AU2009322393B2 - Inhibitors of HCV NS5A - Google Patents
Inhibitors of HCV NS5A Download PDFInfo
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- AU2009322393B2 AU2009322393B2 AU2009322393A AU2009322393A AU2009322393B2 AU 2009322393 B2 AU2009322393 B2 AU 2009322393B2 AU 2009322393 A AU2009322393 A AU 2009322393A AU 2009322393 A AU2009322393 A AU 2009322393A AU 2009322393 B2 AU2009322393 B2 AU 2009322393B2
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- 239000003112 inhibitor Substances 0.000 title description 24
- 101800001014 Non-structural protein 5A Proteins 0.000 title description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 445
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 208000005176 Hepatitis C Diseases 0.000 claims abstract description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 152
- 125000003118 aryl group Chemical group 0.000 claims description 130
- 125000001072 heteroaryl group Chemical group 0.000 claims description 130
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 115
- 150000003839 salts Chemical class 0.000 claims description 107
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 100
- 239000001257 hydrogen Substances 0.000 claims description 89
- 229910052739 hydrogen Inorganic materials 0.000 claims description 89
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 86
- 125000000217 alkyl group Chemical group 0.000 claims description 84
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 82
- 125000001589 carboacyl group Chemical group 0.000 claims description 82
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 81
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 78
- 150000002431 hydrogen Chemical class 0.000 claims description 68
- 229910052757 nitrogen Inorganic materials 0.000 claims description 50
- 229910052799 carbon Inorganic materials 0.000 claims description 41
- 125000003545 alkoxy group Chemical group 0.000 claims description 36
- 229940124530 sulfonamide Drugs 0.000 claims description 35
- 150000003456 sulfonamides Chemical class 0.000 claims description 35
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 35
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- -1 -OH Chemical group 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 150000002367 halogens Chemical class 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
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- WDPVNDRNBJNETA-JBLDHEPKSA-N (2s)-2-amino-6-[[(2s)-1-[[(1r)-1-carboxy-2-methylpropyl]amino]-1-oxo-4-sulfanylbutan-2-yl]amino]-6-oxohexanoic acid Chemical compound CC(C)[C@H](C(O)=O)NC(=O)[C@H](CCS)NC(=O)CCC[C@H](N)C(O)=O WDPVNDRNBJNETA-JBLDHEPKSA-N 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
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- 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 33
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- 125000004093 cyano group Chemical group *C#N 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 24
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- 229910052702 rhenium Inorganic materials 0.000 description 22
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- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 20
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 17
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 239000000284 extract Substances 0.000 description 16
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- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 14
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
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Classifications
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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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
- 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
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
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- Communicable Diseases (AREA)
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- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
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| US11972308P | 2008-12-03 | 2008-12-03 | |
| US61/119,723 | 2008-12-03 | ||
| US17359009P | 2009-04-28 | 2009-04-28 | |
| US21488109P | 2009-04-28 | 2009-04-28 | |
| US61/214,881 | 2009-04-28 | ||
| US61/173,590 | 2009-04-28 | ||
| US18295809P | 2009-06-01 | 2009-06-01 | |
| US18295209P | 2009-06-01 | 2009-06-01 | |
| US61/182,958 | 2009-06-01 | ||
| US61/182,952 | 2009-06-01 | ||
| PCT/US2009/066459 WO2010065674A1 (en) | 2008-12-03 | 2009-12-02 | Inhibitors of hcv ns5a |
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| AU2009322393A1 AU2009322393A1 (en) | 2011-07-07 |
| AU2009322393B2 true AU2009322393B2 (en) | 2017-02-02 |
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| AU2009322393A Ceased AU2009322393B2 (en) | 2008-12-03 | 2009-12-02 | Inhibitors of HCV NS5A |
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| EP (2) | EP2682393A1 (enExample) |
| JP (1) | JP5762971B2 (enExample) |
| KR (1) | KR101784830B1 (enExample) |
| CN (2) | CN104163816A (enExample) |
| AR (1) | AR080263A1 (enExample) |
| AU (1) | AU2009322393B2 (enExample) |
| BR (1) | BRPI0922366B8 (enExample) |
| CA (1) | CA2746004C (enExample) |
| CL (1) | CL2011001333A1 (enExample) |
| CO (1) | CO6390077A2 (enExample) |
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