MX2009001436A - Inhibidores del virus de la hepatitis c. - Google Patents
Inhibidores del virus de la hepatitis c.Info
- Publication number
- MX2009001436A MX2009001436A MX2009001436A MX2009001436A MX2009001436A MX 2009001436 A MX2009001436 A MX 2009001436A MX 2009001436 A MX2009001436 A MX 2009001436A MX 2009001436 A MX2009001436 A MX 2009001436A MX 2009001436 A MX2009001436 A MX 2009001436A
- Authority
- MX
- Mexico
- Prior art keywords
- imidazol
- pyrrolidinyl
- phenyl
- mmol
- oxo
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title claims description 6
- 241000711549 Hepacivirus C Species 0.000 title abstract description 46
- 150000001875 compounds Chemical class 0.000 claims abstract description 180
- 239000000203 mixture Substances 0.000 claims abstract description 174
- 150000003839 salts Chemical class 0.000 claims abstract description 60
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 37
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 12
- 208000015181 infectious disease Diseases 0.000 claims abstract description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 8
- -1 carboxy, formyl Chemical group 0.000 claims description 184
- 125000000217 alkyl group Chemical group 0.000 claims description 97
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 43
- 125000003118 aryl group Chemical group 0.000 claims description 42
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- 125000000623 heterocyclic group Chemical group 0.000 claims description 38
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 33
- 239000002253 acid Substances 0.000 claims description 32
- 229910052757 nitrogen Inorganic materials 0.000 claims description 32
- 125000003545 alkoxy group Chemical group 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 28
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 28
- 125000001188 haloalkyl group Chemical group 0.000 claims description 27
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 24
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- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 125000003342 alkenyl group Chemical group 0.000 claims description 18
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- 230000000694 effects Effects 0.000 claims description 16
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 16
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
- 229910003827 NRaRb Inorganic materials 0.000 claims description 12
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 12
- AOGFRXVTKLIGBI-UHFFFAOYSA-N 2-(dimethylamino)-2-phenylacetaldehyde Chemical compound CN(C)C(C=O)C1=CC=CC=C1 AOGFRXVTKLIGBI-UHFFFAOYSA-N 0.000 claims description 11
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- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 9
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- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 9
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- 101100244083 Arabidopsis thaliana PKL gene Proteins 0.000 claims description 8
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- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 5
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- 125000004449 heterocyclylalkenyl group Chemical group 0.000 claims description 5
- UBCHPRBFMUDMNC-UHFFFAOYSA-N 1-(1-adamantyl)ethanamine Chemical compound C1C(C2)CC3CC2CC1(C(N)C)C3 UBCHPRBFMUDMNC-UHFFFAOYSA-N 0.000 claims description 4
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- 125000001475 halogen functional group Chemical group 0.000 claims 9
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 4
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- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- KWMKJWWQIZDEMA-JWBZKWLISA-N (2r)-2-(diethylamino)-2-phenyl-1-[(2s)-2-[5-[4-[5-[2-[(2s)-pyrrolidin-2-yl]-1h-imidazol-5-yl]pyrimidin-2-yl]phenyl]-1h-imidazol-2-yl]pyrrolidin-1-yl]ethanone Chemical compound N1C([C@@H]2CCCN2C(=O)[C@H](N(CC)CC)C=2C=CC=CC=2)=NC=C1C(C=C1)=CC=C1C(N=C1)=NC=C1C(N1)=CN=C1[C@@H]1CCCN1 KWMKJWWQIZDEMA-JWBZKWLISA-N 0.000 claims 1
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- 229960005055 sodium ascorbate Drugs 0.000 description 1
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- 239000012312 sodium hydride Substances 0.000 description 1
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- MIXCUJKCXRNYFM-UHFFFAOYSA-M sodium;diiodomethanesulfonate;n-propyl-n-[2-(2,4,6-trichlorophenoxy)ethyl]imidazole-1-carboxamide Chemical compound [Na+].[O-]S(=O)(=O)C(I)I.C1=CN=CN1C(=O)N(CCC)CCOC1=C(Cl)C=C(Cl)C=C1Cl MIXCUJKCXRNYFM-UHFFFAOYSA-M 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- JENNMRCJADUWJR-LLVKDONJSA-N tert-butyl (2r)-2-(methoxycarbonylamino)-2-phenylacetate Chemical compound COC(=O)N[C@@H](C(=O)OC(C)(C)C)C1=CC=CC=C1 JENNMRCJADUWJR-LLVKDONJSA-N 0.000 description 1
- HJLYKRGXTOVWFL-SNVBAGLBSA-N tert-butyl (2r)-2-amino-2-phenylacetate Chemical compound CC(C)(C)OC(=O)[C@H](N)C1=CC=CC=C1 HJLYKRGXTOVWFL-SNVBAGLBSA-N 0.000 description 1
- YDBPZCVWPFMBDH-QMMMGPOBSA-N tert-butyl (2s)-2-formylpyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C=O YDBPZCVWPFMBDH-QMMMGPOBSA-N 0.000 description 1
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- MYBNTSLQHDGJFY-UHFFFAOYSA-N tert-butyl 2-anilinoacetate Chemical compound CC(C)(C)OC(=O)CNC1=CC=CC=C1 MYBNTSLQHDGJFY-UHFFFAOYSA-N 0.000 description 1
- UIYOVVYZPVVUMJ-UHFFFAOYSA-N tert-butyl carbamoyl carbonate Chemical compound CC(C)(C)OC(=O)OC(N)=O UIYOVVYZPVVUMJ-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
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- 125000000335 thiazolyl group Chemical group 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 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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- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
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- 230000029812 viral genome replication Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
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- 238000005303 weighing Methods 0.000 description 1
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- 235000010493 xanthan gum Nutrition 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
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic 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
-
- 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
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61P31/20—Antivirals for DNA viruses
-
- 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Biotechnology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US83699906P | 2006-08-11 | 2006-08-11 | |
| PCT/US2007/075545 WO2008021928A2 (en) | 2006-08-11 | 2007-08-09 | Hepatitis c virus inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2009001436A true MX2009001436A (es) | 2009-02-17 |
Family
ID=38895921
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2009001436A MX2009001436A (es) | 2006-08-11 | 2007-08-09 | Inhibidores del virus de la hepatitis c. |
Country Status (16)
| Country | Link |
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Families Citing this family (166)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7745636B2 (en) | 2006-08-11 | 2010-06-29 | 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 |
| US8303944B2 (en) * | 2006-08-11 | 2012-11-06 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| EP2494991A1 (en) | 2007-05-04 | 2012-09-05 | Vertex Pharmaceuticals Incorporated | Combination therapy for the treatment of HCV infection |
| US7741347B2 (en) | 2007-05-17 | 2010-06-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CN103450077B (zh) | 2007-06-08 | 2016-07-06 | 满康德股份有限公司 | IRE-1α抑制剂 |
| BRPI0813999A2 (pt) * | 2007-07-05 | 2019-10-01 | Array Biopharma Inc | ciclopentanos de pirimidil como inibidores de akt proteína cinase |
| US7728027B2 (en) * | 2007-08-08 | 2010-06-01 | Bristol-Myers Squibb Company | Process for synthesizing compounds useful for treating hepatitis C |
| US8629171B2 (en) | 2007-08-08 | 2014-01-14 | Bristol-Myers Squibb Company | Crystalline form of methyl ((1S)-1-((25)-2-(5-(4'-(2-((25)-1((2S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-2-pyrrolidinyl)-1H-imidazol-2-yl)-1-pyrrolidinyl)carbonyl)-2-methylpropyl)carbamate dihydrochloride salt |
| CA2715400A1 (en) | 2008-02-12 | 2009-08-20 | Bristol-Myers Squibb Company | Heterocyclic derivatives as hepatitis c virus inhibitors |
| NZ587323A (en) * | 2008-02-12 | 2012-02-24 | Bristol Myers Squibb Co | Hepatitis c virus inhibitors |
| JP5312486B2 (ja) * | 2008-02-13 | 2013-10-09 | ブリストル−マイヤーズ スクイブ カンパニー | Ｃ型肝炎ウイルス阻害剤 |
| US7704992B2 (en) | 2008-02-13 | 2010-04-27 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8147818B2 (en) * | 2008-02-13 | 2012-04-03 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7906655B2 (en) | 2008-08-07 | 2011-03-15 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8536185B2 (en) | 2008-09-22 | 2013-09-17 | Cayman Chemical Company, Incorporated | Multiheteroaryl compounds as inhibitors of H-PGDS and their use for treating prostaglandin D2 mediated diseases |
| US8383094B2 (en) | 2008-10-01 | 2013-02-26 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2010062821A1 (en) * | 2008-11-28 | 2010-06-03 | Glaxosmithkline Llc | Anti-viral compounds, compositions, and methods of use |
| WO2010065681A1 (en) * | 2008-12-03 | 2010-06-10 | Presidio Pharmaceuticals, Inc. | Inhibitors of hcv ns5a |
| CN104163816A (zh) * | 2008-12-03 | 2014-11-26 | 普雷西迪奥制药公司 | Hcv ns5a的抑制剂 |
| MX2011006332A (es) | 2008-12-23 | 2011-06-27 | Abbott Lab | Compuestos antivirales. |
| 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 |
| US8420686B2 (en) | 2009-02-17 | 2013-04-16 | Enanta Pharmaceuticals, Inc. | Linked diimidazole 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 |
| CA2753313A1 (en) * | 2009-02-23 | 2010-08-26 | Presidio Pharmaceuticals, Inc. | Inhibitors of hcv ns5a |
| US8101643B2 (en) * | 2009-02-27 | 2012-01-24 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
| KR20130130875A (ko) * | 2009-02-27 | 2013-12-02 | 이난타 파마슈티칼스, 인코포레이티드 | Ｃ형 간염 바이러스 억제제 |
| US8426458B2 (en) | 2009-02-27 | 2013-04-23 | Enanta Pharmaceuticals, Inc. | Hepatitis C Virus inhibitors |
| US9765087B2 (en) | 2009-02-27 | 2017-09-19 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
| US8673954B2 (en) | 2009-02-27 | 2014-03-18 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
| US10752611B2 (en) | 2009-02-27 | 2020-08-25 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
| US8507522B2 (en) | 2009-03-06 | 2013-08-13 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| EP2408449A4 (en) | 2009-03-18 | 2012-08-08 | Univ Leland Stanford Junior | METHOD AND COMPOSITIONS FOR TREATING FLAVIVIRIDAE VIRUS INFECTIONS |
| KR20110131312A (ko) * | 2009-03-27 | 2011-12-06 | 프레시디오 파마슈티칼스, 인코포레이티드 | 융합된 고리 ｃ형 간염 억제제 |
| CA2756255A1 (en) | 2009-03-27 | 2010-09-30 | Presidio Pharmaceuticals, Inc. | Substituted bicyclic hcv inhibitors |
| TWI476190B (zh) * | 2009-03-30 | 2015-03-11 | 必治妥美雅史谷比公司 | Ｃ型肝炎病毒抑制劑 |
| 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 |
| EP2419404B1 (en) * | 2009-04-15 | 2015-11-04 | AbbVie Inc. | Anti-viral compounds |
| WO2010132538A1 (en) * | 2009-05-12 | 2010-11-18 | Schering Corporation | Fused tricyclic aryl compounds useful for the treatment of viral diseases |
| MX363732B (es) * | 2009-05-13 | 2019-04-01 | Gilead Pharmasset Llc Star | Compuestos antivirales. |
| CA2762885A1 (en) | 2009-05-29 | 2010-12-02 | Schering Corporation | Antiviral compounds composed of three aligned aryl moieties to treat diseases such as hepatitis c |
| EP2435424B1 (en) | 2009-05-29 | 2015-01-21 | Merck Sharp & Dohme Corp. | Antiviral compounds composed of three linked aryl moieties to treat diseases such as hepatitis c |
| 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 |
| 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 |
| DK2368890T3 (da) * | 2009-06-11 | 2013-07-22 | Abbvie Bahamas Ltd | Hepatitis C-virusinhibitorer |
| 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 |
| CN102656160A (zh) | 2009-07-16 | 2012-09-05 | 顶点制药公司 | 用于治疗或预防黄病毒感染的苯并咪唑类似物 |
| WO2011015658A1 (en) | 2009-08-07 | 2011-02-10 | Tibotec Pharmaceuticals | Bis-benzimidazole derivatives as hepatitis c virus inhibitors |
| RU2538507C2 (ru) | 2009-08-07 | 2015-01-10 | Тиботек Фармасьютикалз | Фенилэтинильные производные в качестве ингибиторов вируса гепатита с |
| CA2772484A1 (en) | 2009-09-03 | 2011-03-10 | Tibotec Pharmaceuticals | Bis-benzimidazole derivatives |
| PE20120993A1 (es) | 2009-09-04 | 2012-08-22 | Janssen Pharmaceuticals Inc | Derivados bifenilicos como antivirales |
| US8822700B2 (en) * | 2009-09-11 | 2014-09-02 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| WO2011031934A1 (en) * | 2009-09-11 | 2011-03-17 | Enanta Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
| US8815928B2 (en) | 2009-09-11 | 2014-08-26 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US9156818B2 (en) | 2009-09-11 | 2015-10-13 | 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 |
| US8759332B2 (en) * | 2009-09-11 | 2014-06-24 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| 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 |
| US20110281910A1 (en) | 2009-11-12 | 2011-11-17 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| CA2782024A1 (en) | 2009-11-25 | 2011-06-03 | Schering Corporation | Fused tricyclic compounds and derivatives thereof useful for the treatment of viral diseases |
| US20110137633A1 (en) * | 2009-12-03 | 2011-06-09 | Abbott Laboratories | Anti-viral compounds and methods of identifying the same |
| CN102482269B (zh) * | 2009-12-04 | 2015-07-29 | 财团法人卫生研究院 | 脯氨酸衍生物 |
| EP2512480A4 (en) * | 2009-12-14 | 2013-05-15 | Enanta Pharm Inc | HEPATITIS C-VIRUS HEMMER |
| 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 |
| CN102753173A (zh) | 2009-12-18 | 2012-10-24 | 贝林格尔.英格海姆国际有限公司 | Hcv组合疗法 |
| CA2784748A1 (en) * | 2009-12-18 | 2011-06-23 | Idenix Pharmaceuticals, Inc. | 5,5-fused arylene or heteroarylene hepatitis c virus inhibitors |
| WO2011087740A1 (en) | 2009-12-22 | 2011-07-21 | Schering Corporation | Fused tricyclic compounds and methods of use thereof for the treatment of viral diseases |
| US20130072523A1 (en) * | 2009-12-24 | 2013-03-21 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
| US8362020B2 (en) | 2009-12-30 | 2013-01-29 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8933110B2 (en) | 2010-01-25 | 2015-01-13 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| PE20130244A1 (es) * | 2010-01-25 | 2013-03-10 | Enanta Pharm Inc | Inhibidores del virus de la hepatitis c |
| JP2013518062A (ja) * | 2010-01-28 | 2013-05-20 | 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型肝炎阻害化合物 |
| US8178531B2 (en) | 2010-02-23 | 2012-05-15 | Enanta Pharmaceuticals, Inc. | Antiviral agents |
| US8623814B2 (en) | 2010-02-23 | 2014-01-07 | Enanta Pharmaceuticals, Inc. | Antiviral agents |
| WO2011109037A1 (en) | 2010-03-04 | 2011-09-09 | Enanta Pharmaceuticals, Inc. | Combination pharmaceutical agents as inhibitors of hcv replication |
| CN102918049A (zh) | 2010-03-09 | 2013-02-06 | 默沙东公司 | 稠合三环甲硅烷基化合物及其用于治疗病毒性疾病的方法 |
| TW201139438A (en) * | 2010-03-24 | 2011-11-16 | Vertex Pharma | Analogues for the treatment or prevention of flavivirus infections |
| 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 |
| WO2011127350A1 (en) | 2010-04-09 | 2011-10-13 | Enanta Pharmaceuticals, Inc. | Hepatitis c virus 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 |
| WO2012006060A1 (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 |
| JP5826269B2 (ja) | 2010-07-26 | 2015-12-02 | ヤンセン・サイエンシズ・アイルランド・ユーシー | Ｈｃｖ阻害剤としてのヘテロ−二環式誘導体 |
| US20140377223A1 (en) | 2010-07-26 | 2014-12-25 | Joseph A. Kozlowski | Substituted biphenylene compounds and methods of use thereof for the treatment of viral diseases |
| US20120195857A1 (en) * | 2010-08-12 | 2012-08-02 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US8697704B2 (en) | 2010-08-12 | 2014-04-15 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| 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 |
| BR112013004520A2 (pt) | 2010-08-26 | 2016-06-07 | Univ Emory | inibidores potentes e seletivos do virus da hepatite c |
| US8822520B2 (en) | 2010-09-22 | 2014-09-02 | Presidio Pharmaceuticals, Inc. | Substituted bicyclic HCV inhibitors |
| WO2012041227A1 (en) * | 2010-09-29 | 2012-04-05 | Merck Sharp & Dohme Corp. | Tetracyclic heterocycle compounds for treating hepatitis c viral infection |
| WO2012050918A2 (en) | 2010-09-29 | 2012-04-19 | Presidio Pharmaceutical, Inc. | Tricyclic fused ring inhibitors of hepatitis c |
| 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 |
| SG189985A1 (en) | 2010-10-26 | 2013-06-28 | Presidio Pharmaceuticals Inc | Inhibitors of hepatitis c virus |
| CN103189371B (zh) | 2010-11-04 | 2015-04-01 | 施万生物制药研发Ip有限责任公司 | 丙型肝炎病毒抑制剂 |
| TWI548629B (zh) * | 2010-11-17 | 2016-09-11 | 吉李德製藥公司 | 抗病毒化合物 |
| RU2452735C1 (ru) * | 2010-11-30 | 2012-06-10 | Александр Васильевич Иващенко | Замещенные азолы, противовирусный активный компонент, фармацевтическая композиция, способ получения и применения |
| WO2012083059A1 (en) * | 2010-12-15 | 2012-06-21 | Abbott Laboratories | Anti-viral compounds |
| US20150031884A1 (en) * | 2010-12-15 | 2015-01-29 | Abbvie Inc. | Anti-viral compounds |
| EP2655334B1 (en) | 2010-12-22 | 2018-10-03 | Eutropics Pharmaceuticals, Inc. | Compositions and methods useful for treating diseases |
| EP2655362A1 (en) | 2010-12-22 | 2013-10-30 | Abbvie Inc. | Hepatitis c inhibitors and uses thereof |
| 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 |
| 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 |
| 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 |
| FR2981071B1 (fr) * | 2011-10-10 | 2014-02-07 | Centre Nat Rech Scient | Synthese versatile et stereospecifique d'acides amines gamma,delta-insatures par la reaction de wittig |
| WO2013030750A1 (en) | 2011-09-01 | 2013-03-07 | Lupin Limited | Antiviral compounds |
| EP2755981A4 (en) | 2011-09-14 | 2015-03-25 | Merck Sharp & Dohme | SILICULAR HETEROCYCLIC DERIVATIVES AND METHOD FOR THEIR USE FOR THE TREATMENT OF VIRUS DISEASES |
| CA2840242C (en) | 2011-09-16 | 2019-03-26 | Gilead Sciences, Inc. | Methods for treating hcv |
| US8957048B2 (en) | 2011-10-06 | 2015-02-17 | Allergan, Inc. | Compositions for the treatment of dry eye |
| US9212168B2 (en) | 2011-11-03 | 2015-12-15 | Theravance Biopharma R&D Ip, Llc | Hepatitis C virus inhibitors |
| PL2635588T3 (pl) | 2011-11-16 | 2015-10-30 | Gilead Pharmasset Llc | Skondensowane imidazoliloimidazole jako związki antywirusowe |
| 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 |
| US9907826B2 (en) | 2011-12-07 | 2018-03-06 | Allergan, Inc. | Efficient lipid delivery to human tear film using a salt-sensitive emulsion system |
| WO2013098313A1 (en) | 2011-12-28 | 2013-07-04 | Janssen R&D Ireland | Hetero-bicyclic derivatives as hcv inhibitors |
| JP6199891B2 (ja) * | 2011-12-28 | 2017-09-20 | ヤンセン・サイエンシズ・アイルランド・ユーシー | Ｈｃｖ阻害剤としてのキナゾリノン誘導体 |
| 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 |
| AU2013217224B2 (en) | 2012-02-10 | 2017-04-06 | Lupin Limited | Antiviral compounds with a dibenzooxaheterocycle moiety |
| US9012427B2 (en) | 2012-03-22 | 2015-04-21 | Alios Biopharma, Inc. | Pharmaceutical combinations comprising a thionucleotide analog |
| CA2869908C (en) | 2012-04-25 | 2018-02-20 | Theravance Biopharma R&D Ip, Llc | Hepatitis c virus inhibitors |
| CA2869640C (en) | 2012-04-25 | 2018-03-20 | Theravance Biopharma R&D Ip, Llc | Piperazine-piperidine compounds as hepatitis c virus inhibitors |
| US20130309196A1 (en) | 2012-05-16 | 2013-11-21 | Gilead Sciences, Inc. | Antiviral compounds |
| US9216991B2 (en) * | 2012-07-10 | 2015-12-22 | Ares Trading S.A. | Pyrimidine pyrazolyl derivatives |
| 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 |
| CN103848818B (zh) | 2012-11-29 | 2017-03-15 | 广东东阳光药业有限公司 | 作为丙型肝炎抑制剂的并环化合物、药物组合物及它们在药物中的应用 |
| US9416139B2 (en) | 2012-11-29 | 2016-08-16 | Sunshine Lake Pharma Co., Ltd. | Spiro ring compound as hepatitis C virus (HCV) inhibitor and uses thereof |
| KR20200060782A (ko) | 2013-01-31 | 2020-06-01 | 길리애드 파마셋 엘엘씨 | 두 항바이러스 화합물의 병용 제형물 |
| RU2507201C1 (ru) * | 2013-02-07 | 2014-02-20 | Александр Васильевич Иващенко | Алкил [(s)-1-((s)-2-{5-[4-(4-{2-[(s)-1-((s)-2-метоксикарбониламино-3-метил-бутирил)-пирролидин-2-ил]-3н-имидазол-4-ил}-бута-1,3-диинил)-фенил]-1н-имидазол-2-ил}-пирролидин-1-карбонил)-2-метил-пропил]-карбамат нафталин-1,5-дисульфонат, фармацевтическая композиция, лекарственное средство, способ лечения вирусных заболеваний |
| TW201526899A (zh) | 2013-02-28 | 2015-07-16 | Alios Biopharma Inc | 醫藥組成物 |
| US11484534B2 (en) | 2013-03-14 | 2022-11-01 | Abbvie Inc. | Methods for treating HCV |
| US20150023913A1 (en) | 2013-07-02 | 2015-01-22 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| 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 |
| WO2015009744A1 (en) | 2013-07-17 | 2015-01-22 | Bristol-Myers Squibb Company | Combinations comprising biphenyl derivatives for use in the treatment of hcv |
| EP3650014B1 (en) | 2013-08-27 | 2021-10-06 | Gilead Pharmasset LLC | Combination formulation of two antiviral compounds |
| EP3063140A4 (en) | 2013-10-30 | 2017-11-08 | 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 |
| 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 |
| US20170327457A1 (en) | 2014-09-09 | 2017-11-16 | Bristol-Myers Squibb Company | Phenyl-(aza)cycloalkyl carboxylic acid gpr120 modulators |
| US10617675B2 (en) | 2015-08-06 | 2020-04-14 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| GB2552919A (en) * | 2015-11-18 | 2018-02-21 | Azad Pharmaceutical Ingredients Ag | Stable amorphous form of daclatasvir |
| RU2650610C1 (ru) | 2017-02-28 | 2018-04-16 | Васильевич Иващенко Александр | Противовирусная композиция и способ ее применения |
| US20220099637A1 (en) | 2018-12-04 | 2022-03-31 | Bristol-Myers Squibb Company | Methods of analysis using in-sample calibration curve by multiple isotopologue reaction monitoring |
| CN109456375B (zh) * | 2018-12-11 | 2019-10-22 | 枣庄学院 | 一种抑制丙肝病毒的含单糖基杂环类化合物及制备方法 |
| CA3220903A1 (en) | 2021-05-21 | 2022-11-24 | Gilead Sciences, Inc. | Pentacyclic derivatives as zika virus inhibitors |
Family Cites Families (22)
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|---|---|---|---|---|
| EP0679153A4 (en) | 1993-01-14 | 1996-05-15 | Magainin Pharma | FINALLY MODIFIED AMINO ACIDS AND PEPTIDES. |
| US5654451B1 (en) | 1993-01-14 | 2000-02-22 | Magainin Pharma | Amino acids and peptides having modified c-terminals and modified n-terminals |
| WO1998027108A2 (en) * | 1996-12-16 | 1998-06-25 | Fujisawa Pharmaceutical Co., Ltd. | New amide compounds and their use as nitric oxide synthase inhibitors |
| US7244721B2 (en) * | 2000-07-21 | 2007-07-17 | Schering Corporation | Peptides as NS3-serine protease inhibitors of hepatitis C virus |
| MXPA05000255A (es) | 2002-07-01 | 2005-07-15 | Pharmacia & Upjohn Co Llc | Inhibidores de polimerasa de ns5b de hcv. |
| AU2003249977A1 (en) * | 2002-07-05 | 2004-01-23 | Axxima Pharmaceuticals Ag | Imidazole compounds for the treatment of hepatitis c virus infections |
| US7220745B2 (en) | 2003-05-15 | 2007-05-22 | Rigel Pharmaceuticals | Heterocyclic compounds useful to treat HCV |
| US20050119318A1 (en) | 2003-10-31 | 2005-06-02 | Hudyma Thomas W. | Inhibitors of HCV replication |
| GB0326168D0 (en) | 2003-11-10 | 2003-12-17 | Arrow Therapeutics Ltd | Chemical compounds |
| EP1748991A1 (en) | 2004-04-28 | 2007-02-07 | Arrow Therapeutics Limited | Morpholinylanilinoquinazo- line derivatives for use as antiviral agents |
| WO2006022442A1 (ja) | 2004-08-24 | 2006-03-02 | Santen Pharmaceutical Co., Ltd. | ジヒドロオロテートデヒドロゲナーゼ阻害活性を有する新規複素環アミド誘導体 |
| WO2006093867A1 (en) | 2005-02-28 | 2006-09-08 | The Rockefeller University | Structure of the hepatitits c virus ns5a protein |
| US8143288B2 (en) | 2005-06-06 | 2012-03-27 | Bristol-Myers Squibb Company | Inhibitors of HCV replication |
| RS51470B (sr) | 2005-09-16 | 2011-04-30 | Arrow Therapeutics Limited | Derivati bifenila i njihova upotreba za lečenje hepatitisa c |
| WO2007058384A1 (en) | 2005-11-17 | 2007-05-24 | Osaka University | Method of suppressing replication of hepatitis c virus, inhibitor of replication of the virus and method of screening for the same |
| WO2007081517A2 (en) | 2005-12-21 | 2007-07-19 | Abbott Laboratories | Anti-viral compounds |
| SG133452A1 (en) | 2005-12-30 | 2007-07-30 | Novartis Ag | Peptide deformylase inhibitors for treatment of mycobacterial and other parasitic diseases |
| BRPI0706412A2 (pt) | 2006-01-11 | 2011-03-29 | Arrow Therapeutics Ltd | composto, uso de um composto, produto, composição farmacêutica, uso de um interferon ou um derivado de interferon, e, método de tratamento de um paciente sofrendo ou susceptìvel a infecção por flaviviridae |
| WO2007082554A1 (en) | 2006-01-23 | 2007-07-26 | Istituto Di Ricerche Di Biologia Molecolare P Angeletti Spa | Modulators of hcv replication |
| EP2038253A1 (en) | 2006-05-30 | 2009-03-25 | Arrow Therapeutics Limited | Biphenyl derivatives and their use in treating hepatitis c |
| US7759495B2 (en) | 2006-08-11 | 2010-07-20 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8329159B2 (en) | 2006-08-11 | 2012-12-11 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
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| AU2007286223A1 (en) | 2008-02-21 |
| US20080044379A1 (en) | 2008-02-21 |
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| US7659270B2 (en) | 2010-02-09 |
| NO20090453L (no) | 2009-03-09 |
| CN101528232B (zh) | 2014-11-12 |
| ZA200900935B (en) | 2010-03-31 |
| KR20090040910A (ko) | 2009-04-27 |
| IL196815A0 (en) | 2009-11-18 |
| EP2049116B1 (en) | 2012-02-29 |
| EP2049116A2 (en) | 2009-04-22 |
| IL196815A (en) | 2013-08-29 |
| JP2010500414A (ja) | 2010-01-07 |
| KR101438851B1 (ko) | 2014-09-11 |
| ES2382005T3 (es) | 2012-06-04 |
| HK1125576A1 (en) | 2009-08-14 |
| AU2007286223B2 (en) | 2012-06-21 |
| CA2660628C (en) | 2014-10-28 |
| JP5306203B2 (ja) | 2013-10-02 |
| NZ574769A (en) | 2011-07-29 |
| WO2008021928A2 (en) | 2008-02-21 |
| WO2008021928A3 (en) | 2008-03-27 |
| EA200900297A1 (ru) | 2009-08-28 |
| EA017348B1 (ru) | 2012-11-30 |
| CN101528232A (zh) | 2009-09-09 |
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