ES2299588T3 - Inhibidores de la polimerasa del virus de la hepatitis c con estructura heterobiciclica. - Google Patents
Inhibidores de la polimerasa del virus de la hepatitis c con estructura heterobiciclica. Download PDFInfo
- Publication number
- ES2299588T3 ES2299588T3 ES02750715T ES02750715T ES2299588T3 ES 2299588 T3 ES2299588 T3 ES 2299588T3 ES 02750715 T ES02750715 T ES 02750715T ES 02750715 T ES02750715 T ES 02750715T ES 2299588 T3 ES2299588 T3 ES 2299588T3
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- Prior art keywords
- alkyl
- cycloalkyl
- aryl
- het
- optionally substituted
- 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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- 239000003112 inhibitor Substances 0.000 title claims description 21
- 241000700605 Viruses Species 0.000 title description 5
- 208000006454 hepatitis Diseases 0.000 title 1
- 231100000283 hepatitis Toxicity 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 729
- 125000003118 aryl group Chemical group 0.000 claims abstract description 338
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 225
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 143
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 137
- 150000001875 compounds Chemical class 0.000 claims abstract description 104
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 76
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 35
- 150000002367 halogens Chemical class 0.000 claims abstract description 30
- 125000001424 substituent group Chemical group 0.000 claims abstract description 27
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 25
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 14
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 13
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 11
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 9
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims abstract description 9
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims abstract description 7
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 5
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims abstract description 3
- -1 hydroxy, carboxy, amino Chemical group 0.000 claims description 46
- 238000000034 method Methods 0.000 claims description 36
- 239000002904 solvent Substances 0.000 claims description 30
- 238000011282 treatment Methods 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- 229910052751 metal Inorganic materials 0.000 claims description 19
- 239000002184 metal Substances 0.000 claims description 19
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 18
- 239000003054 catalyst Substances 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 14
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical class P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 108060004795 Methyltransferase Proteins 0.000 claims description 10
- 239000003446 ligand Substances 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 238000005859 coupling reaction Methods 0.000 claims description 8
- 229910052763 palladium Inorganic materials 0.000 claims description 8
- 239000000654 additive Substances 0.000 claims description 7
- 230000000996 additive effect Effects 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 230000008878 coupling Effects 0.000 claims description 7
- 238000010168 coupling process Methods 0.000 claims description 7
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 7
- 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 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 230000010076 replication Effects 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 150000004820 halides Chemical group 0.000 claims description 5
- 229910001507 metal halide Inorganic materials 0.000 claims description 5
- 150000005309 metal halides Chemical class 0.000 claims description 5
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 4
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 4
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 239000002955 immunomodulating agent Substances 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 229960000329 ribavirin Drugs 0.000 claims description 4
- 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
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 claims description 3
- 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
- 150000003863 ammonium salts Chemical class 0.000 claims description 3
- 229910052802 copper Inorganic materials 0.000 claims description 3
- 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 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 229940047124 interferons Drugs 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229910052759 nickel Inorganic materials 0.000 claims description 3
- 229910052707 ruthenium Inorganic materials 0.000 claims description 3
- 150000003536 tetrazoles Chemical class 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 108010006035 Metalloproteases Proteins 0.000 claims description 2
- 102000005741 Metalloproteases Human genes 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 229940121354 immunomodulator Drugs 0.000 claims description 2
- 230000002584 immunomodulator Effects 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 16
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 92
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 85
- 239000000203 mixture Substances 0.000 description 83
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
- 238000006243 chemical reaction Methods 0.000 description 48
- 239000000243 solution Substances 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- 241000711549 Hepacivirus C Species 0.000 description 41
- 239000002253 acid Substances 0.000 description 38
- 235000019439 ethyl acetate Nutrition 0.000 description 38
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 32
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 31
- 230000002829 reductive effect Effects 0.000 description 30
- 239000012267 brine Substances 0.000 description 29
- 238000001914 filtration Methods 0.000 description 29
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
- 239000007787 solid Substances 0.000 description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 26
- 235000019341 magnesium sulphate Nutrition 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 25
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- 230000000694 effects Effects 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 19
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- 150000002148 esters Chemical class 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 150000002475 indoles Chemical class 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 16
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 15
- 101800001554 RNA-directed RNA polymerase Proteins 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 238000003756 stirring Methods 0.000 description 14
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 13
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- 238000006880 cross-coupling reaction Methods 0.000 description 13
- ZPRQXVPYQGBZON-UHFFFAOYSA-N 2-bromo-1h-indole Chemical class C1=CC=C2NC(Br)=CC2=C1 ZPRQXVPYQGBZON-UHFFFAOYSA-N 0.000 description 12
- 229910052786 argon Inorganic materials 0.000 description 12
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 11
- 150000003254 radicals Chemical class 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
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- 239000000463 material Substances 0.000 description 9
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- 150000004702 methyl esters Chemical class 0.000 description 9
- QJPQVXSHYBGQGM-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 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 9
- 238000003753 real-time PCR Methods 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 8
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- 239000000872 buffer Substances 0.000 description 8
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- 230000001419 dependent effect Effects 0.000 description 8
- 229940088598 enzyme Drugs 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
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- 238000003786 synthesis reaction Methods 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- GHTDODSYDCPOCW-UHFFFAOYSA-N 1h-indole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C=CNC2=C1 GHTDODSYDCPOCW-UHFFFAOYSA-N 0.000 description 7
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 7
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 7
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- 239000000725 suspension Substances 0.000 description 7
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 6
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
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- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 6
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- 229910000104 sodium hydride Inorganic materials 0.000 description 6
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- 230000005587 bubbling Effects 0.000 description 4
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 4
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- XZPVPNZTYPUODG-UHFFFAOYSA-M sodium;chloride;dihydrate Chemical compound O.O.[Na+].[Cl-] XZPVPNZTYPUODG-UHFFFAOYSA-M 0.000 description 1
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- 125000000547 substituted alkyl group Chemical group 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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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 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
- 229940124597 therapeutic agent Drugs 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
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- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- JUDXOKKZTISQDJ-UHFFFAOYSA-N triphenylphosphane;hydrochloride Chemical compound Cl.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 JUDXOKKZTISQDJ-UHFFFAOYSA-N 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- DJJCXFVJDGTHFX-XVFCMESISA-N uridine 5'-monophosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 DJJCXFVJDGTHFX-XVFCMESISA-N 0.000 description 1
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- 239000011592 zinc chloride Substances 0.000 description 1
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- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
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
- A61P31/12—Antivirals
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- A61P31/12—Antivirals
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- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- 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
-
- 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
-
- 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
-
- 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
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Saccharide Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30767401P | 2001-07-25 | 2001-07-25 | |
| US307674P | 2001-07-25 | ||
| US33806101P | 2001-12-07 | 2001-12-07 | |
| US338061P | 2001-12-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2299588T3 true ES2299588T3 (es) | 2008-06-01 |
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ID=26975871
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02750715T Expired - Lifetime ES2299588T3 (es) | 2001-07-25 | 2002-07-18 | Inhibidores de la polimerasa del virus de la hepatitis c con estructura heterobiciclica. |
| ES02752904T Expired - Lifetime ES2299591T3 (es) | 2001-07-25 | 2002-07-18 | Inhibidores de polimerasa del virus de la hepatitis c con una estructura heterobiciclica. |
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| ES02752904T Expired - Lifetime ES2299591T3 (es) | 2001-07-25 | 2002-07-18 | Inhibidores de polimerasa del virus de la hepatitis c con una estructura heterobiciclica. |
Country Status (33)
Families Citing this family (209)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1470119A4 (en) * | 2001-06-13 | 2005-10-19 | Genesoft Pharmaceuticals Inc | BENZOTHIOPHENE COMPOUNDS WITH ANTI-INFECTIOUS ACTIVITY |
| EP2335700A1 (en) | 2001-07-25 | 2011-06-22 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis C virus polymerase inhibitors with a heterobicylic structure |
| US7294457B2 (en) * | 2001-08-07 | 2007-11-13 | Boehringer Ingelheim (Canada) Ltd. | Direct binding assay for identifying inhibitors of HCV polymerase |
| GB0215293D0 (en) | 2002-07-03 | 2002-08-14 | Rega Foundation | Viral inhibitors |
| US20050075279A1 (en) | 2002-10-25 | 2005-04-07 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis C virus |
| US7098231B2 (en) | 2003-01-22 | 2006-08-29 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| US7223785B2 (en) * | 2003-01-22 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| GB0307891D0 (en) * | 2003-04-04 | 2003-05-14 | Angeletti P Ist Richerche Bio | Chemical compounds,compositions and uses |
| DE602004019518D1 (de) | 2003-04-16 | 2009-04-02 | Bristol Myers Squibb Co | Makrocyclische isochinolinpeptidinhibitoren des hepatitis-c-virus |
| JP2006528685A (ja) * | 2003-05-06 | 2006-12-21 | スミスクライン ビーチャム コーポレーション | 新規化合物 |
| CN1829709A (zh) | 2003-08-01 | 2006-09-06 | 健亚生物科技公司 | 对抗黄病毒的双环咪唑衍生物 |
| WO2005014543A1 (ja) * | 2003-08-06 | 2005-02-17 | Japan Tobacco Inc. | 縮合環化合物及びそのhcvポリメラーゼ阻害剤としての利用 |
| GB0321003D0 (en) | 2003-09-09 | 2003-10-08 | Angeletti P Ist Richerche Bio | Compounds, compositions and uses |
| US7112601B2 (en) | 2003-09-11 | 2006-09-26 | Bristol-Myers Squibb Company | Cycloalkyl heterocycles for treating hepatitis C virus |
| AU2004274051A1 (en) | 2003-09-22 | 2005-03-31 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis C virus |
| EP1677784A4 (en) * | 2003-10-07 | 2010-03-31 | Univ Michigan | ANTIVIRAL INDOL COMPOSITIONS AND METHOD |
| GB0323845D0 (en) * | 2003-10-10 | 2003-11-12 | Angeletti P Ist Richerche Bio | Chemical compounds,compositions and uses |
| US20050119318A1 (en) * | 2003-10-31 | 2005-06-02 | Hudyma Thomas W. | Inhibitors of HCV replication |
| ES2381890T3 (es) | 2003-12-22 | 2012-06-01 | K.U.Leuven Research & Development | Compuesto de imidazo[4,5-c]piridina y métodos de tratamiento antiviral |
| JP4682155B2 (ja) | 2004-01-21 | 2011-05-11 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | C型肝炎ウイルスに対して活性な大環状ペプチド |
| IN2012DN04853A (enExample) | 2004-02-20 | 2015-09-25 | Boehringer Ingelheim Int | |
| US20070049593A1 (en) | 2004-02-24 | 2007-03-01 | Japan Tobacco Inc. | Tetracyclic fused heterocyclic compound and use thereof as HCV polymerase inhibitor |
| DE602005013922D1 (de) | 2004-02-24 | 2009-05-28 | Japan Tobacco Inc | Kondensierte heterotetracyclische verbindungen und deren verwendung als hcv-polymerase-inhibitor |
| CN1930124A (zh) * | 2004-03-08 | 2007-03-14 | 贝林格尔·英格海姆药物公司 | 制备交叉偶联吲哚的方法 |
| US7126009B2 (en) * | 2004-03-16 | 2006-10-24 | Boehringer Ingelheim International, Gmbh | Palladium catalyzed indolization of 2-bromo or chloroanilines |
| GB0413087D0 (en) * | 2004-06-11 | 2004-07-14 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| US7772271B2 (en) | 2004-07-14 | 2010-08-10 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| US7868037B2 (en) | 2004-07-14 | 2011-01-11 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| US7781478B2 (en) * | 2004-07-14 | 2010-08-24 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| WO2007084413A2 (en) * | 2004-07-14 | 2007-07-26 | Ptc Therapeutics, Inc. | Methods for treating hepatitis c |
| EA200700243A1 (ru) | 2004-07-14 | 2007-08-31 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Способы лечения гепатита с |
| UY29017A1 (es) * | 2004-07-16 | 2006-02-24 | Boehringer Ingelheim Int | Inhibidores de polimerasa viral |
| CA2578636A1 (en) * | 2004-07-22 | 2006-02-23 | Ptc Therapeutics, Inc. | Thienopyridines for treating hepatitis c |
| US7790730B2 (en) | 2004-07-27 | 2010-09-07 | Gilead Sciences, Inc. | Imidazo[4,5-d]pyrimidines, their uses and methods of preparation |
| RU2387655C2 (ru) * | 2004-08-09 | 2010-04-27 | Бристол-Маерс Сквибб Компани | Ингибиторы репликации вируса гепатита с |
| US7153848B2 (en) * | 2004-08-09 | 2006-12-26 | Bristol-Myers Squibb Company | Inhibitors of HCV replication |
| US7659263B2 (en) | 2004-11-12 | 2010-02-09 | Japan Tobacco Inc. | Thienopyrrole compound and use thereof as HCV polymerase inhibitor |
| WO2006076529A1 (en) * | 2005-01-14 | 2006-07-20 | Genelabs Technologies, Inc. | Indole derivatives for treating viral infections |
| RU2466126C2 (ru) | 2005-02-11 | 2012-11-10 | Берингер Ингельхайм Интернациональ Гмбх | Способ получения 2,3-дизамещенных индолов |
| ATE513833T1 (de) | 2005-03-02 | 2011-07-15 | Fibrogen Inc | Thienopyridinverbindungen und verfahren zu ihrer verwendung |
| EP1879885A1 (en) | 2005-05-04 | 2008-01-23 | F. Hoffmann-Roche AG | Heterocyclic antiviral compounds |
| EP2546246A3 (en) | 2005-05-13 | 2013-04-24 | Virochem Pharma Inc. | Compounds and methods for the treatment or prevention of flavivirus infections |
| AU2006261132A1 (en) * | 2005-06-24 | 2006-12-28 | Genelabs Technologies, Inc. | Heteroaryl derivatives for treating viruses |
| WO2007019674A1 (en) | 2005-08-12 | 2007-02-22 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| NZ565496A (en) * | 2005-08-24 | 2010-10-29 | Pfizer | Methods for the preparation of HCV polymerase inhibitors |
| WO2007084435A2 (en) * | 2006-01-13 | 2007-07-26 | Ptc Therapeutics, Inc. | Methods for treating hepatitis c |
| CN101374815B (zh) | 2006-01-27 | 2013-07-17 | 菲布罗根有限公司 | 使低氧诱导因子(hif)稳定的氰基异喹啉化合物 |
| US7816348B2 (en) * | 2006-02-03 | 2010-10-19 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| US20070274951A1 (en) * | 2006-02-09 | 2007-11-29 | Xiao Tong | Combinations comprising HCV protease inhibitor(s) and HCV polymerase inhibitor(s), and methods of treatment related thereto |
| US20090220457A1 (en) * | 2006-03-03 | 2009-09-03 | Lahser Frederick C | Combinations comprising hcv protease inhibitor(s) and hcv ires inhibitor(s), and methods of treatment related thereto |
| KR101084635B1 (ko) | 2006-04-04 | 2011-11-18 | 피브로겐, 인크. | Hif 조절제로서 피롤로- 및 티아졸로-피리딘 화합물 |
| EP1886685A1 (en) | 2006-08-11 | 2008-02-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods, uses and compositions for modulating replication of hcv through the farnesoid x receptor (fxr) activation or inhibition |
| BRPI0716060A2 (pt) | 2006-08-17 | 2013-09-17 | Boehringer Ingelheim Int | inibidores de polimerase viral. |
| JP2010503677A (ja) | 2006-09-15 | 2010-02-04 | シェーリング コーポレイション | 脂質代謝の障害を治療するためのアゼチジノン誘導体 |
| EP2084175B1 (en) | 2006-10-10 | 2010-12-29 | Medivir AB | Hcv nucleoside inhibitor |
| EP2463389A1 (en) | 2006-10-20 | 2012-06-13 | Innogenetics N.V. | Methodology for analysis of sequence variations within the HCV NS5B genomic region |
| EA201101492A1 (ru) | 2006-11-15 | 2012-09-28 | Вирокем Фарма Инк. | Аналоги тиофена для лечения или предупреждения флавивирусных инфекций |
| MX2009006877A (es) | 2006-12-22 | 2009-09-28 | Schering Corp | Derivados indolicos con anillo unido en las posiciones 5,6 y metodos de uso de los mismos. |
| RU2009127855A (ru) | 2006-12-22 | 2011-01-27 | Шеринг Корпорейшн (US) | 4,5 циклоаннелированные производные индола для лечения или предотвращения вируса гепатита с (hcv) и родственных вирусных инфекций |
| CA2673254C (en) | 2006-12-22 | 2013-09-10 | Schering Corporation | 4,5-ring annulated indole derivatives for treating or preventing of hcv and related viral infections |
| AU2008216382A1 (en) * | 2007-02-12 | 2008-08-21 | Array Biopharma, Inc. | Novel inhibitors hepatitis C virus replication |
| US7998951B2 (en) * | 2007-03-05 | 2011-08-16 | Bristol-Myers Squibb Company | HCV NS5B inhibitors |
| JP5211078B2 (ja) | 2007-03-13 | 2013-06-12 | ブリストル−マイヤーズ スクイブ カンパニー | シクロプロピル縮合インドロベンズアゼピンhcvns5b阻害剤 |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| EP2494991A1 (en) | 2007-05-04 | 2012-09-05 | Vertex Pharmaceuticals Incorporated | Combination therapy for the treatment of HCV infection |
| CA2693495A1 (en) * | 2007-08-03 | 2009-02-12 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| EP2188274A4 (en) | 2007-08-03 | 2011-05-25 | Boehringer Ingelheim Int | VIRAL POLYMERASE HEMMER |
| CN101821252A (zh) * | 2007-08-29 | 2010-09-01 | 先灵公司 | 取代的吲哚衍生物及其使用方法 |
| PE20090995A1 (es) | 2007-08-29 | 2009-08-03 | Schering Corp | Derivados indolicos 2,3-sustituidos como inhibidores del virus de la hepatitis c (vhc) |
| PE20090994A1 (es) | 2007-08-29 | 2009-08-03 | Schering Corp | Derivados de azaindol 2,3-sustituidos como agentes antivirales |
| RU2503679C2 (ru) * | 2007-11-15 | 2014-01-10 | Джилид Сайенсиз, Инк. | Ингибиторы репликации вируса иммунодефицита человека |
| WO2009064848A1 (en) * | 2007-11-16 | 2009-05-22 | Schering Corporation | 3-heterocyclic substituted indole derivatives and methods of use thereof |
| WO2009064852A1 (en) * | 2007-11-16 | 2009-05-22 | Schering Corporation | 3-aminosulfonyl substituted indole derivatives and methods of use thereof |
| CA2705338A1 (en) * | 2007-11-16 | 2009-05-22 | Boehringer Ingelheim International Gmbh | Inhibitors of human immunodeficiency virus replication |
| CN101977621A (zh) | 2007-12-05 | 2011-02-16 | 益安药业 | 氟化三肽hcv丝氨酸蛋白酶抑制剂 |
| EA201000948A1 (ru) | 2007-12-19 | 2011-02-28 | Бёрингер Ингельхайм Интернациональ Гмбх | Ингибиторы вирусной полимеразы |
| AU2008339917B2 (en) | 2007-12-24 | 2013-02-07 | Tibotec Pharmaceuticals | Macrocyclic indoles as hepatitis C virus inhibitors |
| US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
| CN102159579B (zh) | 2008-06-13 | 2015-03-25 | 默沙东公司 | 三环吲哚衍生物及其使用方法 |
| TW201006832A (en) | 2008-07-15 | 2010-02-16 | Novartis Ag | Organic compounds |
| PT2331554E (pt) | 2008-08-14 | 2013-05-21 | Janssen R & D Ireland | Derivados de indol macrocíclicos úteis como inibidores do vírus da hepatite c |
| WO2010033443A1 (en) * | 2008-09-17 | 2010-03-25 | Boehringer Ingelheim International Gmbh | Combination of hcv ns3 protease inhibitor with interferon and ribavirin |
| CN105037323A (zh) | 2008-11-14 | 2015-11-11 | 菲布罗根有限公司 | 作为hif羟化酶抑制剂的苯并噻喃衍生物 |
| CN104163816A (zh) | 2008-12-03 | 2014-11-26 | 普雷西迪奥制药公司 | Hcv ns5a的抑制剂 |
| WO2010065681A1 (en) | 2008-12-03 | 2010-06-10 | Presidio Pharmaceuticals, Inc. | Inhibitors of hcv ns5a |
| NZ593647A (en) | 2008-12-23 | 2013-08-30 | Gilead Pharmasset Llc | Synthesis of purine nucleosides |
| JP2012513410A (ja) | 2008-12-23 | 2012-06-14 | アボット・ラボラトリーズ | 抗ウイルス化合物 |
| SG172359A1 (en) | 2008-12-23 | 2011-07-28 | Pharmasset Inc | Nucleoside phosphoramidates |
| US8551973B2 (en) | 2008-12-23 | 2013-10-08 | Gilead Pharmasset Llc | Nucleoside analogs |
| MX2011006332A (es) | 2008-12-23 | 2011-06-27 | Abbott Lab | Compuestos antivirales. |
| MX2011007195A (es) | 2009-01-07 | 2013-07-12 | Scynexis Inc | Derivado de ciclosporina para el uso en el tratamiento de infección de virus de hepatitis c (vhc) y virus de inmunodeficiencia humana (vih). |
| JP2012514657A (ja) | 2009-01-09 | 2012-06-28 | ユニバーシテイ・カレツジ・オブ・カーデイフ・コンサルタンツ・リミテツド | ウィルス感染を治療するためのグアノシンヌクレオシド化合物のホスホルアミダート誘導体 |
| US8314135B2 (en) * | 2009-02-09 | 2012-11-20 | Enanta Pharmaceuticals, Inc. | Linked dibenzimidazole antivirals |
| EP2393359A4 (en) * | 2009-02-09 | 2012-10-03 | Enanta Pharm Inc | COMPOUND DIBENZIMIDAZOLE DERIVATIVES |
| US8188132B2 (en) * | 2009-02-17 | 2012-05-29 | Enanta Pharmaceuticals, Inc. | Linked dibenzimidazole derivatives |
| US8242156B2 (en) * | 2009-02-17 | 2012-08-14 | Enanta Pharmaceuticals, Inc. | Linked dibenzimidazole derivatives |
| US8101643B2 (en) * | 2009-02-27 | 2012-01-24 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
| US8673954B2 (en) | 2009-02-27 | 2014-03-18 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
| US9765087B2 (en) | 2009-02-27 | 2017-09-19 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
| KR20110131312A (ko) | 2009-03-27 | 2011-12-06 | 프레시디오 파마슈티칼스, 인코포레이티드 | 융합된 고리 c형 간염 억제제 |
| JP5913091B2 (ja) * | 2009-03-27 | 2016-04-27 | メルク・シャープ・アンド・ドーム・コーポレーションMerck Sharp & Dohme Corp. | C型肝炎ウイルス複製の阻害剤 |
| US20190127365A1 (en) | 2017-11-01 | 2019-05-02 | Merck Sharp & Dohme Corp. | Inhibitors of hepatitis c virus replication |
| WO2010114896A1 (en) | 2009-03-31 | 2010-10-07 | Arqule, Inc. | Substituted indolo-pyridinone compounds |
| WO2010117935A1 (en) * | 2009-04-06 | 2010-10-14 | Schering Corporation | Compounds and methods for antiviral treatment |
| EP2419404B1 (en) * | 2009-04-15 | 2015-11-04 | AbbVie Inc. | Anti-viral compounds |
| MX2011012155A (es) | 2009-05-13 | 2012-02-28 | Enanta Pharm Inc | Compuestos macrociclicos como inhibidores del virus de hepatitis c. |
| TWI598358B (zh) | 2009-05-20 | 2017-09-11 | 基利法瑪席特有限責任公司 | 核苷磷醯胺 |
| US8618076B2 (en) | 2009-05-20 | 2013-12-31 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
| DK2368890T3 (da) * | 2009-06-11 | 2013-07-22 | Abbvie Bahamas Ltd | Hepatitis C-virusinhibitorer |
| US8716454B2 (en) | 2009-06-11 | 2014-05-06 | Abbvie Inc. | Solid compositions |
| US9394279B2 (en) | 2009-06-11 | 2016-07-19 | Abbvie Inc. | Anti-viral compounds |
| US8937150B2 (en) | 2009-06-11 | 2015-01-20 | Abbvie Inc. | Anti-viral compounds |
| US8609648B2 (en) | 2009-07-02 | 2013-12-17 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US9156818B2 (en) * | 2009-09-11 | 2015-10-13 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8703938B2 (en) * | 2009-09-11 | 2014-04-22 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8759332B2 (en) * | 2009-09-11 | 2014-06-24 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8927709B2 (en) * | 2009-09-11 | 2015-01-06 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8822700B2 (en) * | 2009-09-11 | 2014-09-02 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8815928B2 (en) | 2009-09-11 | 2014-08-26 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| NZ598465A (en) | 2009-10-30 | 2013-10-25 | Boehringer Ingelheim Int | Dosage regimens for hcv combination therapy comprising bi201335, interferon alpha and ribavirin |
| RU2012122637A (ru) | 2009-11-14 | 2013-12-20 | Ф.Хоффманн-Ля Рош Аг | Биомаркеры для прогнозирования быстрого ответа на лечение гепатита с |
| MX2012006026A (es) | 2009-11-25 | 2012-08-15 | Vertex Pharma | Derivados de acido 5-alquinil-tiofen-2-carboxilico y usos para tratamiento o prevencion de infecciones por flavivirus. |
| BR112012011393A2 (pt) | 2009-12-02 | 2017-06-20 | Hoffmann La Roche | biomarcadores para a previsão da resposta sustentada ao tratamento de hcv |
| EP2512480A4 (en) * | 2009-12-14 | 2013-05-15 | Enanta Pharm Inc | HEPATITIS C-VIRUS HEMMER |
| US20130072523A1 (en) | 2009-12-24 | 2013-03-21 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
| PE20130244A1 (es) | 2010-01-25 | 2013-03-10 | Enanta Pharm Inc | Inhibidores del virus de la hepatitis c |
| US8933110B2 (en) | 2010-01-25 | 2015-01-13 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| CN101775003B (zh) * | 2010-02-04 | 2013-12-04 | 银杏树药业(苏州)有限公司 | 苯并噻吩类衍生物及其制备方法和应用 |
| US8623814B2 (en) * | 2010-02-23 | 2014-01-07 | Enanta Pharmaceuticals, Inc. | Antiviral agents |
| US8178531B2 (en) * | 2010-02-23 | 2012-05-15 | Enanta Pharmaceuticals, Inc. | Antiviral agents |
| WO2011109037A1 (en) * | 2010-03-04 | 2011-09-09 | Enanta Pharmaceuticals, Inc. | Combination pharmaceutical agents as inhibitors of hcv replication |
| JP2013522375A (ja) | 2010-03-24 | 2013-06-13 | バーテックス ファーマシューティカルズ インコーポレイテッド | フラビウイルス感染を処置または予防するためのアナログ |
| EP2550268A1 (en) | 2010-03-24 | 2013-01-30 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
| TW201139438A (en) | 2010-03-24 | 2011-11-16 | Vertex Pharma | Analogues for the treatment or prevention of flavivirus infections |
| CN103038237A (zh) | 2010-03-24 | 2013-04-10 | 沃泰克斯药物股份有限公司 | 用于黄病毒感染治疗或预防的类似物 |
| TW201136945A (en) | 2010-03-31 | 2011-11-01 | Pharmasset Inc | Purine nucleoside phosphoramidate |
| JP2013527145A (ja) | 2010-03-31 | 2013-06-27 | ギリード・ファーマセット・エルエルシー | リン含有活性化剤の立体選択的合成 |
| PL3290428T3 (pl) | 2010-03-31 | 2022-02-07 | Gilead Pharmasset Llc | Tabletka zawierająca krystaliczny (S)-2-(((S)-(((2R,3R,4R,5R)-5-(2,4-diokso-3,4-dihydropirymidyn-1(2H)-ylo)-4-fluoro-3-hydroksy-4-metylotetrahydrofuran-2-ylo)metoksy)(fenoksy)fosforylo)amino)propanian izopropylu |
| WO2011127350A1 (en) | 2010-04-09 | 2011-10-13 | Enanta Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
| AR082453A1 (es) | 2010-04-21 | 2012-12-12 | Novartis Ag | Compuestos de furopiridina, composiciones farmaceuticas que los contienen y usos de los mismos |
| CA2800509A1 (en) | 2010-05-24 | 2011-12-01 | Presidio Pharmaceuticals, Inc. | Inhibitors of hcv ns5a |
| GB201012889D0 (en) | 2010-08-02 | 2010-09-15 | Univ Leuven Kath | Antiviral activity of novel bicyclic heterocycles |
| EP2575819A4 (en) | 2010-06-04 | 2013-11-27 | Enanta Pharm Inc | INHIBITORS OF HEPATITIS C VIRUS |
| NZ605440A (en) | 2010-06-10 | 2014-05-30 | Abbvie Bahamas Ltd | Solid compositions comprising an hcv inhibitor |
| WO2011159826A2 (en) | 2010-06-15 | 2011-12-22 | Vertex Pharmaceuticals Incorporated | Hcv ns5b protease mutants |
| WO2012006060A1 (en) | 2010-06-28 | 2012-01-12 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of flavivirus infections |
| WO2012006070A1 (en) | 2010-06-28 | 2012-01-12 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of flavivirus infections |
| JP2013529684A (ja) | 2010-06-28 | 2013-07-22 | バーテックス ファーマシューティカルズ インコーポレイテッド | フラビウイルス感染の処置または予防のための化合物および方法 |
| US8697704B2 (en) | 2010-08-12 | 2014-04-15 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| AR082619A1 (es) | 2010-08-13 | 2012-12-19 | Hoffmann La Roche | Inhibidores del virus de la hepatitis c |
| JP2013534249A (ja) | 2010-08-17 | 2013-09-02 | バーテックス ファーマシューティカルズ インコーポレイテッド | フラビウイルス科ウイルス感染の処置または予防のための化合物および方法 |
| GB201015411D0 (en) | 2010-09-15 | 2010-10-27 | Univ Leuven Kath | Anti-cancer activity of novel bicyclic heterocycles |
| SG188618A1 (en) | 2010-09-21 | 2013-04-30 | Enanta Pharm Inc | Macrocyclic proline derived hcv serine protease inhibitors |
| CA2810928A1 (en) * | 2010-09-22 | 2012-03-29 | Alios Biopharma, Inc. | Substituted nucleotide analogs |
| BR112013007423A2 (pt) | 2010-09-30 | 2016-07-12 | Boehringer Ingelheim Int | terapia combinada no que diz respeito ao tratamento da infecção por hcv |
| US8598183B2 (en) * | 2010-09-30 | 2013-12-03 | Boehringer Ingelheim International Gmbh | Solid state forms of a potent HCV inhibitor |
| SG189985A1 (en) | 2010-10-26 | 2013-06-28 | Presidio Pharmaceuticals Inc | Inhibitors of hepatitis c virus |
| PT3042910T (pt) | 2010-11-30 | 2019-04-16 | Gilead Pharmasset Llc | 2'-espiro-nucleósidos para utilização na terapia da hepatite c |
| EP2658857B1 (en) | 2010-12-29 | 2016-11-02 | Inhibitex, Inc. | Substituted purine nucleosides, phosphoroamidate and phosphorodiamidate derivatives for treatment of viral infections |
| WO2012107589A1 (en) | 2011-02-11 | 2012-08-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment and prevention of hcv infections |
| WO2012123298A1 (en) | 2011-03-11 | 2012-09-20 | F. Hoffmann-La Roche Ag | Antiviral compounds |
| US10201584B1 (en) | 2011-05-17 | 2019-02-12 | Abbvie Inc. | Compositions and methods for treating HCV |
| CN103687489A (zh) | 2011-05-18 | 2014-03-26 | 埃南塔制药公司 | 制备5-氮杂螺[2.4]庚烷-6-甲酸及其衍生物的方法 |
| WO2012175581A1 (en) | 2011-06-24 | 2012-12-27 | F. Hoffmann-La Roche Ag | Antiviral compounds |
| WO2013016499A1 (en) | 2011-07-26 | 2013-01-31 | Vertex Pharmaceuticals Incorporated | Methods for preparation of thiophene compounds |
| TW201317223A (zh) | 2011-07-26 | 2013-05-01 | Vertex Pharma | 噻吩化合物 |
| CA2840242C (en) | 2011-09-16 | 2019-03-26 | Gilead Sciences, Inc. | Methods for treating hcv |
| EP2766365A1 (en) | 2011-10-10 | 2014-08-20 | F.Hoffmann-La Roche Ag | Antiviral compounds |
| US8889159B2 (en) | 2011-11-29 | 2014-11-18 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis C virus |
| BR112014013649A2 (pt) | 2011-12-06 | 2020-10-27 | The Board Of Trustees Of The Leland Stanford Junior University | métodos e agentes para o tratamento de doenças virais e usos dos referidos agentes |
| RU2014127848A (ru) | 2011-12-16 | 2016-02-10 | Ф. Хоффманн-Ля Рош Аг | Ингибиторы hcv ns5a |
| PL2794628T3 (pl) | 2011-12-20 | 2017-09-29 | Riboscience Llc | 4'-azydo-3'-fluoro podstawione pochodne nukleozydów jako inhibitory replikacji RNA HCV |
| US9108999B2 (en) | 2011-12-20 | 2015-08-18 | Riboscience Llc | 2′, 4′-difluoro-2′-methyl substituted nucleoside derivatives as inhibitors of HCV RNA replication |
| CA2860234A1 (en) | 2011-12-22 | 2013-06-27 | Alios Biopharma, Inc. | Substituted phosphorothioate nucleotide analogs |
| US9034832B2 (en) | 2011-12-29 | 2015-05-19 | Abbvie Inc. | Solid compositions |
| WO2013124335A1 (en) | 2012-02-24 | 2013-08-29 | F. Hoffmann-La Roche Ag | Antiviral compounds |
| HK1206362A1 (zh) | 2012-03-21 | 2016-01-08 | Alios Biopharma, Inc. | 硫代氨基磷酸酯核苷酸前藥的固體形式 |
| US9012427B2 (en) | 2012-03-22 | 2015-04-21 | Alios Biopharma, Inc. | Pharmaceutical combinations comprising a thionucleotide analog |
| WO2013147750A1 (en) | 2012-03-27 | 2013-10-03 | Boehringer Ingelheim International Gmbh | Oral combination therapy for treating hcv infection in specific patient sub-population |
| WO2013147749A1 (en) | 2012-03-27 | 2013-10-03 | Boehringer Ingelheim International Gmbh | Oral combination therapy for treating hcv infection in specific patient subgenotype populations |
| US20130261134A1 (en) | 2012-03-30 | 2013-10-03 | Boehringer Ingelheim International Gmbh | Mesylate salt forms of a potent hcv inhibitor |
| US8976594B2 (en) | 2012-05-15 | 2015-03-10 | Micron Technology, Inc. | Memory read apparatus and methods |
| US9064551B2 (en) | 2012-05-15 | 2015-06-23 | Micron Technology, Inc. | Apparatuses and methods for coupling load current to a common source |
| US20140010783A1 (en) | 2012-07-06 | 2014-01-09 | Hoffmann-La Roche Inc. | Antiviral compounds |
| US9064577B2 (en) | 2012-12-06 | 2015-06-23 | Micron Technology, Inc. | Apparatuses and methods to control body potential in memory operations |
| EP2948440B1 (en) | 2013-01-23 | 2017-04-12 | F. Hoffmann-La Roche AG | Antiviral triazole derivatives |
| RU2666144C2 (ru) | 2013-01-24 | 2018-09-06 | Фиброген, Инк. | Кристаллические формы { [1-циано-5-(4-хлорофенокси)-4-гидроксиизохинолин-3-карбонил]-амино} -уксусной кислоты |
| KR20200060782A (ko) | 2013-01-31 | 2020-06-01 | 길리애드 파마셋 엘엘씨 | 두 항바이러스 화합물의 병용 제형물 |
| TW201526899A (zh) | 2013-02-28 | 2015-07-16 | Alios Biopharma Inc | 醫藥組成物 |
| BR112015021429A2 (pt) | 2013-03-05 | 2017-07-18 | Hoffmann La Roche | compostos antivirais |
| WO2014138374A1 (en) | 2013-03-08 | 2014-09-12 | Boehringer Ingelheim International Gmbh | Oral combination therapy for treating hcv infection in specific patient sub-population |
| US11484534B2 (en) | 2013-03-14 | 2022-11-01 | Abbvie Inc. | Methods for treating HCV |
| RU2534613C2 (ru) | 2013-03-22 | 2014-11-27 | Александр Васильевич Иващенко | Алкил 2-{ [(2r,3s,5r)-5-(4-амино-2-оксо-2н-пиримидин-1-ил)- -гидрокси-тетрагидро-фуран-2-илметокси]-фенокси-фосфориламино} -пропионаты, нуклеозидные ингибиторы рнк-полимеразы hcv ns5b, способы их получения и применения |
| BR112015028765A2 (pt) | 2013-05-16 | 2017-07-25 | Riboscience Llc | derivados de nucleosídeo substituído 4'-azido, 3'-desoxi-3'-fluoro |
| US20180200280A1 (en) | 2013-05-16 | 2018-07-19 | Riboscience Llc | 4'-Fluoro-2'-Methyl Substituted Nucleoside Derivatives as Inhibitors of HCV RNA Replication |
| SG11201509424VA (en) | 2013-05-16 | 2015-12-30 | Riboscience Llc | 4'-fluor0-2'-methyl substituted nucleoside derivatives |
| EP3650014B1 (en) | 2013-08-27 | 2021-10-06 | Gilead Pharmasset LLC | Combination formulation of two antiviral compounds |
| GB2518639B (en) | 2013-09-26 | 2016-03-09 | Dyson Technology Ltd | A hand held appliance |
| WO2015103490A1 (en) | 2014-01-03 | 2015-07-09 | Abbvie, Inc. | Solid antiviral dosage forms |
| EA201891620A1 (ru) | 2016-02-05 | 2019-02-28 | Денали Терапьютикс Инк. | Ингибиторы взаимодействующей с рецептором протеинкиназы 1 |
| PL3552017T3 (pl) | 2016-12-09 | 2022-08-08 | Denali Therapeutics Inc. | Związki użyteczne jako inhibitory RIPK1 |
| GB201701087D0 (en) | 2017-01-23 | 2017-03-08 | Univ Leuven Kath | Novel prodrugs of mizoribine |
| US10176880B1 (en) | 2017-07-01 | 2019-01-08 | Intel Corporation | Selective body reset operation for three dimensional (3D) NAND memory |
| AU2018335411B2 (en) | 2017-09-21 | 2024-06-27 | Riboscience Llc | 4'-fluoro-2'-methyl substituted nucleoside derivatives as inhibitors of HCV RNA replication |
| AU2019351912B2 (en) * | 2018-10-02 | 2025-07-31 | Disc Medicine, Inc. | Matriptase 2 inhibitors and uses thereof |
| JP7479486B2 (ja) * | 2020-01-29 | 2024-05-08 | フォグホーン セラピューティクス インコーポレイテッド | 化合物およびその使用 |
| KR102318294B1 (ko) * | 2021-07-15 | 2021-10-26 | 이용화 | 친환경 교면방수제 조성물 및 이를 이용한 방수공법 |
| CA3237199A1 (en) | 2021-11-02 | 2023-05-11 | Flare Therapeutics Inc. | Pparg inverse agonists and uses thereof |
| MX2024008648A (es) | 2022-01-12 | 2024-09-23 | Denali Therapeutics Inc | Formas cristalinas de (s)-5-bencil-n-(5-metil-4-oxo-2,3,4,5-tetrah idropirido [3,2- b][1,4]oxacepin-3-il)-4h-1,2,4-triazol-3-carboxam ida. |
Family Cites Families (160)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1094903A (en) | 1964-03-26 | 1967-12-13 | Smith Kline French Lab | Improvements in or relating to nitrofuran derivatives |
| FR1604809A (en) | 1965-11-26 | 1972-04-17 | Thiazolyl benzimidazoles - animal feed additives | |
| GB1186504A (en) | 1966-10-15 | 1970-04-02 | Fisons Pest Control Ltd | Substituted Heterocyclic Compounds |
| NL6917115A (enExample) | 1968-11-22 | 1970-05-26 | ||
| US3565912A (en) | 1969-01-27 | 1971-02-23 | Upjohn Co | 5-lower-alkanoyl-2,3-bis(p-methoxyphenyl)indoles |
| DE2346316C2 (de) | 1973-09-14 | 1985-02-14 | Bayer Ag, 5090 Leverkusen | Verfahren zur Herstellung von 2-Furylbenzimidazolen |
| GB1521471A (en) | 1974-06-05 | 1978-08-16 | Randall & Son Ltd J | Token-deposit locks |
| FR2291749A1 (fr) | 1974-11-20 | 1976-06-18 | Delalande Sa | Nouveaux benzimidazoles acetiques, leur procede de preparation et leur application en therapeutique |
| US4003908A (en) | 1976-03-11 | 1977-01-18 | E. R. Squibb & Sons, Inc. | Derivatives of imidazo(4,5-b)pyridines |
| CH632628B (de) | 1976-07-26 | Ciba Geigy Ag | Verfahren zur herstellung von benzofuranyl-benzimidazolen und deren verwendung als optische aufheller. | |
| DE2641060A1 (de) | 1976-09-11 | 1978-03-16 | Hoechst Ag | Beta-lactamverbindungen und verfahren zu ihrer herstellung |
| US4264325A (en) | 1977-02-22 | 1981-04-28 | Ciba-Geigy Corporation | Phenyl-benzimidazolyl-furanes for optical brightening of organic materials |
| DE2720111A1 (de) | 1977-05-05 | 1978-11-16 | Agfa Gevaert Ag | Korrosionsschutzmittel fuer zweibad-stabilisatorbaeder |
| DE2964427D1 (en) | 1978-10-04 | 1983-02-03 | Ciba Geigy Ag | Process for the preparation of furanyl-benzazoles |
| ZA795239B (en) * | 1978-10-12 | 1980-11-26 | Glaxo Group Ltd | Heterocyclic compounds |
| DE2852531A1 (de) | 1978-12-05 | 1980-06-19 | Bayer Ag | Benzofuranyl-benzimidazole |
| DE2853765A1 (de) | 1978-12-13 | 1980-06-26 | Bayer Ag | Verfahren zur herstellung von benzimidazolylbenzofuranen |
| DE2904829A1 (de) | 1979-02-08 | 1980-08-14 | Bayer Ag | Verfahren zur herstellung von benzimidazolylbenzofuran |
| US4384121A (en) | 1979-11-01 | 1983-05-17 | Ciba-Geigy Corporation | Cationic fluorescent whitening agents |
| GR75101B (enExample) | 1980-10-23 | 1984-07-13 | Pfizer | |
| GB8707798D0 (en) | 1987-04-01 | 1987-05-07 | Ici Plc | Recovery of metals |
| ZA825413B (en) | 1981-08-26 | 1983-06-29 | Pfizer | Thromboxane synthetase inhibitors, processes for their production, and pharmaceutical compositions comprising them |
| GB2118552A (en) | 1982-04-15 | 1983-11-02 | Pfizer Ltd | Thromboxane synthetase inhibitors |
| JPS60149502A (ja) | 1984-01-12 | 1985-08-07 | Kuraray Co Ltd | インド−ル系農園芸用殺菌剤 |
| US4613990A (en) * | 1984-06-25 | 1986-09-23 | At&T Bell Laboratories | Radiotelephone transmission power control |
| LU85544A1 (fr) | 1984-09-19 | 1986-04-03 | Cird | Derives heterocycliques aromatiques,leur procede de preparation et leur application dans les domaines therapeutique et cosmetique |
| DE3522230A1 (de) | 1985-06-21 | 1987-01-02 | Thomae Gmbh Dr K | Neue 2-arylimidazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| GB8707051D0 (en) | 1986-04-15 | 1987-04-29 | Ici America Inc | Heterocyclic carboxamides |
| GB8609175D0 (en) * | 1986-04-15 | 1986-05-21 | Ici America Inc | Heterocyclic carboxamides |
| US4859684A (en) | 1986-09-15 | 1989-08-22 | Janssen Pharmaceutica N.V. | (1H-imidazol-1-ylmethyl) substituted benzimidazole derivatives and use thereof in treating androgen dependent disorders |
| US4957932A (en) | 1987-11-25 | 1990-09-18 | Merck Frosst Canada, Inc. | Benzoheterazoles |
| JP2700475B2 (ja) | 1988-07-30 | 1998-01-21 | コニカ株式会社 | 非線形光学材料および非線形光学素子 |
| JPH03157646A (ja) | 1989-11-15 | 1991-07-05 | Konica Corp | ハロゲン化銀写真感光材料 |
| JPH03219232A (ja) | 1990-01-24 | 1991-09-26 | Konica Corp | 分光増感されたハロゲン化銀写真感光材料 |
| EP0525129A4 (en) | 1990-04-13 | 1993-03-24 | Smith-Kline Beecham Corporation | Substituted benzimidazoles |
| JP2909645B2 (ja) | 1990-05-28 | 1999-06-23 | コニカ株式会社 | ハロゲン化銀カラー写真感光材料 |
| DE69131021T2 (de) | 1990-12-14 | 1999-08-12 | Smithkline Beecham Corp., Philadelphia, Pa. 19101 | Angiotensin-ii-rezeptor blockierende zusammensetzungen |
| US5527819A (en) | 1991-09-06 | 1996-06-18 | Merck & Co., Inc. | Inhibitors of HIV reverse transcriptase |
| PT100905A (pt) | 1991-09-30 | 1994-02-28 | Eisai Co Ltd | Compostos heterociclicos azotados biciclicos contendo aneis de benzeno, ciclo-hexano ou piridina e de pirimidina, piridina ou imidazol substituidos e composicoes farmaceuticas que os contem |
| GB9121463D0 (en) | 1991-10-10 | 1991-11-27 | Smithkline Beecham Corp | Medicament |
| GB9122590D0 (en) | 1991-10-24 | 1991-12-04 | Lilly Industries Ltd | Pharmaceutical compounds |
| JPH05165163A (ja) | 1991-12-11 | 1993-06-29 | Konica Corp | 色素画像形成方法 |
| JP3013124B2 (ja) | 1991-12-26 | 2000-02-28 | コニカ株式会社 | カラー画像形成方法 |
| US5216003A (en) | 1992-01-02 | 1993-06-01 | G. D. Searle & Co. | Diacid-containing benzimidazole compounds for treatment of neurotoxic injury |
| GB9203798D0 (en) * | 1992-02-21 | 1992-04-08 | Fujisawa Pharmaceutical Co | Quinolylbenzofuran derivatives,processes for preparation thereof and pharmaceutical composition comprising the same |
| US5314796A (en) | 1992-04-02 | 1994-05-24 | Konica Corporation | Silver halide color photographic light sensitive material |
| US5387600A (en) | 1992-07-30 | 1995-02-07 | Fuji Photo Film Co., Ltd. | Treating arteriosclerosis using benzimidazole compositions |
| DE4237617A1 (de) | 1992-11-06 | 1994-05-11 | Bayer Ag | Verwendung von substituierten Benzimidazolen |
| DE4237557A1 (de) | 1992-11-06 | 1994-05-11 | Bayer Ag | Substituierte Benzimidazole |
| EP0672031B1 (en) | 1992-12-02 | 2003-03-12 | Pfizer Inc. | Catechol diethers as selective pde iv inhibitors |
| JP3213426B2 (ja) * | 1993-02-19 | 2001-10-02 | エーザイ株式会社 | 6,7−ジヒドロ−5H−シクロペンタ〔d〕ピリミジン誘導体 |
| DE69434016T2 (de) | 1993-03-04 | 2005-02-10 | Fuji Photo Film Co., Ltd., Minami-Ashigara | Photographisches Silberhalogenidmaterial |
| DE4309969A1 (de) | 1993-03-26 | 1994-09-29 | Bayer Ag | Substituierte heteroanellierte Imidazole |
| US6169107B1 (en) * | 1993-04-28 | 2001-01-02 | Sumitomo Pharmaceutical Co., Ltd. | Indoloylguanidine derivatives |
| JP3156444B2 (ja) | 1993-06-02 | 2001-04-16 | 松下電器産業株式会社 | 短波長レーザ光源およびその製造方法 |
| DE4330959A1 (de) | 1993-09-09 | 1995-03-16 | Schering Ag | Neue Benzimidazolderivate, Verfahren zu ihrer Herstellung und ihre pharmazeutische Verwendung |
| ES2157268T5 (es) | 1994-02-24 | 2004-12-01 | SYMRISE GMBH & CO KG | Preparados cosmeticos y dermatologicos que contienen acidos fenilen-1,4-bisbencimidazolsulfonicos. |
| CA2124169A1 (en) | 1994-05-24 | 1995-11-25 | Richard Mcculloch Keenan | Chemical compounds |
| EP0763026B1 (en) | 1994-05-27 | 2003-03-26 | James Black Foundation Limited | Gastrin and cck antagonists |
| PT801059E (pt) | 1994-11-29 | 2001-10-30 | Dainippon Pharmaceutical Co | Derivado indol |
| EP0717143A1 (de) | 1994-12-16 | 1996-06-19 | Lignozym GmbH | Mehrkomponentensystem zum Verändern, Abbau oder Bleichen von Lignin, ligninhaltigen Materialien oder ähnlichen Stoffen sowie Verfahren zu seiner Anwendung |
| DE19507913C2 (de) | 1995-03-07 | 1998-04-16 | Agfa Gevaert Ag | Farbfotografisches Silberhalogenidmaterial |
| WO1996032379A1 (en) | 1995-04-10 | 1996-10-17 | Fujisawa Pharmaceutical Co., Ltd. | INDOLE DERIVATIVES AS cGMP-PDE INHIBITORS |
| CN1187812A (zh) * | 1995-04-10 | 1998-07-15 | 藤泽药品工业株式会社 | 作为环状乌苷3',5'-一磷酸盐磷酸二酯酶抑制剂的吲哚衍生物 |
| US6444694B1 (en) | 1995-06-06 | 2002-09-03 | Wyeth | Styryl benzimidazole derivatives |
| JP3544245B2 (ja) | 1995-06-09 | 2004-07-21 | 富士写真フイルム株式会社 | ハロゲン化銀カラー写真感光材料の処理方法 |
| WO1997006141A1 (en) | 1995-08-04 | 1997-02-20 | Otsuka Kagaku Kabushiki Kaisha | Indole-2-carboxylic ester derivatives and agricultural and horticultural bacteriocides containing the same as the active ingredient |
| US5950124A (en) * | 1995-09-06 | 1999-09-07 | Telxon Corporation | Cellular communication system with dynamically modified data transmission parameters |
| WO1997012613A1 (en) | 1995-10-05 | 1997-04-10 | Warner-Lambert Company | Method for treating and preventing inflammation and atherosclerosis |
| US6063806A (en) * | 1995-10-05 | 2000-05-16 | Kyoto Pharmaceutical Industries, Ltd. | Indolyl or indolinyl derivatives and medicinal use thereof as ACAT or lipid peroxidation inhibitors |
| JPH09124632A (ja) | 1995-10-31 | 1997-05-13 | Sankyo Co Ltd | ベンゾヘテロ環誘導体 |
| CA2241186C (en) | 1995-12-28 | 2006-02-14 | Fujisawa Pharmaceutical Co., Ltd. | Benzimidazole derivatives |
| US5850592A (en) * | 1996-01-11 | 1998-12-15 | Gte Internetworking Incorporated | Method for self-organizing mobile wireless station network |
| JP2803626B2 (ja) * | 1996-04-05 | 1998-09-24 | 日本電気株式会社 | 移動無線端末の送信電力制御方式 |
| GB9610811D0 (en) | 1996-05-23 | 1996-07-31 | Pharmacia Spa | Combinatorial solid phase synthesis of a library of indole derivatives |
| WO1997048697A1 (en) | 1996-06-19 | 1997-12-24 | Rhone-Poulenc Rorer Limited | Substituted azabicylic compounds and their use as inhibitors of the production of tnf and cyclic amp phosphodiesterase |
| GB9614347D0 (en) | 1996-07-09 | 1996-09-04 | Smithkline Beecham Spa | Novel compounds |
| AUPO118896A0 (en) | 1996-07-23 | 1996-08-15 | Fujisawa Pharmaceutical Co., Ltd. | New use |
| CA2263566C (en) | 1996-08-28 | 2003-09-09 | Pfizer Inc. | Substituted 6,5-hetero-bicyclic derivatives |
| JPH10114654A (ja) | 1996-10-09 | 1998-05-06 | Fujisawa Pharmaceut Co Ltd | 新規用途 |
| EP0949259B1 (en) * | 1996-12-26 | 2001-06-20 | Nikken Chemicals Company, Limited | N-hydroxyurea derivatives and medicinal compositions containing the same |
| JPH10204059A (ja) | 1997-01-22 | 1998-08-04 | Ono Pharmaceut Co Ltd | フェニルスルホンアミド誘導体 |
| DK0968206T3 (da) | 1997-02-19 | 2007-03-26 | Berlex Inc | N-heterocykliske derivater som NOS-inhibitorer |
| WO1998037069A1 (en) | 1997-02-20 | 1998-08-27 | Shionogi & Co., Ltd. | Indole dicarboxylic acid derivatives |
| US6089156A (en) * | 1997-03-21 | 2000-07-18 | Heidelberger Druckmaschinen Aktiengesellschaft | Turning device for a printing press |
| US5932743A (en) * | 1997-08-21 | 1999-08-03 | American Home Products Corporation | Methods for the solid phase synthesis of substituted indole compounds |
| DE19753522A1 (de) | 1997-12-03 | 1999-06-10 | Boehringer Ingelheim Pharma | Substituierte Indole, ihre Herstellung und ihre Verwendung als Arzneimittel |
| SE9704544D0 (sv) | 1997-12-05 | 1997-12-05 | Astra Pharma Prod | Novel compounds |
| SE9704545D0 (sv) | 1997-12-05 | 1997-12-05 | Astra Pharma Prod | Novel compounds |
| EP1037974B1 (en) | 1997-12-11 | 2007-10-03 | SmithKline Beecham Corporation | Hepatitis c virus ns5b truncated protein and methods thereof to identify antiviral compounds |
| JPH11177218A (ja) | 1997-12-12 | 1999-07-02 | Tamura Kaken Co Ltd | 電子回路用金属面具備部品及びその表面保護剤 |
| US6104512A (en) * | 1998-01-23 | 2000-08-15 | Motorola, Inc. | Method for adjusting the power level of an infrared signal |
| KR100291413B1 (ko) * | 1998-03-02 | 2001-07-12 | 김영환 | 이동통신단말기의송신전력제어장치 |
| CZ20004351A3 (cs) | 1998-05-22 | 2001-10-17 | Avanir Pharmaceuticals | Benzimidazolová analoga pro sniľování hladiny IgE |
| US6232320B1 (en) | 1998-06-04 | 2001-05-15 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| KR100597913B1 (ko) | 1998-06-18 | 2006-07-10 | 노파르티스 아게 | 벤즈아졸 화합물 및 그의 용도 |
| US7223879B2 (en) | 1998-07-10 | 2007-05-29 | Massachusetts Institute Of Technology | Ligands for metals and improved metal-catalyzed processes based thereon |
| US6228868B1 (en) * | 1998-07-27 | 2001-05-08 | Abbott Laboratories | Oxazoline antiproliferative agents |
| AU756627B2 (en) | 1998-07-27 | 2003-01-16 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Diketoacid-derivatives as inhibitors of polymerases |
| AU5227999A (en) | 1998-07-27 | 2000-02-21 | Abbott Laboratories | Substituted oxazolines as antiproliferative agents |
| IL141456A0 (en) | 1998-08-21 | 2002-03-10 | Viropharma Inc | Rhodanine derivatives and pharmaceutical compositions containing the same |
| CN1324250A (zh) | 1998-09-04 | 2001-11-28 | 维洛药品公司 | 治疗或预防病毒感染及其所致疾病的方法 |
| WO2000018231A1 (en) | 1998-09-25 | 2000-04-06 | Viropharma Incorporated | Methods for treating or preventing viral infections and associated diseases |
| GB9823871D0 (en) | 1998-10-30 | 1998-12-23 | Pharmacia & Upjohn Spa | 2-Amino-thiazole derivatives, process for their preparation, and their use as antitumour agents |
| US6531475B1 (en) | 1998-11-12 | 2003-03-11 | Neurocrine Biosciences, Inc. | CRF receptor antagonists and methods relating thereto |
| EP1129091B1 (en) | 1998-11-12 | 2002-10-02 | Neurocrine Biosciences, Inc. | Crf receptor antagonists and methods relating thereto |
| US6358992B1 (en) | 1998-11-25 | 2002-03-19 | Cell Pathways, Inc. | Method of inhibiting neoplastic cells with indole derivatives |
| US6869950B1 (en) | 1998-12-24 | 2005-03-22 | Fujisawa Pharmaceutical Co., Ltd. | Benzimidazole derivatives |
| ES2197092T3 (es) * | 1999-04-02 | 2004-01-01 | Bristol-Myers Squibb Pharma Company | Sulfonil arilos como inhibidores del factor xa. |
| DE19951360A1 (de) | 1999-10-26 | 2001-05-03 | Aventis Pharma Gmbh | Substituierte Indole |
| JP2001122855A (ja) | 1999-10-27 | 2001-05-08 | Japan Tobacco Inc | インドール化合物及びその医薬用途 |
| US6346493B1 (en) * | 1999-10-27 | 2002-02-12 | Ferro Corporation | Decorative glass enamels |
| NL1013456C2 (nl) * | 1999-11-02 | 2001-05-03 | Dsm Nv | Kristallijn melamine en de toepassing in aminoformaldehydeharsen. |
| US6455525B1 (en) * | 1999-11-04 | 2002-09-24 | Cephalon, Inc. | Heterocyclic substituted pyrazolones |
| IL150388A0 (en) | 1999-12-24 | 2002-12-01 | Aventis Pharma Ltd | Azaindoles |
| SK13752001A3 (sk) | 1999-12-27 | 2002-07-02 | Japan Tobacco, Inc. | Zlúčeniny s fúzovanými kruhmi a ich použitie ako liečiv |
| US6770666B2 (en) | 1999-12-27 | 2004-08-03 | Japan Tobacco Inc. | Fused-ring compounds and use thereof as drugs |
| HUP0203897A3 (en) | 1999-12-28 | 2005-06-28 | Pfizer Prod Inc | Non-peptidyl inhibitors of vla-4 dependent cell binding useful in treating inflammatory, autoimmune, and respiratory diseases |
| GB0003397D0 (en) | 2000-02-14 | 2000-04-05 | Merck Sharp & Dohme | Therapeutic agents |
| AU2001261377A1 (en) | 2000-05-10 | 2001-11-20 | Smith Kline Beecham Corporation | Novel anti-infectives |
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| US6448281B1 (en) | 2000-07-06 | 2002-09-10 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
| GB0017676D0 (en) | 2000-07-19 | 2000-09-06 | Angeletti P Ist Richerche Bio | Inhibitors of viral polymerase |
| US6940392B2 (en) * | 2001-04-24 | 2005-09-06 | Savi Technology, Inc. | Method and apparatus for varying signals transmitted by a tag |
| US6765484B2 (en) * | 2000-09-07 | 2004-07-20 | Savi Technology, Inc. | Method and apparatus for supplying commands to a tag |
| HUP0400726A3 (en) | 2001-01-22 | 2007-05-29 | Merck & Co Inc | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| GB0102109D0 (en) | 2001-01-26 | 2001-03-14 | Syngenta Ltd | Chemical process |
| WO2002069903A2 (en) | 2001-03-06 | 2002-09-12 | Biocryst Pharmaceuticals, Inc. | Nucleosides, preparation thereof and use as inhibitors of rna viral polymerases |
| CA2439176A1 (en) | 2001-03-08 | 2002-09-12 | Boehringer Ingelheim (Canada) Ltd. | Assay for identifying inhibitors of the rna dependent rna polymerase (ns5b) of hcv |
| EP1256628A3 (en) | 2001-05-10 | 2003-03-19 | Agouron Pharmaceuticals, Inc. | Hepatitis c virus (hcv) ns5b rna polymerase and mutants thereof |
| AR036081A1 (es) | 2001-06-07 | 2004-08-11 | Smithkline Beecham Corp | Compuesto de 1,2-dihidroquinolina, su uso para preparar una composicion farmaceutica, metodos para prepararlo y compuestos del acido 2-aminobenzoico n-alquilado de utilidad como intermediarios en dichos metodos |
| EP1395571A1 (en) | 2001-06-11 | 2004-03-10 | Shire Biochem Inc. | Compounds and methods for the treatment or prevention of flavivirus infections |
| PL395097A1 (pl) | 2001-06-11 | 2011-10-10 | Vertex Pharmaceuticals (Canada) Incorporated | Sposób wytwarzania związku o wzorze A stanowiącego pochodną tiofenu |
| GB0115109D0 (en) | 2001-06-21 | 2001-08-15 | Aventis Pharma Ltd | Chemical compounds |
| JP2003212846A (ja) * | 2001-06-26 | 2003-07-30 | Japan Tobacco Inc | 縮合環化合物及びc型肝炎治療剤 |
| AR035543A1 (es) | 2001-06-26 | 2004-06-16 | Japan Tobacco Inc | Agente terapeutico para la hepatitis c que comprende un compuesto de anillo condensado, compuesto de anillo condensado, composicion farmaceutica que lo comprende, compuestos de benzimidazol, tiazol y bifenilo utiles como intermediarios para producir dichos compuestos, uso del compuesto de anillo con |
| CA2448737C (en) | 2001-07-20 | 2010-06-01 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
| EP2335700A1 (en) | 2001-07-25 | 2011-06-22 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis C virus polymerase inhibitors with a heterobicylic structure |
| US7294457B2 (en) | 2001-08-07 | 2007-11-13 | Boehringer Ingelheim (Canada) Ltd. | Direct binding assay for identifying inhibitors of HCV polymerase |
| IL160043A0 (en) | 2001-08-22 | 2004-06-20 | Ciba Sc Holding Ag | Process for the preparation of indole derivatives |
| WO2003026587A2 (en) | 2001-09-26 | 2003-04-03 | Bristol-Myers Squibb Company | Compounds useful for treating hepatitus c virus |
| UA79248C2 (en) | 2001-11-09 | 2007-06-11 | Janssen Pharmaceutica Nv | Mandelate salts of substituted tetracyclic tetrahydrofuran derivatives |
| CA2487211C (en) | 2002-06-04 | 2010-09-14 | Neogenesis Pharmaceuticals, Inc. | Pyrazolo(1,5a) pyrimidine compounds as antiviral agents |
| GB0215293D0 (en) | 2002-07-03 | 2002-08-14 | Rega Foundation | Viral inhibitors |
| US7223785B2 (en) | 2003-01-22 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| US7098231B2 (en) | 2003-01-22 | 2006-08-29 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| US7286844B1 (en) * | 2003-01-31 | 2007-10-23 | Bbn Technologies Corp. | Systems and methods for three dimensional antenna selection and power control in an Ad-Hoc wireless network |
| GB0307891D0 (en) | 2003-04-04 | 2003-05-14 | Angeletti P Ist Richerche Bio | Chemical compounds,compositions and uses |
| CN1829709A (zh) | 2003-08-01 | 2006-09-06 | 健亚生物科技公司 | 对抗黄病毒的双环咪唑衍生物 |
| WO2005014543A1 (ja) | 2003-08-06 | 2005-02-17 | Japan Tobacco Inc. | 縮合環化合物及びそのhcvポリメラーゼ阻害剤としての利用 |
| US7136667B2 (en) * | 2003-10-28 | 2006-11-14 | Nokia Corporation | Method and radio terminal equipment arrangement for power control, radio terminal equipment and secondary terminal unit |
| US7212122B2 (en) * | 2003-12-30 | 2007-05-01 | G2 Microsystems Pty. Ltd. | Methods and apparatus of meshing and hierarchy establishment for tracking devices |
| IN2012DN04853A (enExample) * | 2004-02-20 | 2015-09-25 | Boehringer Ingelheim Int | |
| CN1930124A (zh) | 2004-03-08 | 2007-03-14 | 贝林格尔·英格海姆药物公司 | 制备交叉偶联吲哚的方法 |
| US7126009B2 (en) | 2004-03-16 | 2006-10-24 | Boehringer Ingelheim International, Gmbh | Palladium catalyzed indolization of 2-bromo or chloroanilines |
| US7348875B2 (en) * | 2004-05-04 | 2008-03-25 | Battelle Memorial Institute | Semi-passive radio frequency identification (RFID) tag with active beacon |
| UY29017A1 (es) | 2004-07-16 | 2006-02-24 | Boehringer Ingelheim Int | Inhibidores de polimerasa viral |
| US7342497B2 (en) * | 2004-08-26 | 2008-03-11 | Avante International Technology, Inc | Object monitoring, locating, and tracking system employing RFID devices |
| US7319397B2 (en) * | 2004-08-26 | 2008-01-15 | Avante International Technology, Inc. | RFID device for object monitoring, locating, and tracking |
| RU2466126C2 (ru) | 2005-02-11 | 2012-11-10 | Берингер Ингельхайм Интернациональ Гмбх | Способ получения 2,3-дизамещенных индолов |
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