ZA200408243B - Inhibitors of serine proteases, particularly hepatitus C virus NS3-NS4 protease - Google Patents
Inhibitors of serine proteases, particularly hepatitus C virus NS3-NS4 protease Download PDFInfo
- Publication number
- ZA200408243B ZA200408243B ZA200408243A ZA200408243A ZA200408243B ZA 200408243 B ZA200408243 B ZA 200408243B ZA 200408243 A ZA200408243 A ZA 200408243A ZA 200408243 A ZA200408243 A ZA 200408243A ZA 200408243 B ZA200408243 B ZA 200408243B
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- South Africa
- Prior art keywords
- aliphatic
- compound according
- independently
- cycloalkyl
- aryl
- Prior art date
Links
- 102000012479 Serine Proteases Human genes 0.000 title claims description 12
- 108010022999 Serine Proteases Proteins 0.000 title claims description 12
- 239000003112 inhibitor Substances 0.000 title claims description 11
- 108091005804 Peptidases Proteins 0.000 title claims description 9
- 239000004365 Protease Substances 0.000 title claims description 8
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 title claims 4
- 241000700605 Viruses Species 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 79
- 229910052757 nitrogen Inorganic materials 0.000 claims description 45
- 125000000623 heterocyclic group Chemical group 0.000 claims description 41
- 125000001424 substituent group Chemical group 0.000 claims description 41
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 37
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 125000005842 heteroatom Chemical group 0.000 claims description 34
- 125000001931 aliphatic group Chemical group 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 22
- 125000006717 (C3-C10) cycloalkenyl group Chemical group 0.000 claims description 20
- 125000006714 (C3-C10) heterocyclyl group Chemical group 0.000 claims description 20
- -1 1,2-methylenedioxy Chemical group 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 8
- 239000003443 antiviral agent Substances 0.000 claims description 7
- 208000015181 infectious disease Diseases 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 229940079322 interferon Drugs 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims 26
- 125000000217 alkyl group Chemical group 0.000 claims 14
- 125000004429 atom Chemical group 0.000 claims 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 10
- 125000000165 tricyclic carbocycle group Chemical group 0.000 claims 7
- 229910052799 carbon Inorganic materials 0.000 claims 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 5
- 125000004043 oxo group Chemical group O=* 0.000 claims 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims 4
- 229910052796 boron Inorganic materials 0.000 claims 4
- 125000004432 carbon atom Chemical group C* 0.000 claims 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
- 230000002519 immonomodulatory effect Effects 0.000 claims 4
- 125000003396 thiol group Chemical group [H]S* 0.000 claims 4
- 125000000464 thioxo group Chemical group S=* 0.000 claims 4
- 239000008280 blood Substances 0.000 claims 3
- 210000004369 blood Anatomy 0.000 claims 3
- 210000001124 body fluid Anatomy 0.000 claims 3
- 125000002837 carbocyclic group Chemical group 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
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- 125000006721 (C5-C10) heteroaryl (C1-C6) alkyl group Chemical group 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- 102000005741 Metalloproteases Human genes 0.000 claims 2
- 108010006035 Metalloproteases Proteins 0.000 claims 2
- 108060004795 Methyltransferase Proteins 0.000 claims 2
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical group 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 2
- 102000007501 Thymosin Human genes 0.000 claims 2
- 108010046075 Thymosin Proteins 0.000 claims 2
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims 2
- 229960003805 amantadine Drugs 0.000 claims 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims 2
- 239000012472 biological sample Substances 0.000 claims 2
- 239000010839 body fluid Substances 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 125000006574 non-aromatic ring group Chemical group 0.000 claims 2
- 229960000329 ribavirin Drugs 0.000 claims 2
- IQFYYKKMVGJFEH-CSMHCCOUSA-N telbivudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1O[C@@H](CO)[C@H](O)C1 IQFYYKKMVGJFEH-CSMHCCOUSA-N 0.000 claims 2
- 229960005311 telbivudine Drugs 0.000 claims 2
- LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=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(C)C)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(C)C)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)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 claims 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
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- 101100102516 Clonostachys rogersoniana vern gene Proteins 0.000 claims 1
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- 101100136092 Drosophila melanogaster peng gene Proteins 0.000 claims 1
- 101100460719 Mus musculus Noto gene Proteins 0.000 claims 1
- 101150049354 Scgb1a1 gene Proteins 0.000 claims 1
- 101800001838 Serine protease/helicase NS3 Proteins 0.000 claims 1
- 101100187345 Xenopus laevis noto gene Proteins 0.000 claims 1
- 239000008186 active pharmaceutical agent Substances 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 108010091987 aposome Proteins 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims 1
- 238000011109 contamination Methods 0.000 claims 1
- 125000005356 cycloalkylalkenyl group Chemical group 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 1
- 125000002950 monocyclic group Chemical group 0.000 claims 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
- 239000000651 prodrug Substances 0.000 claims 1
- 229940002612 prodrug Drugs 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 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 1
- 150000003839 salts Chemical class 0.000 claims 1
- 239000000523 sample Substances 0.000 claims 1
- 239000011232 storage material Substances 0.000 claims 1
- 241000711549 Hepacivirus C Species 0.000 description 11
- 208000005176 Hepatitis C Diseases 0.000 description 6
- 108010076039 Polyproteins Proteins 0.000 description 6
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- 231100000283 hepatitis Toxicity 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 4
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- 235000019419 proteases Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
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- 230000007017 scission Effects 0.000 description 4
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- 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
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- 238000011282 treatment Methods 0.000 description 3
- 230000029812 viral genome replication Effects 0.000 description 3
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- 150000001413 amino acids Chemical class 0.000 description 2
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- 230000008520 organization Effects 0.000 description 2
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- 101800000515 Non-structural protein 3 Proteins 0.000 description 1
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- 208000037581 Persistent Infection Diseases 0.000 description 1
- 241000710772 Yellow fever virus Species 0.000 description 1
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- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
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- 238000012512 characterization method Methods 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
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- 230000007423 decrease Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
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- 238000010369 molecular cloning Methods 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
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- 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
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
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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
- C07D401/02—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 two hetero rings
- C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
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- 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
- C07D403/02—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 two hetero rings
- C07D403/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
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- 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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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
- C07D417/02—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 two hetero rings
- C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
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- 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
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
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- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
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- 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
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- 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
- C07K5/10—Tetrapeptides
- C07K5/1024—Tetrapeptides with the first amino acid being heterocyclic
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- 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
- C07K5/10—Tetrapeptides
- C07K5/1027—Tetrapeptides containing heteroatoms different from O, S, or N
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- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
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- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
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ZA200408243A ZA200408243B (en) | 2002-04-11 | 2004-10-12 | Inhibitors of serine proteases, particularly hepatitus C virus NS3-NS4 protease |
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WO2002022828A1 (en) * | 2000-09-12 | 2002-03-21 | Degussa Ag | Isolation and sequencing of the pknb gene of c. glutamicum |
US6846806B2 (en) * | 2000-10-23 | 2005-01-25 | Bristol-Myers Squibb Company | Peptide inhibitors of Hepatitis C virus NS3 protein |
WO2002060926A2 (en) | 2000-11-20 | 2002-08-08 | Bristol-Myers Squibb Company | Hepatitis c tripeptide inhibitors |
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WO2002048116A2 (en) | 2000-12-13 | 2002-06-20 | Bristol-Myers Squibb Pharma Company | Inhibitors of hepatitis c virus ns3 protease |
GB0107924D0 (en) | 2001-03-29 | 2001-05-23 | Angeletti P Ist Richerche Bio | Inhibitor of hepatitis C virus NS3 protease |
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JP2005535574A (ja) * | 2002-04-11 | 2005-11-24 | 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 | セリンプロテアーゼ、特にhcvns3−ns4aプロテアーゼのインヒビター |
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WO2004092161A1 (en) * | 2003-04-11 | 2004-10-28 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hcv ns3-ns4a protease |
UY28423A1 (es) * | 2003-07-18 | 2005-02-28 | Vertex Pharma | Inhibidores de proteasas serinas, en especial proteasa ns3-ns4a del vhc.- |
EP2311851A3 (en) * | 2004-02-04 | 2011-05-25 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly HCV NS3-NS4A protease |
-
2003
- 2003-04-11 JP JP2003584048A patent/JP2005535574A/ja active Pending
- 2003-04-11 KR KR10-2004-7016168A patent/KR20040099425A/ko not_active Application Discontinuation
- 2003-04-11 SG SG200700139-9A patent/SG159385A1/en unknown
- 2003-04-11 KR KR1020117004808A patent/KR20110028665A/ko not_active Application Discontinuation
- 2003-04-11 PL PL03373399A patent/PL373399A1/xx not_active Application Discontinuation
- 2003-04-11 NZ NZ561851A patent/NZ561851A/en not_active IP Right Cessation
- 2003-04-11 CN CNB03809665XA patent/CN100381440C/zh not_active Expired - Fee Related
- 2003-04-11 EP EP12160782A patent/EP2468744A2/en not_active Withdrawn
- 2003-04-11 EP EP03719741A patent/EP1497282A2/en not_active Withdrawn
- 2003-04-11 NZ NZ575692A patent/NZ575692A/en not_active IP Right Cessation
- 2003-04-11 AU AU2003223602A patent/AU2003223602B8/en not_active Ceased
- 2003-04-11 US US10/412,600 patent/US7273885B2/en not_active Expired - Fee Related
- 2003-04-11 MX MXPA04009938A patent/MXPA04009938A/es active IP Right Grant
- 2003-04-11 CN CNA2008100823499A patent/CN101245097A/zh active Pending
- 2003-04-11 CA CA2481369A patent/CA2481369C/en not_active Expired - Fee Related
- 2003-04-11 RU RU2004133044/04A patent/RU2004133044A/ru not_active Application Discontinuation
- 2003-04-11 TW TW092108412A patent/TW200403236A/zh unknown
- 2003-04-11 WO PCT/US2003/011459 patent/WO2003087092A2/en active Application Filing
-
2004
- 2004-10-10 IL IL16445504A patent/IL164455A0/xx unknown
- 2004-10-12 ZA ZA200408243A patent/ZA200408243B/en unknown
- 2004-11-10 NO NO20044889A patent/NO20044889L/no unknown
-
2006
- 2006-01-27 HK HK06101291A patent/HK1081196A1/xx not_active IP Right Cessation
-
2007
- 2007-07-23 US US11/880,629 patent/US20070292933A1/en not_active Abandoned
-
2009
- 2009-05-28 JP JP2009128587A patent/JP2009185081A/ja active Pending
- 2009-06-03 US US12/477,581 patent/US20100173851A1/en not_active Abandoned
- 2009-10-30 AU AU2009233604A patent/AU2009233604A1/en not_active Abandoned
-
2010
- 2010-07-01 JP JP2010151000A patent/JP2010241821A/ja active Pending
-
2011
- 2011-05-26 NO NO20110773A patent/NO20110773L/no unknown
Also Published As
Publication number | Publication date |
---|---|
WO2003087092A3 (en) | 2004-09-10 |
KR20110028665A (ko) | 2011-03-21 |
JP2010241821A (ja) | 2010-10-28 |
EP2468744A2 (en) | 2012-06-27 |
CA2481369C (en) | 2012-07-10 |
MXPA04009938A (es) | 2004-12-13 |
KR20040099425A (ko) | 2004-11-26 |
AU2009233604A1 (en) | 2009-11-26 |
TW200403236A (en) | 2004-03-01 |
HK1081196A1 (en) | 2006-05-12 |
US20100173851A1 (en) | 2010-07-08 |
US20070292933A1 (en) | 2007-12-20 |
EP1497282A2 (en) | 2005-01-19 |
CN1649864A (zh) | 2005-08-03 |
US20040018986A1 (en) | 2004-01-29 |
PL373399A1 (en) | 2005-08-22 |
NZ561851A (en) | 2009-05-31 |
CN101245097A (zh) | 2008-08-20 |
CA2481369A1 (en) | 2003-10-23 |
NZ575692A (en) | 2009-10-30 |
AU2003223602B2 (en) | 2010-05-13 |
RU2004133044A (ru) | 2006-01-27 |
WO2003087092A2 (en) | 2003-10-23 |
NO20044889L (no) | 2005-01-10 |
AU2003223602B8 (en) | 2010-05-27 |
JP2005535574A (ja) | 2005-11-24 |
JP2009185081A (ja) | 2009-08-20 |
CN100381440C (zh) | 2008-04-16 |
IL164455A0 (en) | 2005-12-18 |
NO20110773L (no) | 2005-01-10 |
SG159385A1 (en) | 2010-03-30 |
AU2003223602A1 (en) | 2003-10-27 |
US7273885B2 (en) | 2007-09-25 |
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