CN104163816A - Hcv ns5a的抑制剂 - Google Patents
Hcv ns5a的抑制剂 Download PDFInfo
- Publication number
- CN104163816A CN104163816A CN201410221684.8A CN201410221684A CN104163816A CN 104163816 A CN104163816 A CN 104163816A CN 201410221684 A CN201410221684 A CN 201410221684A CN 104163816 A CN104163816 A CN 104163816A
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- Prior art keywords
- compound
- independently
- alkyl
- suc
- heteroaryl
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title description 21
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- -1 heterocyclic radical Chemical class 0.000 claims description 178
- 125000001072 heteroaryl group Chemical group 0.000 claims description 173
- 125000003118 aryl group Chemical group 0.000 claims description 154
- 125000000217 alkyl group Chemical group 0.000 claims description 148
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- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 150000003527 tetrahydropyrans Chemical class 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229940021747 therapeutic vaccine Drugs 0.000 description 1
- 150000004867 thiadiazoles Chemical class 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 description 1
- 229960004231 thymalfasin Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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- 230000035897 transcription Effects 0.000 description 1
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- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- PRXNKYBFWAWBNZ-UHFFFAOYSA-N trimethylphenylammonium tribromide Chemical compound Br[Br-]Br.C[N+](C)(C)C1=CC=CC=C1 PRXNKYBFWAWBNZ-UHFFFAOYSA-N 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- 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
- 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
-
- 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
- C07D403/14—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 three or more hetero rings
-
- 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
- C07D405/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
-
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11972308P | 2008-12-03 | 2008-12-03 | |
| US61/119,723 | 2008-12-03 | ||
| US21488109P | 2009-04-28 | 2009-04-28 | |
| US17359009P | 2009-04-28 | 2009-04-28 | |
| US61/173,590 | 2009-04-28 | ||
| US61/214,881 | 2009-04-28 | ||
| US18295209P | 2009-06-01 | 2009-06-01 | |
| US18295809P | 2009-06-01 | 2009-06-01 | |
| US61/182,958 | 2009-06-01 | ||
| US61/182,952 | 2009-06-01 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200980154543.6A Division CN102647909B (zh) | 2008-12-03 | 2009-12-02 | Hcv ns5a的抑制剂 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104163816A true CN104163816A (zh) | 2014-11-26 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410221684.8A Pending CN104163816A (zh) | 2008-12-03 | 2009-12-02 | Hcv ns5a的抑制剂 |
| CN200980154543.6A Active CN102647909B (zh) | 2008-12-03 | 2009-12-02 | Hcv ns5a的抑制剂 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200980154543.6A Active CN102647909B (zh) | 2008-12-03 | 2009-12-02 | Hcv ns5a的抑制剂 |
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| EP (2) | EP2682393A1 (enExample) |
| JP (1) | JP5762971B2 (enExample) |
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| BR (1) | BRPI0922366B8 (enExample) |
| CA (1) | CA2746004C (enExample) |
| CL (1) | CL2011001333A1 (enExample) |
| CO (1) | CO6390077A2 (enExample) |
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| EA (1) | EA024853B1 (enExample) |
| ES (1) | ES2437156T3 (enExample) |
| HK (1) | HK1203929A1 (enExample) |
| HR (1) | HRP20130944T1 (enExample) |
| IL (2) | IL213277A (enExample) |
| MX (1) | MX2011005898A (enExample) |
| PE (2) | PE20120124A1 (enExample) |
| PL (1) | PL2373172T3 (enExample) |
| PT (1) | PT2373172E (enExample) |
| SG (1) | SG171889A1 (enExample) |
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| TW (2) | TWI573796B (enExample) |
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| HK1203929A1 (en) | 2008-12-03 | 2015-11-06 | 普雷西迪奥制药公司 | Inhibitors of hcv ns5a |
| JP2012510523A (ja) * | 2008-12-03 | 2012-05-10 | プレシディオ ファーマシューティカルズ インコーポレイテッド | Ｈｃｖｎｓ５ａの阻害剤 |
| SG172353A1 (en) | 2008-12-23 | 2011-07-28 | Abbott Lab | Anti-viral compounds |
| MX2011006332A (es) | 2008-12-23 | 2011-06-27 | Abbott Lab | Compuestos antivirales. |
| US8314135B2 (en) | 2009-02-09 | 2012-11-20 | Enanta Pharmaceuticals, Inc. | Linked dibenzimidazole antivirals |
| US8188132B2 (en) | 2009-02-17 | 2012-05-29 | Enanta Pharmaceuticals, Inc. | Linked dibenzimidazole derivatives |
| US8637561B2 (en) | 2009-02-17 | 2014-01-28 | Enanta Pharmaceuticals, Inc. | Linked diimidazole derivatives |
| US8242156B2 (en) | 2009-02-17 | 2012-08-14 | Enanta Pharmaceuticals, Inc. | Linked dibenzimidazole derivatives |
| US8394968B2 (en) | 2009-02-17 | 2013-03-12 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| TWI438200B (zh) | 2009-02-17 | 2014-05-21 | 必治妥美雅史谷比公司 | Ｃ型肝炎病毒抑制劑 |
| US8420686B2 (en) | 2009-02-17 | 2013-04-16 | Enanta Pharmaceuticals, Inc. | Linked diimidazole antivirals |
| RU2544010C2 (ru) * | 2009-02-27 | 2015-03-10 | Энанта Фармасьютикалс, Инк. | Ингибиторы вируса гепатита с |
| US9765087B2 (en) | 2009-02-27 | 2017-09-19 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
| US8101643B2 (en) | 2009-02-27 | 2012-01-24 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
| US8426458B2 (en) | 2009-02-27 | 2013-04-23 | Enanta Pharmaceuticals, Inc. | Hepatitis C Virus inhibitors |
| AU2013204195B2 (en) * | 2009-02-27 | 2016-09-22 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8673954B2 (en) | 2009-02-27 | 2014-03-18 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
| US8507522B2 (en) | 2009-03-06 | 2013-08-13 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| PL2410844T3 (pl) | 2009-03-27 | 2016-08-31 | Merck Sharp & Dohme | Inhibitory replikacji wirusa zapalenia wątroby typu c |
| US20190127365A1 (en) | 2017-11-01 | 2019-05-02 | Merck Sharp & Dohme Corp. | Inhibitors of hepatitis c virus replication |
| CA2756255A1 (en) | 2009-03-27 | 2010-09-30 | Presidio Pharmaceuticals, Inc. | Substituted bicyclic hcv inhibitors |
| US8796466B2 (en) | 2009-03-30 | 2014-08-05 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| TW201038559A (en) | 2009-04-09 | 2010-11-01 | Bristol Myers Squibb Co | Hepatitis C virus inhibitors |
| US8143414B2 (en) | 2009-04-13 | 2012-03-27 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CN102459165B (zh) | 2009-04-15 | 2015-09-02 | Abbvie公司 | 抗病毒化合物 |
| HUE036906T2 (hu) | 2009-05-13 | 2018-08-28 | Antivirális vegyületek | |
| US8138215B2 (en) | 2009-05-29 | 2012-03-20 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8211928B2 (en) | 2009-05-29 | 2012-07-03 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CA2737601C (en) | 2009-06-11 | 2014-10-21 | Abbott Laboratories | Anti-viral compounds |
| US8937150B2 (en) | 2009-06-11 | 2015-01-20 | Abbvie Inc. | Anti-viral compounds |
| AU2012203474B2 (en) * | 2009-06-11 | 2014-09-18 | Abbvie Ireland Unlimited Company | Anti-Viral Compounds |
| 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 |
| US8221737B2 (en) | 2009-06-16 | 2012-07-17 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8609648B2 (en) | 2009-07-02 | 2013-12-17 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| WO2011004276A1 (en) * | 2009-07-06 | 2011-01-13 | Pfizer Limited | Hepatitis c virus inhibitors |
| IN2012DN00999A (enExample) | 2009-07-16 | 2015-04-10 | Vertex Pharma | |
| MX2012002759A (es) | 2009-09-04 | 2012-04-30 | Glaxosmithkline Llc | Compuestos quimicos. |
| US8759332B2 (en) | 2009-09-11 | 2014-06-24 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8815928B2 (en) | 2009-09-11 | 2014-08-26 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8927709B2 (en) | 2009-09-11 | 2015-01-06 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8703938B2 (en) | 2009-09-11 | 2014-04-22 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8822700B2 (en) | 2009-09-11 | 2014-09-02 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| EP2475256A4 (en) | 2009-09-11 | 2013-06-05 | Enanta Pharm Inc | HEPATITIS C-VIRUS HEMMER |
| UA108211C2 (uk) * | 2009-11-04 | 2015-04-10 | Янссен Рід Айрленд | Бензімідазолімідазольні похідні |
| US20110274648A1 (en) | 2009-11-11 | 2011-11-10 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US20110269956A1 (en) | 2009-11-11 | 2011-11-03 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US20110281910A1 (en) | 2009-11-12 | 2011-11-17 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US8653070B2 (en) | 2009-12-14 | 2014-02-18 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8377980B2 (en) | 2009-12-16 | 2013-02-19 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2011075607A1 (en) * | 2009-12-18 | 2011-06-23 | Intermune, Inc. | Novel inhibitors of hepatitis c virus replication |
| US8362068B2 (en) * | 2009-12-18 | 2013-01-29 | Idenix Pharmaceuticals, Inc. | 5,5-fused arylene or heteroarylene hepatitis C virus inhibitors |
| US20130156731A1 (en) * | 2009-12-22 | 2013-06-20 | Kevin X. Chen | Fused tricyclic compounds and methods of use thereof for the treatment of viral diseas |
| US8362020B2 (en) | 2009-12-30 | 2013-01-29 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CN102843909A (zh) | 2010-01-25 | 2012-12-26 | 埃南塔制药公司 | 丙型肝炎病毒抑制剂 |
| US8933110B2 (en) | 2010-01-25 | 2015-01-13 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| DK2536285T3 (en) | 2010-02-18 | 2018-07-16 | Vtv Therapeutics Llc | Substituted fused imidazole derivatives, pharmaceutical compositions and methods for their use |
| US8759535B2 (en) | 2010-02-18 | 2014-06-24 | High Point Pharmaceuticals, Llc | Substituted fused imidazole derivatives, pharmaceutical compositions, and methods of use thereof |
| 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 |
| CN102858157A (zh) * | 2010-03-04 | 2013-01-02 | 埃南塔制药公司 | 作为hcv复制的抑制剂的组合药物活性剂 |
| AR080676A1 (es) | 2010-03-09 | 2012-05-02 | Schering Corp | Compuestos de sililo triciclicos fusionados y metodos de uso de los mismos para el tratamiento de enfermedades virales |
| CA2794145A1 (en) | 2010-03-24 | 2011-09-29 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
| WO2011127350A1 (en) | 2010-04-09 | 2011-10-13 | Enanta Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
| EP2575866A4 (en) * | 2010-05-24 | 2013-10-16 | Presidio Pharmaceuticals Inc | HCV NS5A INHIBITORS |
| 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 |
| HUE029174T2 (hu) | 2010-06-24 | 2017-02-28 | Gilead Sciences Inc | Pirazolo[1,5-A]pirimidinek és -triazinok mint antivirális szerek |
| JP2013531011A (ja) | 2010-06-28 | 2013-08-01 | 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 |
| CA2803248A1 (en) | 2010-06-28 | 2012-01-12 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of flavivirus infections |
| CA2805440A1 (en) | 2010-07-26 | 2012-02-09 | Merck Sharp & Dohme Corp. | Substituted biphenylene compounds and methods of use thereof for the treatment of viral diseases |
| US8815849B2 (en) * | 2010-07-26 | 2014-08-26 | Janssen R&D Ireland | Hetero-bicyclic derivatives as HCV inhibitors |
| US20120195857A1 (en) * | 2010-08-12 | 2012-08-02 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| WO2012021704A1 (en) * | 2010-08-12 | 2012-02-16 | Enanta Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
| WO2012024363A2 (en) | 2010-08-17 | 2012-02-23 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of flaviviridae viral infections |
| WO2012041014A1 (en) * | 2010-09-29 | 2012-04-05 | Merck Sharp & Dohme Corp. | Tetracyclic indole derivatives for treating hepatitis c virus infection |
| CN103459399A (zh) * | 2010-09-29 | 2013-12-18 | 默沙东公司 | 用于治疗丙型肝炎病毒感染的四环吲哚衍生物 |
| JP2013540122A (ja) | 2010-09-29 | 2013-10-31 | メルク・シャープ・エンド・ドーム・コーポレイション | 縮合四環式化合物誘導体およびウィルス疾患治療のためのそれの使用方法 |
| WO2012050918A2 (en) | 2010-09-29 | 2012-04-19 | Presidio Pharmaceutical, Inc. | Tricyclic fused ring inhibitors of hepatitis c |
| AU2014203655B2 (en) * | 2010-10-13 | 2016-07-07 | Abbvie Ireland Unlimited Company | Anti-viral compounds |
| US8552047B2 (en) | 2011-02-07 | 2013-10-08 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2012122716A1 (en) | 2011-03-17 | 2012-09-20 | Merck Sharp & Dohme Corp. | Tetracyclic xanthene derivatives and methods of use thereof for treatment of viral diseases |
| US9546160B2 (en) | 2011-05-12 | 2017-01-17 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US10201584B1 (en) | 2011-05-17 | 2019-02-12 | Abbvie Inc. | Compositions and methods for treating HCV |
| WO2012158861A2 (en) | 2011-05-18 | 2012-11-22 | Enanta Pharmaceuticals, Inc. | Processes for the preparation of 5-azaspiro[2.4]heptane-6-carboxylic acid and its derivatives |
| US8975276B2 (en) | 2011-06-29 | 2015-03-10 | Bristol-Myers Squibb Company | Inhibitors of PDE10 |
| US9303061B2 (en) | 2011-07-09 | 2016-04-05 | Sunshine Luke Pharma Co., Ltd. | Spiro compounds as Hepatitis C virus inhibitors |
| EP2733141B1 (en) * | 2011-07-15 | 2019-01-09 | Shionogi & Co., Ltd. | Azabenzimidazole derivative having ampk-activating activity |
| 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 |
| WO2013039876A1 (en) | 2011-09-14 | 2013-03-21 | Merck Sharp & Dohme Corp. | Silyl-containing heterocyclic compounds and methods of use thereof for the treatment of viral diseases |
| SMT201800087T1 (it) | 2011-09-16 | 2018-03-08 | Gilead Pharmasset Llc | Metodi per trattare hcv |
| MX2014006745A (es) * | 2011-12-16 | 2014-10-15 | Hoffmann La Roche | Inhibidores de hcv ns5a. |
| EP2794611B1 (en) | 2011-12-22 | 2017-10-11 | Gilead Sciences, Inc. | Pyrazolo[1,5-a]pyrimidines as antiviral agents |
| WO2013098313A1 (en) | 2011-12-28 | 2013-07-04 | Janssen R&D Ireland | Hetero-bicyclic derivatives as hcv inhibitors |
| BR112014016007A8 (pt) * | 2011-12-28 | 2017-07-04 | Janssen R&D Ireland | derivados de quinazolinona como inibidores de vhc |
| US9034832B2 (en) | 2011-12-29 | 2015-05-19 | Abbvie Inc. | Solid compositions |
| US9326973B2 (en) | 2012-01-13 | 2016-05-03 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| MX2014009693A (es) * | 2012-02-13 | 2014-09-08 | Presidio Pharmaceuticals Inc | Formas solidas que comprenden inhibidores de ns5a de hcv, sus composiciones y sus usos. |
| JP6129217B2 (ja) | 2012-03-09 | 2017-05-17 | フィブロジェン インコーポレイテッド | Ｈｉｆヒドロキシラーゼインヒビターとしての４−ヒドロキシ−イソキノリン化合物 |
| EP2827876A4 (en) | 2012-03-22 | 2015-10-28 | Alios Biopharma Inc | PHARMACEUTICAL COMBINATIONS WITH A THIONUCLEOTIDE ANALOG |
| EP2838900B1 (en) | 2012-04-17 | 2019-08-21 | Gilead Sciences, Inc. | Compounds and methods for antiviral treatment |
| JP6006008B2 (ja) * | 2012-06-14 | 2016-10-12 | ユー・ディー・シー アイルランド リミテッド | 化合物、有機電界発光素子並びに該有機電界発光素子を用いた発光装置、表示装置及び照明装置 |
| TWI610916B (zh) * | 2012-08-03 | 2018-01-11 | 廣東東陽光藥業有限公司 | 作爲丙型肝炎抑制劑的橋環化合物及其在藥物中的應用 |
| CN102796084A (zh) * | 2012-09-10 | 2012-11-28 | 合肥科尚医药科技有限公司 | 一种活性物质及其在治疗丙型肝炎中的应用及制备方法 |
| WO2014055069A1 (en) * | 2012-10-02 | 2014-04-10 | Presidio Pharmaceuticals, Inc. | Solid forms comprising an inhibitor of hcv ns5a, compositions thereof, and uses therewith |
| WO2014082380A1 (en) | 2012-11-29 | 2014-06-05 | Sunshine Lake Pharma Co., Ltd. | Fused ring compounds as hepatitis c virus inhibitors, pharmaceutical compositions and uses thereof |
| WO2014082379A1 (en) | 2012-11-29 | 2014-06-05 | Sunshine Lake Pharma Co.,Ltd. | Spiro ring compound as hepatitis c virus (hcv) inhibitor and uses thereof field of the invention |
| JP6353460B2 (ja) * | 2012-12-06 | 2018-07-04 | バルーク エス．ブランバーグ インスティチュート | Ｈｂｖ感染に対する抗ウイルス剤としての官能化ベンズアミド誘導体 |
| WO2014110687A1 (en) | 2013-01-16 | 2014-07-24 | Merck Sharp & Dohme Corp. | Thiazolyl-substitued tetracyclic compounds and methods of use thereof for treatment of viral diseases |
| EA029081B9 (ru) | 2013-01-31 | 2018-09-28 | Джилид Фармассет Ллс | Комбинированный состав двух противовирусных соединений |
| US20150065439A1 (en) | 2013-02-28 | 2015-03-05 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions |
| US11484534B2 (en) | 2013-03-14 | 2022-11-01 | Abbvie Inc. | Methods for treating HCV |
| US9717712B2 (en) | 2013-07-02 | 2017-08-01 | Bristol-Myers Squibb Company | Combinations comprising tricyclohexadecahexaene derivatives for use in the treatment of hepatitis C virus |
| US20150023913A1 (en) | 2013-07-02 | 2015-01-22 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| EP3021845A1 (en) | 2013-07-17 | 2016-05-25 | Bristol-Myers Squibb Company | Combinations comprising biphenyl derivatives for use in the treatment of hcv |
| PL3038601T3 (pl) | 2013-08-27 | 2020-08-24 | Gilead Pharmasset Llc | Formulacja złożona dwóch związków przeciwwirusowych |
| WO2015065817A1 (en) | 2013-10-30 | 2015-05-07 | Merck Sharp & Dohme Corp. | Pseudopolymorphs of an hcv ns5a inhibitor and uses thereof |
| WO2015089810A1 (en) | 2013-12-20 | 2015-06-25 | Merck Sharp & Dohme Corp. | Fused tetracyclic heterocyclic compounds and methods of use thereof for the treatment of viral diseases |
| WO2015103490A1 (en) | 2014-01-03 | 2015-07-09 | Abbvie, Inc. | Solid antiviral dosage forms |
| CN104803989B (zh) | 2014-01-23 | 2017-12-22 | 广东东阳光药业有限公司 | 作为丙型肝炎抑制剂的桥环化合物及其在药物中的应用 |
| CN107954997A (zh) * | 2014-02-21 | 2018-04-24 | 常州寅盛药业有限公司 | 作为丙肝病毒抑制剂的联环化合物 |
| TWI721947B (zh) | 2014-06-11 | 2021-03-21 | 美商基利法瑪席特有限責任公司 | 抗病毒化合物的固態形式 |
| WO2016089648A1 (en) | 2014-12-01 | 2016-06-09 | Vtv Therapeutics Llc | Bach 1 inhibitors in combination with nrf2 activators and pharmaceutical compositions thereof |
| GB201506660D0 (en) | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| GB201506658D0 (en) | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| WO2017019828A1 (en) * | 2015-07-30 | 2017-02-02 | Bristol-Myers Squibb Company | Aryl substituted bicyclic heteroaryl compounds |
| US10617675B2 (en) | 2015-08-06 | 2020-04-14 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CN107663196A (zh) * | 2016-07-27 | 2018-02-06 | 广东东阳光药业有限公司 | 制备化合物的方法 |
| WO2018032467A1 (en) | 2016-08-18 | 2018-02-22 | Merck Sharp & Dohme Corp. | Chromane-substitued tetracyclic compounds and uses thereof for treatment of viral diseases |
| CN113167802B (zh) | 2018-12-04 | 2025-02-07 | 百时美施贵宝公司 | 通过多同位素体反应监测使用样品内校准曲线的分析方法 |
| JP7269584B2 (ja) * | 2019-04-08 | 2023-05-09 | 国立大学法人千葉大学 | キノリン化合物の製造方法 |
| CN110498759A (zh) * | 2019-09-12 | 2019-11-26 | 天津瑞岭化工有限公司 | 异吲哚啉酮类化合物的合成方法 |
| WO2022078407A1 (en) * | 2020-10-13 | 2022-04-21 | Gasherbrum Bio, Inc. | Heterocyclic glp-1 agonists |
| AU2022277904B2 (en) | 2021-05-21 | 2025-06-12 | Gilead Sciences, Inc. | Tetracyclic compounds for the treatment of zika virus infection |
| KR20240012476A (ko) | 2021-05-21 | 2024-01-29 | 길리애드 사이언시즈, 인코포레이티드 | 지카 바이러스 저해제로서의 펜타사이클릭 유도체 |
| AU2022370483A1 (en) * | 2021-10-20 | 2024-05-02 | Assembly Biosciences, Inc. | Novel crystalline forms |
| CN114262263B (zh) * | 2021-12-28 | 2024-04-19 | 河北美星化工有限公司 | 一种4-碘苯酚的制备方法 |
Family Cites Families (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2526230A1 (de) * | 1975-06-12 | 1976-12-16 | Hoechst Ag | Neue benzoxazol-derivate, verfahren zu ihrer herstellung und ihre anwendung als optische aufheller |
| CA2034309C (en) * | 1990-01-22 | 1997-04-01 | Takashi Iwaki | Mesomorphic compound, liquid crystal composition containing same, liquid crystal device using same and display apparatus |
| AU702487B2 (en) | 1995-08-30 | 1999-02-25 | G.D. Searle & Co. | Meta-guanidine, urea, thiourea or azacyclic amino benzoic acid derivatives as integrin antagonists |
| US5807876A (en) | 1996-04-23 | 1998-09-15 | Vertex Pharmaceuticals Incorporated | Inhibitors of IMPDH enzyme |
| US6054472A (en) | 1996-04-23 | 2000-04-25 | Vertex Pharmaceuticals, Incorporated | Inhibitors of IMPDH enzyme |
| WO1997040028A1 (en) | 1996-04-23 | 1997-10-30 | Vertex Pharmaceuticals Incorporated | Urea derivatives as inhibitors of impdh enzyme |
| HU227742B1 (en) | 1996-10-18 | 2012-02-28 | Vertex Pharma | Inhibitors of serine proteases, particularly hepatitis c virus ns3 protease |
| GB9623908D0 (en) | 1996-11-18 | 1997-01-08 | Hoffmann La Roche | Amino acid derivatives |
| CA2282398A1 (en) | 1997-03-14 | 1998-09-17 | Steven M. Ronkin | Inhibitors of impdh enzyme |
| US6010848A (en) | 1997-07-02 | 2000-01-04 | Smithkline Beecham Corporation | Screening methods using an atpase protein from hepatitis C virus |
| NZ503263A (en) | 1997-08-11 | 2002-10-25 | Boehringer Ingelheim Ca Ltd | Hepatitis C NS3 protease inhibitor peptides and peptide analogues |
| WO1999037304A1 (en) | 1998-01-27 | 1999-07-29 | Aventis Pharmaceuticals Products Inc. | SUBSTITUTED OXOAZAHETEROCYCLYL FACTOR Xa INHIBITORS |
| WO2000006529A1 (en) | 1998-07-27 | 2000-02-10 | Istituto Di Ricerche Di Biologia Molecolare P Angeletti S.P.A. | Diketoacid-derivatives as inhibitors of polymerases |
| US6323180B1 (en) | 1998-08-10 | 2001-11-27 | Boehringer Ingelheim (Canada) Ltd | Hepatitis C inhibitor tri-peptides |
| ID27787A (id) | 1998-08-21 | 2001-04-26 | Viro Pharma Inc | Senyawa, komposisi dan metode untuk pengobatan atau pencegahan infeksi yang disebabkan oleh virus dan penyakit-penyakit yang berkaitan |
| EP1109580A4 (en) | 1998-09-04 | 2004-05-26 | Viropharma Inc | METHOD FOR TREATING OR PREVENTING VIRAL INFECTIONS AND RELATED DISEASES |
| CA2345347A1 (en) | 1998-09-25 | 2000-04-06 | Viropharma Incorporated | Methods for treating or preventing viral infections and associated diseases |
| WO2000056331A1 (en) | 1999-03-19 | 2000-09-28 | Vertex Pharmaceuticals Incorporated | Inhibitors of impdh enzyme |
| EP1225899A2 (en) | 1999-11-04 | 2002-07-31 | Virochem Pharma Inc. | Method for the treatment or prevention of flaviviridae viral infection using nucleoside analogues |
| JP2004509066A (ja) | 2000-05-10 | 2004-03-25 | スミスクライン・ビーチャム・コーポレイション | 新規抗感染症薬 |
| US6448281B1 (en) | 2000-07-06 | 2002-09-10 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
| SV2003000617A (es) | 2000-08-31 | 2003-01-13 | Lilly Co Eli | Inhibidores de la proteasa peptidomimetica ref. x-14912m |
| EP1256628A3 (en) | 2001-05-10 | 2003-03-19 | Agouron Pharmaceuticals, Inc. | Hepatitis c virus (hcv) ns5b rna polymerase and mutants thereof |
| WO2002100846A1 (en) | 2001-06-11 | 2002-12-19 | Shire Biochem Inc. | Compounds and methods for the treatment or prevention of flavivirus infections |
| BR0210357A (pt) | 2001-06-11 | 2004-06-29 | Shire Biochem Inc | Composto e métodos para o tratamento ou a prevenção de infecções pelo flavivìrus |
| 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 |
| WO2003037894A1 (en) | 2001-11-02 | 2003-05-08 | Glaxo Group Limited | 4-(5-membered)-heteroaryl acyl pyrrolidine derivatives as hcv inhibitors |
| EP1440068A1 (en) | 2001-11-02 | 2004-07-28 | Glaxo Group Limited | Acyl dihydro pyrrole derivatives as hcv inhibitors |
| ATE370137T1 (de) | 2001-11-02 | 2007-09-15 | Glaxo Group Ltd | 4-(6-gliedriger)-heteroaryl-acyl-pyrrolidin derivate als hcv-inhibitoren |
| AR039555A1 (es) | 2001-11-08 | 2005-02-23 | Upjohn Co | Derivados n,n'-sustituidos de 1,3-diamino-2-hidroxipropano |
| US7189724B2 (en) * | 2003-04-15 | 2007-03-13 | Valeant Research And Development | Quinoxaline derivatives having antiviral activity |
| NL1026826C2 (nl) | 2003-08-13 | 2007-01-04 | Pharmacia Corp | Gesubstitueerde pyridinonen. |
| US20050131042A1 (en) | 2003-12-11 | 2005-06-16 | Flentge Charles A. | HIV protease inhibiting compounds |
| US20050131017A1 (en) | 2003-12-11 | 2005-06-16 | Degoey David A. | HIV protease inhibiting compounds |
| US7834043B2 (en) | 2003-12-11 | 2010-11-16 | Abbott Laboratories | HIV protease inhibiting compounds |
| EP1713822B1 (en) | 2004-01-30 | 2010-03-17 | Medivir AB | Hcv ns-3 serine protease inhibitors |
| AR047894A1 (es) | 2004-02-25 | 2006-03-01 | Wyeth Corp | Derivados de tiofeno como inhibidores de la proteina tirosina fosfatasa 1b (ptpasa 1b); metodos para su preparacion, composiciones farmaceuticas que los contienen y su uso en el tratamiento de enfermedades mediadas por ptpasa 1b |
| WO2005097765A1 (en) | 2004-03-31 | 2005-10-20 | Exelixis, Inc. | Anaplastic lymphoma kinase modulators and methods of use |
| RU2007130896A (ru) * | 2005-01-14 | 2009-02-20 | Дженелэбс Текнолоджиз, Инк. (Us) | Индольные производные для лечения вирусных инфекций |
| US7473784B2 (en) * | 2005-08-01 | 2009-01-06 | Bristol-Myers Squibb Company | Benzothiazole and azabenzothiazole compounds useful as kinase inhibitors |
| JP2010500372A (ja) | 2006-08-09 | 2010-01-07 | スミスクライン ビーチャム コーポレーション | オピオイド受容体に対するアンタゴニストまたはインバースアゴニストとしての新規化合物 |
| US7659270B2 (en) * | 2006-08-11 | 2010-02-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8329159B2 (en) * | 2006-08-11 | 2012-12-11 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7759495B2 (en) * | 2006-08-11 | 2010-07-20 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| AU2007309427B2 (en) | 2006-10-23 | 2013-02-28 | Cephalon, Inc. | Fused bicyclic derivatives of 2,4-diaminopyrimidine as ALK and c-Met inhibitors |
| US7906655B2 (en) * | 2008-08-07 | 2011-03-15 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| JP2012510523A (ja) * | 2008-12-03 | 2012-05-10 | プレシディオ ファーマシューティカルズ インコーポレイテッド | Ｈｃｖｎｓ５ａの阻害剤 |
| HK1203929A1 (en) | 2008-12-03 | 2015-11-06 | 普雷西迪奥制药公司 | Inhibitors of hcv ns5a |
| EP2393359A4 (en) * | 2009-02-09 | 2012-10-03 | Enanta Pharm Inc | COMPOUND DIBENZIMIDAZOLE DERIVATIVES |
| WO2010096462A1 (en) * | 2009-02-17 | 2010-08-26 | Enanta Pharmaceuticals, Inc | Linked diimidazole derivatives |
| RU2544010C2 (ru) * | 2009-02-27 | 2015-03-10 | Энанта Фармасьютикалс, Инк. | Ингибиторы вируса гепатита с |
| US8101643B2 (en) | 2009-02-27 | 2012-01-24 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
| US8796466B2 (en) | 2009-03-30 | 2014-08-05 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| HUE036906T2 (hu) | 2009-05-13 | 2018-08-28 | Antivirális vegyületek | |
| WO2010148006A1 (en) * | 2009-06-16 | 2010-12-23 | Enanta Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
| EP2475256A4 (en) * | 2009-09-11 | 2013-06-05 | Enanta Pharm Inc | HEPATITIS C-VIRUS HEMMER |
| UA108211C2 (uk) | 2009-11-04 | 2015-04-10 | Янссен Рід Айрленд | Бензімідазолімідазольні похідні |
| US20110269956A1 (en) * | 2009-11-11 | 2011-11-03 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US20110274648A1 (en) | 2009-11-11 | 2011-11-10 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| WO2011075607A1 (en) | 2009-12-18 | 2011-06-23 | Intermune, Inc. | Novel inhibitors of hepatitis c virus replication |
| WO2011091446A1 (en) | 2010-01-22 | 2011-07-28 | Glaxosmithkline Llc | Chemical compounds |
-
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