymerase inhibitors with heterobicyclic structure |
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NO327055B1 true NO327055B1 (no) | 2009-04-14 |
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NO20040282A NO327055B1 (no) | 2001-07-25 | 2004-01-21 | Hepatit C virus-polymerase-inhibitorer, samt anvendelse og fremgangsmate for fremstilling derav og farmasoytisk preparat |
NO20040322A NO333121B1 (no) | 2001-07-25 | 2004-01-23 | Virus-polymerase-inhibitorer, farmasoytisk preparat omfattende slike samt anvendelse av slike for fremstilling av medikamenter for behandling av sykdom |
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NO20040322A NO333121B1 (no) | 2001-07-25 | 2004-01-23 | Virus-polymerase-inhibitorer, farmasoytisk preparat omfattende slike samt anvendelse av slike for fremstilling av medikamenter for behandling av sykdom |
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EP (5) | EP2335700A1 (de) |
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AU (2) | AU2002355150B2 (de) |
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PL (2) | PL372125A1 (de) |
PT (2) | PT1414797E (de) |
RS (3) | RS20090517A (de) |
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