MX2011010132A - Inhibidores de anillo fusionado de hepatitis c. - Google Patents
Inhibidores de anillo fusionado de hepatitis c.Info
- Publication number
- MX2011010132A MX2011010132A MX2011010132A MX2011010132A MX2011010132A MX 2011010132 A MX2011010132 A MX 2011010132A MX 2011010132 A MX2011010132 A MX 2011010132A MX 2011010132 A MX2011010132 A MX 2011010132A MX 2011010132 A MX2011010132 A MX 2011010132A
- Authority
- MX
- Mexico
- Prior art keywords
- compound
- group
- heterocycle
- heteroaryl
- cycloalkyl
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title description 24
- 208000006454 hepatitis Diseases 0.000 title description 3
- 231100000283 hepatitis Toxicity 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 251
- 238000011282 treatment Methods 0.000 claims abstract description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 208000005176 Hepatitis C Diseases 0.000 claims abstract description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 345
- 125000001072 heteroaryl group Chemical group 0.000 claims description 266
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 247
- 125000003118 aryl group Chemical group 0.000 claims description 237
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 231
- 229910052739 hydrogen Inorganic materials 0.000 claims description 157
- 239000001257 hydrogen Substances 0.000 claims description 141
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 129
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 109
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 107
- 125000003545 alkoxy group Chemical group 0.000 claims description 106
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 106
- 125000001589 carboacyl group Chemical group 0.000 claims description 106
- 150000002431 hydrogen Chemical class 0.000 claims description 106
- 229940124530 sulfonamide Drugs 0.000 claims description 105
- 150000003456 sulfonamides Chemical class 0.000 claims description 105
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 105
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 104
- -1 -OH Chemical group 0.000 claims description 103
- 125000006539 C12 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 101
- 229910052736 halogen Inorganic materials 0.000 claims description 78
- 150000002367 halogens Chemical class 0.000 claims description 78
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 75
- 229910052799 carbon Inorganic materials 0.000 claims description 67
- 229910052721 tungsten Inorganic materials 0.000 claims description 64
- 125000005842 heteroatom Chemical group 0.000 claims description 57
- 229910052702 rhenium Inorganic materials 0.000 claims description 57
- 238000000034 method Methods 0.000 claims description 54
- 229910052717 sulfur Inorganic materials 0.000 claims description 54
- 229910052760 oxygen Inorganic materials 0.000 claims description 51
- 229910052727 yttrium Inorganic materials 0.000 claims description 46
- 125000001424 substituent group Chemical group 0.000 claims description 44
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 42
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- 150000001413 amino acids Chemical class 0.000 claims description 31
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 7
- 125000002950 monocyclic group Chemical group 0.000 claims description 7
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 107
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 68
- 125000004093 cyano group Chemical group *C#N 0.000 description 66
- CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 description 62
- 239000000243 solution Substances 0.000 description 61
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- 238000002360 preparation method Methods 0.000 description 30
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- 239000000047 product Substances 0.000 description 21
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- 238000005481 NMR spectroscopy Methods 0.000 description 18
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- 125000000392 cycloalkenyl group Chemical group 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
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- 239000003795 chemical substances by application Substances 0.000 description 11
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- 238000010511 deprotection reaction Methods 0.000 description 11
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- 238000003818 flash chromatography Methods 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- 108010050904 Interferons Proteins 0.000 description 9
- 102000014150 Interferons Human genes 0.000 description 9
- 239000007832 Na2SO4 Substances 0.000 description 9
- 101800001014 Non-structural protein 5A Proteins 0.000 description 9
- 229910019142 PO4 Inorganic materials 0.000 description 9
- 150000001408 amides Chemical class 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 229910052681 coesite Inorganic materials 0.000 description 9
- 229910052906 cristobalite Inorganic materials 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000005755 formation reaction Methods 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 9
- 239000010452 phosphate Substances 0.000 description 9
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 9
- 229910052682 stishovite Inorganic materials 0.000 description 9
- 229910052905 tridymite Inorganic materials 0.000 description 9
- 239000003039 volatile agent Substances 0.000 description 9
- AZUHIVLOSAPWDM-UHFFFAOYSA-N 2-(1h-imidazol-2-yl)-1h-imidazole Chemical compound C1=CNC(C=2NC=CN=2)=N1 AZUHIVLOSAPWDM-UHFFFAOYSA-N 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
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- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 8
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- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 7
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- 229940079322 interferon Drugs 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
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- YUHZIUAREWNXJT-UHFFFAOYSA-N (2-fluoropyridin-3-yl)boronic acid Chemical class OB(O)C1=CC=CN=C1F YUHZIUAREWNXJT-UHFFFAOYSA-N 0.000 description 6
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 6
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
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- FMPGUGGAUQSWEU-UHFFFAOYSA-N 2,6-dibromoxanthen-9-one Chemical compound C1=C(Br)C=C2C(=O)C3=CC=C(Br)C=C3OC2=C1 FMPGUGGAUQSWEU-UHFFFAOYSA-N 0.000 description 5
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- 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
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Classifications
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- 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
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- 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
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- 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
- 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
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- 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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
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| US16434209P | 2009-03-27 | 2009-03-27 | |
| US21488309P | 2009-04-28 | 2009-04-28 | |
| PCT/US2010/028730 WO2010111534A1 (en) | 2009-03-27 | 2010-03-25 | Fused ring inhibitors of hepatitis c |
Publications (1)
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| MX2011010132A true MX2011010132A (es) | 2011-10-14 |
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| MX2011010132A MX2011010132A (es) | 2009-03-27 | 2010-03-25 | Inhibidores de anillo fusionado de hepatitis c. |
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| EP (1) | EP2410843A4 (enExample) |
| JP (1) | JP5735482B2 (enExample) |
| KR (1) | KR20110131312A (enExample) |
| CN (1) | CN102427726B (enExample) |
| AR (1) | AR076164A1 (enExample) |
| AU (1) | AU2010229795A1 (enExample) |
| BR (1) | BRPI1012282A2 (enExample) |
| CA (1) | CA2755658A1 (enExample) |
| CL (1) | CL2011002377A1 (enExample) |
| CO (1) | CO6450600A2 (enExample) |
| EA (1) | EA201190224A1 (enExample) |
| IL (1) | IL215202A0 (enExample) |
| MX (1) | MX2011010132A (enExample) |
| PE (1) | PE20120773A1 (enExample) |
| SG (1) | SG174883A1 (enExample) |
| TW (1) | TW201038560A (enExample) |
| WO (1) | WO2010111534A1 (enExample) |
| ZA (1) | ZA201107753B (enExample) |
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| RU2505539C2 (ru) | 2008-12-23 | 2014-01-27 | Эбботт Лэборетриз | Антивирусные соединения |
| US8541424B2 (en) | 2008-12-23 | 2013-09-24 | Abbott Laboratories | Anti-viral compounds |
| US8314135B2 (en) | 2009-02-09 | 2012-11-20 | Enanta Pharmaceuticals, Inc. | Linked dibenzimidazole antivirals |
| US8394968B2 (en) | 2009-02-17 | 2013-03-12 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8188132B2 (en) | 2009-02-17 | 2012-05-29 | Enanta Pharmaceuticals, Inc. | Linked dibenzimidazole derivatives |
| US8242156B2 (en) | 2009-02-17 | 2012-08-14 | Enanta Pharmaceuticals, Inc. | Linked dibenzimidazole derivatives |
| US8673954B2 (en) | 2009-02-27 | 2014-03-18 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
| US8101643B2 (en) | 2009-02-27 | 2012-01-24 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
| US9765087B2 (en) | 2009-02-27 | 2017-09-19 | Enanta Pharmaceuticals, Inc. | Benzimidazole derivatives |
| US8507522B2 (en) | 2009-03-06 | 2013-08-13 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| AU2010229795A1 (en) | 2009-03-27 | 2011-10-13 | Presidio Pharmaceuticals, Inc. | Fused ring inhibitors of hepatitis C |
| US20190127365A1 (en) | 2017-11-01 | 2019-05-02 | Merck Sharp & Dohme Corp. | Inhibitors of hepatitis c virus replication |
| SG10201402969QA (en) | 2009-03-27 | 2014-09-26 | Merck Sharp & Dohme | Inhibitors of hepatitis c virus replication |
| 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 |
| JP5734956B2 (ja) | 2009-04-15 | 2015-06-17 | アッヴィ・インコーポレイテッド | 抗ウィルス化合物 |
| AU2010249080A1 (en) * | 2009-05-12 | 2012-01-12 | Merck Sharp & Dohme Corp. | Fused tricyclic aryl compounds useful for the treatment of viral diseases |
| NZ619205A (en) | 2009-05-13 | 2015-04-24 | Gilead Pharmasset Llc | Antiviral compounds |
| 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 |
| PL2368890T3 (pl) | 2009-06-11 | 2013-10-31 | Abbvie Bahamas Ltd | Inhibitory wirusa zapalenia wątroby C |
| 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 |
| US8716454B2 (en) | 2009-06-11 | 2014-05-06 | Abbvie Inc. | Solid compositions |
| 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 |
| JP2012533569A (ja) | 2009-07-16 | 2012-12-27 | ヴァーテックス 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症を治療又は予防するためのベンゾイミダゾール類似体 |
| CN102725290B (zh) | 2009-07-27 | 2016-03-09 | 吉利德科学股份有限公司 | 作为离子通道调节剂的稠合杂环化合物 |
| NZ597982A (en) | 2009-09-04 | 2013-01-25 | Glaxosmithkline Llc | CHEMICAL COMPOUNDS for treating Hepatitis C virus |
| US8703938B2 (en) | 2009-09-11 | 2014-04-22 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| WO2011031904A1 (en) | 2009-09-11 | 2011-03-17 | Enanta Pharmaceuticals, Inc | Hepatitis c virus inhibitors |
| US8759332B2 (en) | 2009-09-11 | 2014-06-24 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8927709B2 (en) | 2009-09-11 | 2015-01-06 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8815928B2 (en) | 2009-09-11 | 2014-08-26 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8822700B2 (en) | 2009-09-11 | 2014-09-02 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| 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 |
| 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 |
| CN102791687B (zh) * | 2009-12-18 | 2015-02-11 | 北京凯因科技股份有限公司 | C型肝炎病毒复制的新型抑制剂 |
| US8362020B2 (en) | 2009-12-30 | 2013-01-29 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| MX2012008658A (es) | 2010-01-25 | 2012-12-05 | Enanta Pharm Inc | Inhibidores del virus de la hepatitis c. |
| US8933110B2 (en) | 2010-01-25 | 2015-01-13 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| 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 |
| BR112012022311A2 (pt) | 2010-03-04 | 2016-08-23 | Enanta Pharm Inc | agentes farmacêuticos de combinação como inibidores da replicação de hcv. |
| 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 |
| US9127021B2 (en) | 2010-04-09 | 2015-09-08 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8778938B2 (en) | 2010-06-04 | 2014-07-15 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| NZ605440A (en) | 2010-06-10 | 2014-05-30 | Abbvie Bahamas Ltd | Solid compositions comprising an hcv inhibitor |
| ES2529119T3 (es) | 2010-07-02 | 2015-02-17 | Gilead Sciences, Inc. | Compuestos heterocíclicos condensados como moduladores de canales iónicos |
| WO2012003642A1 (en) * | 2010-07-09 | 2012-01-12 | Merck Sharp & Dohme Corp. | Fused tricyclic compounds and use thereof for treating viral diseases |
| JP2013541499A (ja) * | 2010-07-26 | 2013-11-14 | メルク・シャープ・エンド・ドーム・コーポレイション | 置換されたビフェニレン化合物およびウイルス性疾患の治療のためのその使用方法 |
| EP2603080A4 (en) | 2010-08-12 | 2014-01-22 | Enanta Pharm Inc | HEPATITIS C-VIRUS HEMMER |
| AU2011314168A1 (en) | 2010-09-29 | 2013-04-04 | Merck Sharp & Dohme Corp. | Fused tetracycle derivatives and methods of use thereof for the treatment of viral diseases |
| US8999967B2 (en) | 2010-09-29 | 2015-04-07 | Presidio Pharmaceuticals, Inc. | Tricyclic fused ring inhibitors of hepatitis C |
| NZ726475A (en) | 2010-11-17 | 2018-07-27 | Gilead Pharmasset Llc | Antiviral compounds |
| RU2452735C1 (ru) | 2010-11-30 | 2012-06-10 | Александр Васильевич Иващенко | Замещенные азолы, противовирусный активный компонент, фармацевтическая композиция, способ получения и применения |
| 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 |
| TWI510480B (zh) | 2011-05-10 | 2015-12-01 | Gilead Sciences Inc | 充當離子通道調節劑之稠合雜環化合物 |
| 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 |
| NO3175985T3 (enExample) | 2011-07-01 | 2018-04-28 | ||
| TWI549944B (zh) | 2011-07-01 | 2016-09-21 | 吉李德科學股份有限公司 | 作為離子通道調節劑之稠合雜環化合物 |
| EP2730572B1 (en) | 2011-07-09 | 2015-09-16 | Sunshine Lake Pharma Co., Ltd. | Spiro compounds as hepatitis c virus inhibitors |
| TW201321373A (zh) * | 2011-08-08 | 2013-06-01 | Glaxosmithkline Llc | 化合物 |
| WO2013030750A1 (en) | 2011-09-01 | 2013-03-07 | Lupin Limited | Antiviral compounds |
| EP2709613B2 (en) | 2011-09-16 | 2020-08-12 | Gilead Pharmasset LLC | Methods for treating hcv |
| UA110354C2 (uk) | 2011-11-16 | 2015-12-25 | Гайлід Фармассет Елелсі | Противірусні сполуки |
| 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 |
| CA2862755A1 (en) | 2012-02-10 | 2013-08-15 | Lupin Limited | Antiviral compounds with a dibenzooxaheterocycle moiety |
| US20130309196A1 (en) | 2012-05-16 | 2013-11-21 | Gilead Sciences, Inc. | Antiviral compounds |
| CN103420991B (zh) * | 2012-05-17 | 2017-07-07 | 乳源东阳光药业有限公司 | 作为丙型肝炎抑制剂的吡咯烷衍生物及其在药物中的应用 |
| 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 |
| 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 |
| 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 |
| 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 |
| UA118256C2 (uk) | 2013-01-31 | 2018-12-26 | Гіліад Фармассет Елелсі | Комбінований склад двох противірусних сполук |
| 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 |
| 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 |
| US9775831B2 (en) | 2013-07-17 | 2017-10-03 | 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 |
| WO2015103490A1 (en) | 2014-01-03 | 2015-07-09 | Abbvie, Inc. | Solid antiviral dosage forms |
| WO2015110048A1 (en) | 2014-01-23 | 2015-07-30 | Sunshine Lake Pharma Co., Ltd. | Bridged ring compounds as hepatitis c virus inhibitors, pharmaceutical compositions and uses thereof |
| 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 |
| US10617675B2 (en) | 2015-08-06 | 2020-04-14 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| ES2921855T3 (es) | 2016-04-07 | 2022-09-01 | Glaxosmithkline Ip Dev Ltd | Amidas heterocíclicas útiles como moduladores de proteínas |
| WO2017181383A1 (en) * | 2016-04-21 | 2017-10-26 | Merck Sharp & Dohme Corp. | Hepatitis c virus inhibitors |
| SI3752501T1 (sl) | 2018-02-13 | 2023-08-31 | Gilead Sciences, Inc. | Inhibitorji pd-1/pd-l1 |
| CA3093130C (en) | 2018-04-19 | 2023-10-17 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| SI3820572T1 (sl) | 2018-07-13 | 2023-12-29 | Gilead Sciences, Inc. | Inhibitorji pd-1/pd-l1 |
| JP7158577B2 (ja) | 2018-10-24 | 2022-10-21 | ギリアード サイエンシーズ， インコーポレイテッド | Ｐｄ－１／ｐｄ－ｌ１阻害剤 |
| KR20240012476A (ko) | 2021-05-21 | 2024-01-29 | 길리애드 사이언시즈, 인코포레이티드 | 지카 바이러스 저해제로서의 펜타사이클릭 유도체 |
| CR20230576A (es) | 2021-06-14 | 2024-04-05 | Scorpion Therapeutics Inc | Derivados de la urea que pueden ser utilizados para tratar el cáncer |
Family Cites Families (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL127610C (enExample) | 1965-06-23 | |||
| CH532608A (de) * | 1969-12-17 | 1973-01-15 | Ciba Geigy Ag | Verfahren zur Herstellung von Bis-aroxazolyl-Verbindungen |
| CH553807A (de) * | 1970-12-23 | 1974-09-13 | Sandoz Ag | Verfahren zur herstellung von dibenzthiophendioxidderivaten. |
| US3808206A (en) | 1971-06-29 | 1974-04-30 | Richardson Merrell Inc | Bis-basic ketones of phenoxathiins and antiviral compositions thereof |
| US4371690A (en) | 1979-07-12 | 1983-02-01 | E. I. Du Pont De Nemours And Company | Heat-resistant rigid polymers from difunctional 9,10-dihydro-9,10-ethanoanthracenes |
| US5288914A (en) | 1984-08-27 | 1994-02-22 | The Dow Chemical Company | Poly(arylcyclobutenes) |
| US5288924A (en) * | 1992-09-18 | 1994-02-22 | Mobil Oil Corporation | Process for starting up an olefin hydration reactor |
| US6054472A (en) | 1996-04-23 | 2000-04-25 | Vertex Pharmaceuticals, Incorporated | Inhibitors of IMPDH enzyme |
| US5807876A (en) | 1996-04-23 | 1998-09-15 | Vertex Pharmaceuticals Incorporated | Inhibitors of IMPDH enzyme |
| AU723730B2 (en) | 1996-04-23 | 2000-09-07 | Vertex Pharmaceuticals Incorporated | Urea derivatives as inhibitors of IMPDH enzyme |
| IN183120B (enExample) | 1996-10-18 | 1999-09-11 | Vertex Pharma | |
| GB9623908D0 (en) | 1996-11-18 | 1997-01-08 | Hoffmann La Roche | Amino acid derivatives |
| DE69816280T2 (de) | 1997-03-14 | 2004-05-27 | Vertex Pharmaceuticals Inc., Cambridge | Inhibitoren des impdh-enzyms |
| US6010848A (en) | 1997-07-02 | 2000-01-04 | Smithkline Beecham Corporation | Screening methods using an atpase protein from hepatitis C virus |
| PT1012180E (pt) | 1997-08-11 | 2005-04-29 | Boehringer Ingelheim Ca Ltd | Analogos de peptidos inibidores da hepatite c |
| CA2338490A1 (en) | 1998-07-27 | 2000-02-10 | Sergio Altamura | Diketoacid-derivatives as inhibitors of polymerases |
| US6323180B1 (en) | 1998-08-10 | 2001-11-27 | Boehringer Ingelheim (Canada) Ltd | Hepatitis C inhibitor tri-peptides |
| KR20010099623A (ko) | 1998-08-21 | 2001-11-09 | 비로파마 인코포레이티드 | 바이러스 감염 및 관련 질병을 치료 또는 예방하는화합물, 조성물 및 방법 |
| US6440985B1 (en) | 1998-09-04 | 2002-08-27 | Viropharma Incorporated | Methods for treating viral infections |
| AU751457B2 (en) | 1998-09-25 | 2002-08-15 | Viropharma Incorporated | Methods for treating or preventing viral infections and associated diseases |
| EE200100492A (et) | 1999-03-19 | 2002-12-16 | Vertex Pharmaceuticals Incorporated | Ensüümi IMPDH inhibiitorid |
| US6242602B1 (en) | 1999-03-29 | 2001-06-05 | Gentex Corporation | One pot synthesis of 5,10-dihydrophenazine compounds and 5,10-substituted dihydrophenazines |
| CA2389745C (en) | 1999-11-04 | 2010-03-23 | Shire Biochem Inc. | Method for the treatment or prevention of flaviviridae viral infection using nucleoside analogues |
| US20040034041A1 (en) | 2000-05-10 | 2004-02-19 | Dashyant Dhanak | Novel anti-infectives |
| 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 |
| JP2005500287A (ja) | 2001-06-11 | 2005-01-06 | シャイアー バイオケム インコーポレイテッド | Ｆｌａｖｉｖｉｒｕｓ感染の処置または予防のための化合物および方法 |
| PT1401825E (pt) | 2001-06-11 | 2009-10-23 | Virochem Pharma Inc | Compostos e métodos para o tratamento ou para a prevenção de infecções com flavivírus |
| 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 |
| JP2003212846A (ja) * | 2001-06-26 | 2003-07-30 | Japan Tobacco Inc | 縮合環化合物及びｃ型肝炎治療剤 |
| JP4558314B2 (ja) | 2001-07-20 | 2010-10-06 | ベーリンガー インゲルハイム （カナダ） リミテッド | ウイルスポリメラーゼインヒビター |
| EP2335700A1 (en) | 2001-07-25 | 2011-06-22 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis C virus polymerase inhibitors with a heterobicylic structure |
| CN101302182A (zh) * | 2001-07-25 | 2008-11-12 | 贝林格尔.英格海姆加拿大有限公司 | 病毒聚合酶抑制剂 |
| US20050009873A1 (en) | 2001-11-02 | 2005-01-13 | Gianpaolo Bravi | Acyl dihydro pyrrole derivatives as hcv inhibitors |
| JP2005511573A (ja) | 2001-11-02 | 2005-04-28 | グラクソ グループ リミテッド | Ｈｃｖ阻害剤としての４−（５−員）−ヘテロアリールアシルピロリジン誘導体 |
| JP2005515172A (ja) | 2001-11-02 | 2005-05-26 | グラクソ グループ リミテッド | Ｈｃｖ阻害剤としての４−（６−員）−ヘテロアリールアシルピロリジン誘導体 |
| UA84050C2 (en) | 2004-01-30 | 2008-09-10 | Медивир Аб | Hcv ns-3-serine protease inhibitors |
| WO2006039356A2 (en) | 2004-09-29 | 2006-04-13 | Cytovia, Inc. | Substituted n-aryl-9-oxo-9h-fluorene-1-carboxamides and analogs as activators of caspases and inducers of apoptosis |
| WO2006050496A1 (en) * | 2004-11-02 | 2006-05-11 | E.I. Dupont De Nemours And Company | Substituted anthracenes and electronic devices containing the substituted anthracenes |
| DE102005022020A1 (de) * | 2005-05-12 | 2006-11-23 | Merckle Gmbh | Dibenzocycloheptanverbindungen und pharmazeutische Mittel, welche diese Verbindungen enthalten |
| US8143288B2 (en) | 2005-06-06 | 2012-03-27 | Bristol-Myers Squibb Company | Inhibitors of HCV replication |
| 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 |
| 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 |
| US7741347B2 (en) * | 2007-05-17 | 2010-06-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| 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 |
| US7704992B2 (en) * | 2008-02-13 | 2010-04-27 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| JP5266786B2 (ja) * | 2008-02-20 | 2013-08-21 | 富士ゼロックス株式会社 | 新規なフェノチアジン化合物 |
| WO2010096462A1 (en) * | 2009-02-17 | 2010-08-26 | Enanta Pharmaceuticals, Inc | Linked diimidazole derivatives |
| AU2010229795A1 (en) | 2009-03-27 | 2011-10-13 | Presidio Pharmaceuticals, Inc. | Fused ring inhibitors of hepatitis C |
-
2010
- 2010-03-25 AU AU2010229795A patent/AU2010229795A1/en not_active Abandoned
- 2010-03-25 WO PCT/US2010/028730 patent/WO2010111534A1/en not_active Ceased
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- 2010-03-25 KR KR1020117025221A patent/KR20110131312A/ko not_active Withdrawn
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- 2010-03-25 JP JP2012502264A patent/JP5735482B2/ja not_active Expired - Fee Related
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| BRPI1012282A2 (pt) | 2015-09-22 |
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| IL215202A0 (en) | 2011-12-29 |
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| AR076164A1 (es) | 2011-05-26 |
| CN102427726B (zh) | 2014-10-08 |
| EP2410843A4 (en) | 2012-08-08 |
| CA2755658A1 (en) | 2010-09-30 |
| CN102427726A (zh) | 2012-04-25 |
| US9150554B2 (en) | 2015-10-06 |
| ZA201107753B (en) | 2012-07-25 |
| CL2011002377A1 (es) | 2012-01-20 |
| CO6450600A2 (es) | 2012-05-31 |
| KR20110131312A (ko) | 2011-12-06 |
| TW201038560A (en) | 2010-11-01 |
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