ES2381308T3 - Inhibidores del virus de la hepatitis C - Google Patents
Inhibidores del virus de la hepatitis C Download PDFInfo
- Publication number
- ES2381308T3 ES2381308T3 ES07864446T ES07864446T ES2381308T3 ES 2381308 T3 ES2381308 T3 ES 2381308T3 ES 07864446 T ES07864446 T ES 07864446T ES 07864446 T ES07864446 T ES 07864446T ES 2381308 T3 ES2381308 T3 ES 2381308T3
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- Prior art keywords
- alkyl
- cycloalkyl
- compound
- hcv
- mmol
- 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.)
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- 239000003112 inhibitor Substances 0.000 title claims abstract description 23
- 241000711549 Hepacivirus C Species 0.000 title abstract description 89
- 150000001875 compounds Chemical class 0.000 claims abstract description 256
- 239000000203 mixture Substances 0.000 claims abstract description 142
- 125000000217 alkyl group Chemical group 0.000 claims description 141
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 76
- 125000000623 heterocyclic group Chemical group 0.000 claims description 62
- 125000003118 aryl group Chemical group 0.000 claims description 55
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 52
- 150000003839 salts Chemical class 0.000 claims description 46
- 125000001188 haloalkyl group Chemical group 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 35
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 35
- 230000000694 effects Effects 0.000 claims description 29
- 229910003827 NRaRb Inorganic materials 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- 102000014150 Interferons Human genes 0.000 claims description 24
- 108010050904 Interferons Proteins 0.000 claims description 24
- 125000003342 alkenyl group Chemical group 0.000 claims description 24
- 229940079322 interferon Drugs 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 24
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 21
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 21
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 20
- 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 19
- 229960000329 ribavirin Drugs 0.000 claims description 19
- 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 19
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 15
- 125000004994 halo alkoxy alkyl group Chemical group 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 108010047761 Interferon-alpha Proteins 0.000 claims description 12
- 102000006992 Interferon-alpha Human genes 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 11
- 208000015181 infectious disease Diseases 0.000 claims description 11
- 229910052702 rhenium Inorganic materials 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
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- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 9
- 125000005170 cycloalkyloxycarbonyl group Chemical group 0.000 claims description 9
- 125000004993 haloalkoxycarbonyl group Chemical group 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 125000002950 monocyclic group Chemical group 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- 101800001019 Non-structural protein 4B Proteins 0.000 claims description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
- 229910052701 rubidium Inorganic materials 0.000 claims description 7
- 101710200424 Inosine-5'-monophosphate dehydrogenase Proteins 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 6
- 229910052717 sulfur Chemical group 0.000 claims description 6
- 108060004795 Methyltransferase Proteins 0.000 claims description 5
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- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 125000005243 carbonyl alkyl group Chemical group 0.000 claims description 5
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 5
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 5
- 238000011161 development Methods 0.000 claims description 5
- 125000004692 haloalkylcarbonyl group Chemical group 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Chemical group 0.000 claims description 5
- 229910052703 rhodium Inorganic materials 0.000 claims description 5
- 239000011593 sulfur 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
- 102100040018 Interferon alpha-2 Human genes 0.000 claims description 4
- 108010079944 Interferon-alpha2b Proteins 0.000 claims description 4
- 102000013462 Interleukin-12 Human genes 0.000 claims description 4
- 108010065805 Interleukin-12 Proteins 0.000 claims description 4
- 102000000588 Interleukin-2 Human genes 0.000 claims description 4
- 108010002350 Interleukin-2 Proteins 0.000 claims description 4
- 102000004889 Interleukin-6 Human genes 0.000 claims description 4
- 108090001005 Interleukin-6 Proteins 0.000 claims description 4
- 108010006035 Metalloproteases Proteins 0.000 claims description 4
- 102000005741 Metalloproteases Human genes 0.000 claims description 4
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 4
- 229960003805 amantadine Drugs 0.000 claims description 4
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 claims description 4
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- 108700027921 interferon tau Proteins 0.000 claims description 4
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- 230000004044 response Effects 0.000 claims description 4
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- 108020005544 Antisense RNA Proteins 0.000 claims description 3
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- 239000002348 inosinate dehydrogenase inhibitor Substances 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 153
- 239000000243 solution Substances 0.000 description 162
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- 238000002360 preparation method Methods 0.000 description 151
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 135
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- 239000000047 product Substances 0.000 description 113
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 107
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 96
- 238000005160 1H NMR spectroscopy Methods 0.000 description 86
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 84
- -1 bicyclo [3,1,1] heptyl Chemical group 0.000 description 81
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
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- 101710144111 Non-structural protein 3 Proteins 0.000 description 31
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- 230000015572 biosynthetic process Effects 0.000 description 27
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
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- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
-
- 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
-
- 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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- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Peptides Or Proteins (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US939780 | 1992-09-03 | ||
| US86613006P | 2006-11-16 | 2006-11-16 | |
| US866130P | 2006-11-16 | ||
| US11/939,780 US7888464B2 (en) | 2006-11-16 | 2007-11-14 | Hepatitis C virus inhibitors |
| PCT/US2007/084799 WO2008064066A1 (en) | 2006-11-16 | 2007-11-15 | Hepatitis c virus inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2381308T3 true ES2381308T3 (es) | 2012-05-25 |
Family
ID=39247306
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES07864446T Active ES2381308T3 (es) | 2006-11-16 | 2007-11-15 | Inhibidores del virus de la hepatitis C |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US7888464B2 (OSRAM) |
| EP (1) | EP2086995B1 (OSRAM) |
| JP (1) | JP5241729B2 (OSRAM) |
| KR (1) | KR20090083462A (OSRAM) |
| AT (1) | ATE546460T1 (OSRAM) |
| AU (1) | AU2007323793A1 (OSRAM) |
| BR (1) | BRPI0719008A2 (OSRAM) |
| CA (1) | CA2669856A1 (OSRAM) |
| CO (1) | CO6190510A2 (OSRAM) |
| EA (1) | EA015827B1 (OSRAM) |
| ES (1) | ES2381308T3 (OSRAM) |
| IL (1) | IL198741A0 (OSRAM) |
| MX (1) | MX2009004943A (OSRAM) |
| NO (1) | NO20091871L (OSRAM) |
| NZ (1) | NZ576814A (OSRAM) |
| WO (1) | WO2008064066A1 (OSRAM) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY140680A (en) | 2002-05-20 | 2010-01-15 | Bristol Myers Squibb Co | Hepatitis c virus inhibitors |
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- 2007-11-15 EA EA200900697A patent/EA015827B1/ru not_active IP Right Cessation
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| NZ576814A (en) | 2011-06-30 |
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| BRPI0719008A2 (pt) | 2013-12-03 |
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| AU2007323793A1 (en) | 2008-05-29 |
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| CO6190510A2 (es) | 2010-08-19 |
| EA200900697A1 (ru) | 2010-02-26 |
| EP2086995B1 (en) | 2012-02-22 |
| US7888464B2 (en) | 2011-02-15 |
| NO20091871L (no) | 2009-07-31 |
| KR20090083462A (ko) | 2009-08-03 |
| IL198741A0 (en) | 2010-02-17 |
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