ES2289161T3 - Derivados de 4-(heteroaril de 6 miembros)-acil pirrolidina como inhibidores de hcv. - Google Patents
Derivados de 4-(heteroaril de 6 miembros)-acil pirrolidina como inhibidores de hcv. Download PDFInfo
- Publication number
- ES2289161T3 ES2289161T3 ES02783059T ES02783059T ES2289161T3 ES 2289161 T3 ES2289161 T3 ES 2289161T3 ES 02783059 T ES02783059 T ES 02783059T ES 02783059 T ES02783059 T ES 02783059T ES 2289161 T3 ES2289161 T3 ES 2289161T3
- Authority
- ES
- Spain
- Prior art keywords
- tert
- rel
- pyrrolidine
- isobutyl
- pyrazin
- 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
Links
- 239000003112 inhibitor Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 235
- 125000003118 aryl group Chemical group 0.000 claims abstract description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 48
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 44
- 239000001257 hydrogen Substances 0.000 claims abstract description 37
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 36
- 125000005843 halogen group Chemical group 0.000 claims abstract description 23
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 21
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 21
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 19
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 16
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 14
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 13
- 125000004429 atom Chemical group 0.000 claims abstract description 12
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 8
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- -1 methoxy, ethoxy Chemical group 0.000 claims description 189
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 152
- 239000002253 acid Substances 0.000 claims description 76
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 68
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 66
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- 238000006243 chemical reaction Methods 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 22
- 208000015181 infectious disease Diseases 0.000 claims description 18
- 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 description 15
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 15
- 150000002148 esters Chemical class 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 239000012453 solvate Substances 0.000 claims description 13
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 150000001721 carbon Chemical group 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- YCYHUIIAAJRRSG-UEOVABOPSA-N (2s,4r,5r)-1-(4-tert-butyl-3-methoxybenzoyl)-2-(2-methylpropyl)-4-pyrazin-2-yl-5-pyridin-2-ylpyrrolidine-2-carboxylic acid Chemical compound C1=C(C(C)(C)C)C(OC)=CC(C(=O)N2[C@](C[C@H]([C@@H]2C=2N=CC=CC=2)C=2N=CC=NC=2)(CC(C)C)C(O)=O)=C1 YCYHUIIAAJRRSG-UEOVABOPSA-N 0.000 claims description 4
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- SCSFDIAEMPZBQC-RFQXOUTQSA-N (2s,4s,5r)-1-(4-tert-butyl-3-methoxybenzoyl)-2-(2-methylpropyl)-5-phenyl-4-pyrazin-2-ylpyrrolidine-2-carboxylic acid Chemical compound C1=C(C(C)(C)C)C(OC)=CC(C(=O)N2[C@](C[C@@H]([C@@H]2C=2C=CC=CC=2)C=2N=CC=NC=2)(CC(C)C)C(O)=O)=C1 SCSFDIAEMPZBQC-RFQXOUTQSA-N 0.000 claims description 3
- GNSGYACMPIKXRD-UQEHLFEPSA-N (2s,4s,5r)-1-(4-tert-butylbenzoyl)-2-(2-methylpropyl)-5-(3-phenylphenyl)-4-pyrazin-2-ylpyrrolidine-2-carboxylic acid Chemical compound N1([C@H]([C@H](C[C@@]1(CC(C)C)C(O)=O)C=1N=CC=NC=1)C=1C=C(C=CC=1)C=1C=CC=CC=1)C(=O)C1=CC=C(C(C)(C)C)C=C1 GNSGYACMPIKXRD-UQEHLFEPSA-N 0.000 claims description 3
- WCIJZKBEXNTWDT-QVNGGLPSSA-N (2s,4s,5r)-1-(4-tert-butylbenzoyl)-2-(2-methylpropyl)-5-phenyl-4-pyrazin-2-ylpyrrolidine-2-carboxylic acid Chemical compound N1([C@H]([C@H](C[C@@]1(CC(C)C)C(O)=O)C=1N=CC=NC=1)C=1C=CC=CC=1)C(=O)C1=CC=C(C(C)(C)C)C=C1 WCIJZKBEXNTWDT-QVNGGLPSSA-N 0.000 claims description 3
- QZUFUCKBIUIAOE-LNGZGTQPSA-N (2s,4s,5r)-1-(4-tert-butylbenzoyl)-5-[4-(dimethylamino)phenyl]-2-(2-methylpropyl)-4-pyrazin-2-ylpyrrolidine-2-carboxylic acid Chemical compound N1([C@H]([C@H](C[C@@]1(CC(C)C)C(O)=O)C=1N=CC=NC=1)C=1C=CC(=CC=1)N(C)C)C(=O)C1=CC=C(C(C)(C)C)C=C1 QZUFUCKBIUIAOE-LNGZGTQPSA-N 0.000 claims description 3
- XIBOBBKUBBCSQQ-DCLXLUIPSA-N (4-tert-butyl-3-methoxyphenyl)-[(2R,3S,5S)-5-(2-methylpropyl)-3-pyrazin-2-yl-2-(1,3-thiazol-2-yl)pyrrolidin-1-yl]methanone Chemical compound C(C)(C)(C)C1=C(C=C(C(=O)N2[C@H](C[C@@H]([C@@H]2C=2SC=CN=2)C2=NC=CN=C2)CC(C)C)C=C1)OC XIBOBBKUBBCSQQ-DCLXLUIPSA-N 0.000 claims description 3
- 125000003287 1H-imidazol-4-ylmethyl group Chemical group [H]N1C([H])=NC(C([H])([H])[*])=C1[H] 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 3
- 238000013160 medical therapy Methods 0.000 claims description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 3
- 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 claims description 2
- 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 claims description 2
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 claims description 2
- 230000010933 acylation Effects 0.000 claims description 2
- 238000005917 acylation reaction Methods 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 2
- 125000006513 pyridinyl methyl group Chemical group 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- BUZOXXIITIRFRK-IAKTWSEQSA-N (2s,4s,5s)-1-(4-tert-butyl-3-methoxybenzoyl)-5-methyl-2-(2-methylpropyl)-4-pyrazin-2-ylpyrrolidine-2-carboxylic acid Chemical compound C1=C(C(C)(C)C)C(OC)=CC(C(=O)N2[C@](C[C@@H]([C@@H]2C)C=2N=CC=NC=2)(CC(C)C)C(O)=O)=C1 BUZOXXIITIRFRK-IAKTWSEQSA-N 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 4
- 125000001054 5 membered carbocyclic group Chemical group 0.000 abstract 1
- 125000004008 6 membered carbocyclic group Chemical group 0.000 abstract 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 80
- 239000007787 solid Substances 0.000 description 66
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 60
- 239000003480 eluent Substances 0.000 description 51
- 239000000203 mixture Substances 0.000 description 50
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 239000002904 solvent Substances 0.000 description 38
- 238000005481 NMR spectroscopy Methods 0.000 description 37
- 241000711549 Hepacivirus C Species 0.000 description 31
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 30
- 235000019253 formic acid Nutrition 0.000 description 30
- 239000000047 product Substances 0.000 description 30
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
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- 239000000243 solution Substances 0.000 description 25
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
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- CAEAGGWLZXCUFO-UHFFFAOYSA-N tert-butyl 4-methyl-2-(1,3-thiazol-4-ylmethylideneamino)pentanoate Chemical compound CC(C)(C)OC(=O)C(CC(C)C)N=CC1=CSC=N1 CAEAGGWLZXCUFO-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- C07D401/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- 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
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D417/14—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 three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Virology (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0126440A GB0126440D0 (en) | 2001-11-02 | 2001-11-02 | Compounds |
| GB0126440 | 2001-11-02 | ||
| GB0203900A GB0203900D0 (en) | 2002-02-19 | 2002-02-19 | Compounds |
| GB0203900 | 2002-02-19 | ||
| GB0219321A GB0219321D0 (en) | 2002-08-19 | 2002-08-19 | Compounds |
| GB0219321 | 2002-08-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2289161T3 true ES2289161T3 (es) | 2008-02-01 |
Family
ID=27256312
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02783059T Expired - Lifetime ES2289161T3 (es) | 2001-11-02 | 2002-10-30 | Derivados de 4-(heteroaril de 6 miembros)-acil pirrolidina como inhibidores de hcv. |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US7259163B2 (https=) |
| EP (1) | EP1440069B1 (https=) |
| JP (1) | JP2005515172A (https=) |
| AR (1) | AR037182A1 (https=) |
| AT (1) | ATE370137T1 (https=) |
| DE (1) | DE60221875T2 (https=) |
| ES (1) | ES2289161T3 (https=) |
| TW (1) | TW200302823A (https=) |
| WO (1) | WO2003037895A1 (https=) |
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| GB0211418D0 (en) * | 2002-05-17 | 2002-06-26 | Glaxo Group Ltd | Compounds |
| ES2320771T3 (es) | 2003-04-16 | 2009-05-28 | Bristol-Myers Squibb Company | Inhibidores peptidicos de isoquinolina macrociclicos del virus de la hepatitis c. |
| HRP20130971T1 (hr) | 2004-02-20 | 2013-11-08 | Boehringer Ingelheim International Gmbh | Inhibitori virusne polimeraze |
| JP2007530516A (ja) * | 2004-03-26 | 2007-11-01 | スミスクライン・ビーチャム・コーポレイション | 抗ウイルス剤として有用な４−カルボキシピラゾール誘導体 |
| GB0423672D0 (en) * | 2004-10-25 | 2004-11-24 | Glaxo Group Ltd | Compounds |
| GB0519485D0 (en) * | 2005-09-23 | 2005-11-02 | Glaxo Group Ltd | Compounds |
| GB0519478D0 (en) * | 2005-09-23 | 2005-11-02 | Glaxo Group Ltd | Compounds |
| GB0519486D0 (en) * | 2005-09-23 | 2005-11-02 | Glaxo Group Ltd | Compounds |
| WO2007039146A1 (en) * | 2005-09-23 | 2007-04-12 | Smithkline Beecham Corporation | 4-carboxy pyrazole derivatives as anti-viral agents |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| WO2009003009A1 (en) * | 2007-06-26 | 2008-12-31 | Enanta Pharmaceuticals, Inc. | Substituted pyrrolidine as anti-infectives |
| US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
| WO2010065668A1 (en) | 2008-12-03 | 2010-06-10 | Presidio Pharmaceuticals, Inc. | Inhibitors of hcv ns5a |
| SI2373172T1 (sl) | 2008-12-03 | 2013-12-31 | Presidio Pharmaceuticals, Inc. | Inhibitorji HCV NS5A |
| SG194404A1 (en) | 2008-12-23 | 2013-11-29 | Gilead Pharmasset Llc | Synthesis of purine nucleosides |
| KR20110098849A (ko) | 2008-12-23 | 2011-09-01 | 파마셋 인코포레이티드 | 뉴클레오시드 유사체 |
| PT2376088T (pt) | 2008-12-23 | 2017-05-02 | Gilead Pharmasset Llc | Fosforamidatos de nucleósidos de 2-amino-purina 6-osubstituída |
| SG174883A1 (en) | 2009-03-27 | 2011-11-28 | Presidio Pharmaceuticals Inc | Fused ring inhibitors of hepatitis c |
| US8618076B2 (en) | 2009-05-20 | 2013-12-31 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
| 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 |
| WO2011073376A1 (en) | 2009-12-18 | 2011-06-23 | Euroscreen S.A. | Pyrrolidine or thiazolidine carboxylic acid derivatives, pharmaceutical composition and methods for use in treating metabolic disordersas as agonists of g- protein coupled receptor 43 (gpr43) |
| PT2609923T (pt) | 2010-03-31 | 2017-08-30 | Gilead Pharmasset Llc | Processo para a cristalização de 2-(((s)- (perfluorofenoxi)(fenoxi)fosforil)amino)propanoato de (s)-isopropilo |
| UY33312A (es) | 2010-03-31 | 2011-10-31 | Pharmasset Inc | Fosforamidato de nucleosido de purina |
| CA2800509A1 (en) | 2010-05-24 | 2011-12-01 | Presidio Pharmaceuticals, Inc. | Inhibitors of hcv ns5a |
| WO2012020036A1 (en) | 2010-08-13 | 2012-02-16 | F. Hoffmann-La Roche Ag | Hepatitis c virus inhibitors |
| MX2013004655A (es) | 2010-10-26 | 2013-08-27 | Presidio Pharmaceuticals Inc | Inhibidores del virus de la hepatitis c. |
| AU2011336632B2 (en) | 2010-11-30 | 2015-09-03 | Gilead Pharmasset Llc | Compounds |
| WO2012123298A1 (en) | 2011-03-11 | 2012-09-20 | F. Hoffmann-La Roche Ag | Antiviral compounds |
| WO2012175581A1 (en) | 2011-06-24 | 2012-12-27 | F. Hoffmann-La Roche Ag | Antiviral compounds |
| PL2709613T5 (pl) | 2011-09-16 | 2020-12-14 | Gilead Pharmasset Llc | Metody leczenia hcv |
| CA2847083A1 (en) | 2011-10-10 | 2013-04-18 | 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 |
| JP5923181B2 (ja) | 2011-12-16 | 2016-05-24 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | Ｈｃｖｎｓ５ａの阻害剤 |
| HK1200835A1 (en) | 2011-12-20 | 2015-08-14 | Riboscience Llc | 4'-azido, 3'-fluoro substituted nucleoside derivatives as inhibitors of hcv rna replication |
| MY171577A (en) | 2011-12-20 | 2019-10-21 | Hoffmann La Roche | 2',4'-difluoro-2'-methyl substituted nucleoside derivatives as inhibitors of hcv rna replication |
| EP2817291A1 (en) | 2012-02-24 | 2014-12-31 | F. Hoffmann-La Roche AG | Antiviral compounds |
| US20140010783A1 (en) | 2012-07-06 | 2014-01-09 | Hoffmann-La Roche Inc. | Antiviral compounds |
| KR20150109451A (ko) | 2013-01-23 | 2015-10-01 | 에프. 호프만-라 로슈 아게 | 항바이러스성 트라이아졸 유도체 |
| PT2950786T (pt) | 2013-01-31 | 2020-03-03 | Gilead Pharmasset Llc | Formulação de combinação de dois compostos antivirais |
| CA2900319A1 (en) | 2013-03-05 | 2014-09-12 | F. Hoffmann-La Roche Ag | Antiviral compounds |
| EP2996695B1 (en) | 2013-05-16 | 2022-04-13 | Riboscience LLC | 4'-fluoro-2'-methyl substituted nucleoside derivatives |
| US20180200280A1 (en) | 2013-05-16 | 2018-07-19 | Riboscience Llc | 4'-Fluoro-2'-Methyl Substituted Nucleoside Derivatives as Inhibitors of HCV RNA Replication |
| AU2014272055A1 (en) | 2013-05-16 | 2015-12-24 | Riboscience Llc | 4'-azido, 3'-deoxy-3'-fluoro substituted nucleoside derivatives |
| EA201690473A1 (ru) | 2013-08-27 | 2017-03-31 | ГАЙЛИД ФАРМАССЕТ ЭлЭлСи | Комбинированный состав двух противовирусных соединений |
| CN105916500A (zh) | 2013-11-27 | 2016-08-31 | 欧洲筛选有限公司 | 用于治疗炎性疾病的化合物、药物组合物和方法 |
| EP3684374B1 (en) | 2017-09-21 | 2025-07-30 | Riboscience LLC | 4'-fluoro-2'-methyl substituted nucleoside derivatives as inhibitors of hcv rna replication |
| CN109678814B (zh) * | 2018-12-28 | 2021-03-23 | 浙江外国语学院 | 一种制备2-氯-1, 3-噻唑-5-甲醛的方法 |
| IL298760A (en) | 2020-06-05 | 2023-02-01 | Kinnate Biopharma Inc | Fibroblast growth factor receptor kinase inhibitors |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| AT395007B (de) * | 1990-03-29 | 1992-08-25 | Noe Christian | Modifizierte cyclische aminosaeuren und aus diesen synthetisierte dipeptide und verfahren zu ihrer herstellung |
| WO1993018765A1 (en) * | 1992-03-20 | 1993-09-30 | The Wellcome Foundation Limited | Indole derivatives with antiviral activity |
| EP1315698A1 (en) | 1998-04-23 | 2003-06-04 | Abbott Laboratories | Pyrrolidines as inhibitors of neuraminidases |
| US6455571B1 (en) | 1998-04-23 | 2002-09-24 | Abbott Laboratories | Inhibitors of neuraminidases |
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- 2002-10-30 ES ES02783059T patent/ES2289161T3/es not_active Expired - Lifetime
- 2002-10-30 AT AT02783059T patent/ATE370137T1/de not_active IP Right Cessation
- 2002-10-30 US US10/494,127 patent/US7259163B2/en not_active Expired - Fee Related
- 2002-10-30 EP EP02783059A patent/EP1440069B1/en not_active Expired - Lifetime
- 2002-10-30 JP JP2003540176A patent/JP2005515172A/ja not_active Ceased
- 2002-10-30 DE DE60221875T patent/DE60221875T2/de not_active Expired - Lifetime
- 2002-10-30 WO PCT/EP2002/012176 patent/WO2003037895A1/en not_active Ceased
- 2002-10-31 AR ARP020104160A patent/AR037182A1/es unknown
- 2002-10-31 TW TW091132224A patent/TW200302823A/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003037895A1 (en) | 2003-05-08 |
| US7259163B2 (en) | 2007-08-21 |
| DE60221875T2 (de) | 2007-12-20 |
| EP1440069B1 (en) | 2007-08-15 |
| TW200302823A (en) | 2003-08-16 |
| JP2005515172A (ja) | 2005-05-26 |
| US20050043390A1 (en) | 2005-02-24 |
| EP1440069A1 (en) | 2004-07-28 |
| AR037182A1 (es) | 2004-10-27 |
| ATE370137T1 (de) | 2007-09-15 |
| DE60221875D1 (de) | 2007-09-27 |
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