CA2814534A1 - Novel inhibitors of hepatitis c virus - Google Patents
Novel inhibitors of hepatitis c virus Download PDFInfo
- Publication number
- CA2814534A1 CA2814534A1 CA2814534A CA2814534A CA2814534A1 CA 2814534 A1 CA2814534 A1 CA 2814534A1 CA 2814534 A CA2814534 A CA 2814534A CA 2814534 A CA2814534 A CA 2814534A CA 2814534 A1 CA2814534 A1 CA 2814534A1
- Authority
- CA
- Canada
- Prior art keywords
- 6alkyl
- 3alkyl
- mmol
- optionally substituted
- methyl
- 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.)
- Abandoned
Links
- 241000711549 Hepacivirus C Species 0.000 title claims abstract description 55
- 239000003112 inhibitor Substances 0.000 title claims abstract description 21
- 150000001875 compounds Chemical class 0.000 claims abstract description 288
- 238000000034 method Methods 0.000 claims abstract description 109
- 150000003839 salts Chemical class 0.000 claims abstract description 53
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 41
- 208000005176 Hepatitis C Diseases 0.000 claims abstract description 20
- 208000036142 Viral infection Diseases 0.000 claims abstract description 19
- 230000009385 viral infection Effects 0.000 claims abstract description 19
- 230000010076 replication Effects 0.000 claims abstract description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 323
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 120
- 229910052739 hydrogen Inorganic materials 0.000 claims description 87
- 239000001257 hydrogen Substances 0.000 claims description 86
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 71
- 229910052757 nitrogen Inorganic materials 0.000 claims description 69
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 69
- -1 -CH2-heteroaryl Chemical group 0.000 claims description 57
- 125000000623 heterocyclic group Chemical group 0.000 claims description 45
- 125000005843 halogen group Chemical group 0.000 claims description 44
- 125000001072 heteroaryl group Chemical group 0.000 claims description 38
- 241000124008 Mammalia Species 0.000 claims description 35
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
- 229910052799 carbon Inorganic materials 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 29
- 150000002431 hydrogen Chemical group 0.000 claims description 29
- 108010050904 Interferons Proteins 0.000 claims description 28
- 102000014150 Interferons Human genes 0.000 claims description 28
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 28
- 239000002777 nucleoside Substances 0.000 claims description 28
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 24
- 239000003814 drug Substances 0.000 claims description 19
- 229940124597 therapeutic agent Drugs 0.000 claims description 18
- 229940047124 interferons Drugs 0.000 claims description 17
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 17
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 16
- 229960000329 ribavirin Drugs 0.000 claims description 16
- 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 16
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 13
- 239000003937 drug carrier Substances 0.000 claims description 11
- 108700008776 hepatitis C virus NS-5 Proteins 0.000 claims description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 150000001721 carbon Chemical group 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- 229940124771 HCV-NS3 protease inhibitor Drugs 0.000 claims description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 125000006413 ring segment Chemical group 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- DODHZNAXGLNLGI-UHFFFAOYSA-N 1-cyclopropyl-2-methylpyrrolidine Chemical compound CC1CCCN1C1CC1 DODHZNAXGLNLGI-UHFFFAOYSA-N 0.000 claims description 2
- KOBDKUVEIRTGAJ-UHFFFAOYSA-N methyl 2-methylpyrrolidine-1-carboxylate Chemical compound COC(=O)N1CCCC1C KOBDKUVEIRTGAJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 66
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 40
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 18
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 2
- DYEXGZBLHUAIJJ-UHFFFAOYSA-N 1-(2,2-dimethylcyclopropyl)-2-methylpyrrolidine Chemical compound CC1CCCN1C1C(C)(C)C1 DYEXGZBLHUAIJJ-UHFFFAOYSA-N 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 136
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- 238000002360 preparation method Methods 0.000 description 146
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 138
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 126
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- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 53
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- 239000012044 organic layer Substances 0.000 description 48
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- 229910052938 sodium sulfate Inorganic materials 0.000 description 46
- 235000011152 sodium sulphate Nutrition 0.000 description 46
- 238000002953 preparative HPLC Methods 0.000 description 44
- 239000007821 HATU Substances 0.000 description 43
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 37
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 35
- 238000010898 silica gel chromatography Methods 0.000 description 35
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 33
- 239000003153 chemical reaction reagent Substances 0.000 description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- 238000005160 1H NMR spectroscopy Methods 0.000 description 28
- 238000006243 chemical reaction Methods 0.000 description 28
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 27
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- 238000004007 reversed phase HPLC Methods 0.000 description 24
- 238000003556 assay Methods 0.000 description 23
- 238000002390 rotary evaporation Methods 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 239000012267 brine Substances 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
- DEKJPODSYVPCPW-ZGZXFVETSA-N 4-(aminomethyl)-N-[(12E,15S)-17,19-diazatricyclo[14.2.1.02,7]nonadeca-1(18),2,4,6,12,16-hexaen-15-yl]cyclohexane-1-carboxamide Chemical compound NCC1CCC(CC1)C(=O)N[C@H]1C\C=C\CCCCc2ccccc2-c2cnc1[nH]2 DEKJPODSYVPCPW-ZGZXFVETSA-N 0.000 description 18
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
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- 101150041968 CDC13 gene Proteins 0.000 description 14
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- BFNMOMYTTGHNGJ-SCSAIBSYSA-N (1s)-2,2-dimethylcyclopropane-1-carboxylic acid Chemical compound CC1(C)C[C@@H]1C(O)=O BFNMOMYTTGHNGJ-SCSAIBSYSA-N 0.000 description 12
- IPOCOANFUVSCLZ-UHFFFAOYSA-N 6-fluoropyridine-3-carbonyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=N1 IPOCOANFUVSCLZ-UHFFFAOYSA-N 0.000 description 12
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- IYWRCNFZPNEADN-CXODAYGWSA-N tert-butyl n-[(2s)-1-[(2s,4r)-2-[[(1r,2s)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]carbamoyl]-4-(6-methoxyisoquinolin-1-yl)oxypyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC=1C2=CC=C(C=C2C=CN=1)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C IYWRCNFZPNEADN-CXODAYGWSA-N 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- 239000012414 tert-butyl nitrite Substances 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 229960000984 tocofersolan Drugs 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
- 230000000699 topical effect Effects 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000005591 trimellitate group Chemical group 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Substances C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000017613 viral reproduction Effects 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- 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
- C07D403/14—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)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gastroenterology & Hepatology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (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)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41026710P | 2010-11-04 | 2010-11-04 | |
| US61/410,267 | 2010-11-04 | ||
| US201161444046P | 2011-02-17 | 2011-02-17 | |
| US61/444,046 | 2011-02-17 | ||
| US201161492267P | 2011-06-01 | 2011-06-01 | |
| US61/492,267 | 2011-06-01 | ||
| PCT/US2011/059061 WO2012061552A1 (en) | 2010-11-04 | 2011-11-03 | Novel inhibitors of hepatitis c virus |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2814534A1 true CA2814534A1 (en) | 2012-05-10 |
Family
ID=44993923
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2814534A Abandoned CA2814534A1 (en) | 2010-11-04 | 2011-11-03 | Novel inhibitors of hepatitis c virus |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US8921372B2 (enExample) |
| EP (1) | EP2635571B1 (enExample) |
| JP (1) | JP5891235B2 (enExample) |
| CN (1) | CN103189371B (enExample) |
| AR (1) | AR083757A1 (enExample) |
| CA (1) | CA2814534A1 (enExample) |
| ES (1) | ES2548286T3 (enExample) |
| TW (1) | TW201249827A (enExample) |
| WO (1) | WO2012061552A1 (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8921732B2 (en) * | 2007-06-12 | 2014-12-30 | Revolaze, LLC | High speed and high power laser scribing methods and systems |
| PL2368890T3 (pl) | 2009-06-11 | 2013-10-31 | Abbvie Bahamas Ltd | Inhibitory wirusa zapalenia wątroby C |
| US8937150B2 (en) | 2009-06-11 | 2015-01-20 | Abbvie Inc. | Anti-viral compounds |
| NZ605440A (en) | 2010-06-10 | 2014-05-30 | Abbvie Bahamas Ltd | Solid compositions comprising an hcv inhibitor |
| WO2012061552A1 (en) * | 2010-11-04 | 2012-05-10 | Theravance, Inc. | Novel inhibitors of hepatitis c virus |
| US8552047B2 (en) | 2011-02-07 | 2013-10-08 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| 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 |
| PE20141531A1 (es) | 2011-06-22 | 2014-10-23 | Purdue Pharma Lp | Antagonistas de trpv1 que incluyen sustituyentes dihidroxi y sus usos |
| BR112014010401A8 (pt) * | 2011-11-03 | 2017-12-19 | Theravance Inc | Inibidores do vírus da hepatite c rod-like que contêm o fragmento {2-[4-(bifenil-4-il)-1h-imidazo-2-il] pirrolidina-1-carbonilmetil}amina |
| 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 |
| JP6069492B2 (ja) * | 2012-04-25 | 2017-02-01 | セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー | Ｃ型肝炎ウイルス阻害剤 |
| WO2013163262A1 (en) | 2012-04-25 | 2013-10-31 | Theravance, Inc. | Piperazine-piperidine compounds as hepatitis c virus inhibitors |
| WO2013165796A1 (en) * | 2012-05-03 | 2013-11-07 | Theravance, Inc. | Crystalline form of a pyridyl-piperazinyl hepatitis c virus inhibitor |
| 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 |
| US9775831B2 (en) | 2013-07-17 | 2017-10-03 | Bristol-Myers Squibb Company | Combinations comprising biphenyl derivatives for use in the treatment of HCV |
| WO2015103490A1 (en) | 2014-01-03 | 2015-07-09 | Abbvie, Inc. | Solid antiviral dosage forms |
| US10617675B2 (en) | 2015-08-06 | 2020-04-14 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CN105175401A (zh) * | 2015-10-16 | 2015-12-23 | 北京康立生医药技术开发有限公司 | 一种依匹哌唑的制备方法 |
| CN112409336B (zh) * | 2017-11-27 | 2021-09-14 | 常州寅盛药业有限公司 | 适于工业化生产的达卡他韦起始原料的合成方法 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0421908D0 (en) * | 2004-10-01 | 2004-11-03 | Angeletti P Ist Richerche Bio | New uses |
| DK1940786T3 (da) * | 2005-09-16 | 2010-11-08 | Arrow Therapeutics Ltd | Biphenylderivater og deres anvendelse ved behandling af hepatitis C |
| US8329159B2 (en) * | 2006-08-11 | 2012-12-11 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7745636B2 (en) | 2006-08-11 | 2010-06-29 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7659270B2 (en) | 2006-08-11 | 2010-02-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8303944B2 (en) | 2006-08-11 | 2012-11-06 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CN101558059B (zh) * | 2006-08-11 | 2014-12-03 | 百时美施贵宝公司 | 丙型肝炎病毒抑制剂 |
| US7910722B2 (en) * | 2007-07-05 | 2011-03-22 | Florida State University Research Foundation | RNAi therapeutic for treatment of hepatitis C infection |
| AU2008350327B2 (en) | 2008-02-12 | 2013-09-12 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CA2750577A1 (en) | 2008-12-03 | 2010-06-10 | Presidio Pharmaceuticals, Inc. | Inhibitors of hcv ns5a |
| WO2010096777A1 (en) | 2009-02-23 | 2010-08-26 | Presidio Pharmaceuticals, Inc. | Inhibitors of hcv ns5a |
| UY32462A (es) * | 2009-02-23 | 2010-09-30 | Arrow Therapeutics Ltd | Derivados de bifenilo novedosos para el tratamiento de infección por virus de hepatitis c 644 |
| 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 |
| 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 |
| US8778938B2 (en) | 2010-06-04 | 2014-07-15 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| WO2012061552A1 (en) * | 2010-11-04 | 2012-05-10 | Theravance, Inc. | Novel inhibitors of hepatitis c virus |
| BR112014010401A8 (pt) | 2011-11-03 | 2017-12-19 | Theravance Inc | Inibidores do vírus da hepatite c rod-like que contêm o fragmento {2-[4-(bifenil-4-il)-1h-imidazo-2-il] pirrolidina-1-carbonilmetil}amina |
-
2011
- 2011-11-03 WO PCT/US2011/059061 patent/WO2012061552A1/en not_active Ceased
- 2011-11-03 CN CN201180053127.4A patent/CN103189371B/zh not_active Expired - Fee Related
- 2011-11-03 ES ES11784875.4T patent/ES2548286T3/es active Active
- 2011-11-03 JP JP2013537808A patent/JP5891235B2/ja not_active Expired - Fee Related
- 2011-11-03 CA CA2814534A patent/CA2814534A1/en not_active Abandoned
- 2011-11-03 US US13/288,216 patent/US8921372B2/en not_active Expired - Fee Related
- 2011-11-03 EP EP11784875.4A patent/EP2635571B1/en active Active
- 2011-11-04 TW TW100140412A patent/TW201249827A/zh unknown
- 2011-11-04 AR ARP110104114A patent/AR083757A1/es not_active Application Discontinuation
-
2014
- 2014-11-12 US US14/539,039 patent/US9260414B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP5891235B2 (ja) | 2016-03-22 |
| CN103189371B (zh) | 2015-04-01 |
| JP2013544812A (ja) | 2013-12-19 |
| TW201249827A (en) | 2012-12-16 |
| US8921372B2 (en) | 2014-12-30 |
| EP2635571B1 (en) | 2015-08-12 |
| EP2635571A1 (en) | 2013-09-11 |
| US20150071878A1 (en) | 2015-03-12 |
| WO2012061552A1 (en) | 2012-05-10 |
| US20120114600A1 (en) | 2012-05-10 |
| ES2548286T3 (es) | 2015-10-15 |
| CN103189371A (zh) | 2013-07-03 |
| US9260414B2 (en) | 2016-02-16 |
| AR083757A1 (es) | 2013-03-20 |
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| NZ623846B2 (en) | Rod-like hepatitis c virus inhibitors containing the fragment {2-[4-(bi phenyl-4-yl) -1h-imidazo-2-yl] pyrrolidine-1-carbonlymethyl} amine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20160518 |
|
| FZDE | Dead |
Effective date: 20190620 |