UA73480C2 - Hepatitis c virus peptide inhibitors, a method for the preparation thereof and pharmaceutical composition - Google Patents
Hepatitis c virus peptide inhibitors, a method for the preparation thereof and pharmaceutical composition Download PDFInfo
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- UA73480C2 UA73480C2 UA2001031604A UA2001031604A UA73480C2 UA 73480 C2 UA73480 C2 UA 73480C2 UA 2001031604 A UA2001031604 A UA 2001031604A UA 2001031604 A UA2001031604 A UA 2001031604A UA 73480 C2 UA73480 C2 UA 73480C2
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- 239000011630 iodine Chemical group 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
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- 238000001698 laser desorption ionisation Methods 0.000 description 1
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- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
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- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000006225 natural substrate Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- ZHCAAFJSYLFLPX-UHFFFAOYSA-N nitrocyclohexatriene Chemical group [O-][N+](=O)C1=CC=C=C[CH]1 ZHCAAFJSYLFLPX-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
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- 229940127073 nucleoside analogue Drugs 0.000 description 1
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- 230000003647 oxidation Effects 0.000 description 1
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- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
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- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical group CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
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- 229940043230 sarcosine Drugs 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- SETMGIIITGNLAS-UHFFFAOYSA-N spizofurone Chemical compound O=C1C2=CC(C(=O)C)=CC=C2OC21CC2 SETMGIIITGNLAS-UHFFFAOYSA-N 0.000 description 1
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
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- 230000035897 transcription Effects 0.000 description 1
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000005310 triazolidinyl group Chemical class N1(NNCC1)* 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-O triphenylphosphanium Chemical compound C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-O 0.000 description 1
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- 238000005199 ultracentrifugation Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
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- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
-
- 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
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Biophysics (AREA)
- Diabetes (AREA)
- Gastroenterology & Hepatology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US9594598P | 1998-08-10 | 1998-08-10 | |
PCT/CA1999/000737 WO2000009558A1 (fr) | 1998-08-10 | 1999-08-09 | Peptides inhibiteurs de l'hepatite c |
Publications (1)
Publication Number | Publication Date |
---|---|
UA73480C2 true UA73480C2 (en) | 2005-08-15 |
Family
ID=22254308
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
UA2001031604A UA73480C2 (en) | 1998-08-10 | 1999-09-08 | Hepatitis c virus peptide inhibitors, a method for the preparation thereof and pharmaceutical composition |
Country Status (33)
Country | Link |
---|---|
EP (1) | EP1105422B1 (fr) |
JP (1) | JP4435982B2 (fr) |
KR (1) | KR100629791B1 (fr) |
CN (1) | CN1166690C (fr) |
AR (1) | AR022061A1 (fr) |
AT (1) | ATE317854T1 (fr) |
AU (1) | AU764655B2 (fr) |
BG (1) | BG64956B1 (fr) |
BR (1) | BR9912943A (fr) |
CA (1) | CA2336597C (fr) |
CO (1) | CO5180537A1 (fr) |
CZ (1) | CZ301405B6 (fr) |
DE (1) | DE69929887T2 (fr) |
DK (1) | DK1105422T3 (fr) |
EA (1) | EA004765B1 (fr) |
EE (1) | EE200100080A (fr) |
ES (1) | ES2257066T3 (fr) |
HK (1) | HK1039947B (fr) |
HR (1) | HRP20010101A2 (fr) |
HU (1) | HUP0104548A3 (fr) |
ID (1) | ID27784A (fr) |
IL (2) | IL141011A0 (fr) |
MY (1) | MY125014A (fr) |
NO (1) | NO20010604D0 (fr) |
NZ (1) | NZ510395A (fr) |
PL (1) | PL199419B1 (fr) |
RS (1) | RS49819B (fr) |
SK (1) | SK286846B6 (fr) |
TR (1) | TR200100438T2 (fr) |
TW (1) | TW577895B (fr) |
UA (1) | UA73480C2 (fr) |
WO (1) | WO2000009558A1 (fr) |
ZA (1) | ZA200100972B (fr) |
Families Citing this family (153)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR022061A1 (es) * | 1998-08-10 | 2002-09-04 | Boehringer Ingelheim Ca Ltd | Peptidos inhibidores de la hepatitis c, una composicion farmaceutica que los contiene, el uso de los mismos para preparar una composicion farmaceutica, el uso de un producto intermedio para la preparacion de estos peptidos y un procedimiento para la preparacion de un peptido analogo de los mismos. |
US6608027B1 (en) | 1999-04-06 | 2003-08-19 | Boehringer Ingelheim (Canada) Ltd | Macrocyclic peptides active against the hepatitis C virus |
UA74546C2 (en) * | 1999-04-06 | 2006-01-16 | Boehringer Ingelheim Ca Ltd | Macrocyclic peptides having activity relative to hepatitis c virus, a pharmaceutical composition and use of the pharmaceutical composition |
MXPA02009920A (es) * | 2000-04-05 | 2003-03-27 | Schering Corp | Inhibidores macrociclicos de la ns3-serina proteasa, del virus de la hepatitis c9 que comprenden partes p2 n-ciclicas. |
HUP0302957A2 (hu) | 2000-04-19 | 2003-12-29 | Schering Corporation | Hepatitis C vírus alkil- és aril-alanin P2 csoportokat tartalmazó makrociklusos NS-3 szerin proteáz inhibitorai |
CZ2003195A3 (cs) | 2000-07-21 | 2003-04-16 | Schering Corporation | Peptidové inhibitory serinové proteázy NS3 a farmaceutický prostředek |
AR029851A1 (es) | 2000-07-21 | 2003-07-16 | Dendreon Corp | Nuevos peptidos como inhibidores de ns3-serina proteasa del virus de hepatitis c |
BR0112540A (pt) | 2000-07-21 | 2003-06-24 | Schering Corp | Peptìdios como inibidores da ns-3-serina protease do vìrus da hepatite c |
SV2003000617A (es) | 2000-08-31 | 2003-01-13 | Lilly Co Eli | Inhibidores de la proteasa peptidomimetica ref. x-14912m |
US6846806B2 (en) | 2000-10-23 | 2005-01-25 | Bristol-Myers Squibb Company | Peptide inhibitors of Hepatitis C virus NS3 protein |
ES2324594T3 (es) | 2000-12-12 | 2009-08-11 | Schering Corporation | Diaril peptidicos utilizados como inhibidores de la serina proteasa ns3 del virus de la hepatitis c. |
JP4455056B2 (ja) * | 2001-07-11 | 2010-04-21 | 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 | 架橋二環式セリンプロテアーゼ阻害剤 |
AU2002348414B2 (en) * | 2001-10-24 | 2009-10-01 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine protease, particularly hepatitis C virus NS3-NS4A protease, incorporating a fused ring system |
PE20030857A1 (es) | 2002-01-23 | 2003-10-25 | Schering Corp | Compuestos como inhibidores de la proteasa serina ns3 del virus de la hepatitis c |
US7119072B2 (en) | 2002-01-30 | 2006-10-10 | Boehringer Ingelheim (Canada) Ltd. | Macrocyclic peptides active against the hepatitis C virus |
US6642204B2 (en) | 2002-02-01 | 2003-11-04 | Boehringer Ingelheim International Gmbh | Hepatitis C inhibitor tri-peptides |
US7091184B2 (en) | 2002-02-01 | 2006-08-15 | Boehringer Ingelheim International Gmbh | Hepatitis C inhibitor tri-peptides |
PL373399A1 (en) | 2002-04-11 | 2005-08-22 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hcv ns3-ns4a protease |
PL211889B1 (pl) | 2002-05-20 | 2012-07-31 | Bristol Myers Squibb Co | Pochodna heterocyklosulfonamidowa, kompozycja ją zawierająca oraz ich zastosowanie |
ATE413411T1 (de) | 2002-05-20 | 2008-11-15 | Bristol Myers Squibb Co | Substituierte cycloalkyl p1' hepatitis c virus inhibitoren |
WO2004032827A2 (fr) | 2002-05-20 | 2004-04-22 | Bristol-Myers Squibb Company | Inhibiteurs du virus de l'hepatite c |
MY140680A (en) | 2002-05-20 | 2010-01-15 | Bristol Myers Squibb Co | Hepatitis c virus inhibitors |
US20050075279A1 (en) | 2002-10-25 | 2005-04-07 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis C virus |
WO2004101605A1 (fr) * | 2003-03-05 | 2004-11-25 | Boehringer Ingelheim International Gmbh | Composes d'inhibition de l'hepatite c |
WO2004101602A2 (fr) | 2003-03-05 | 2004-11-25 | Boehringer Ingelheim International Gmbh | Analogues de peptides inhibiteurs de l'hepatite c |
KR100971347B1 (ko) * | 2003-03-08 | 2010-07-20 | 주식회사유한양행 | 씨형 간염바이러스 감염 치료용 엔에스3 프로테아제 억제제 |
EP1615947A2 (fr) | 2003-04-10 | 2006-01-18 | Boehringer Ingelheim International GmbH | Procede de preparation de composes macrocycliques |
US7176208B2 (en) | 2003-04-18 | 2007-02-13 | Enanta Pharmaceuticals, Inc. | Quinoxalinyl macrocyclic hepatitis C serine protease inhibitors |
CL2004001161A1 (es) | 2003-05-21 | 2005-04-08 | Boehringer Ingelheim Int | Compuestos describe compuestos derivados de quinolina; composicion farmaceutica; y su uso para tratar una enfermedad causada por el virus de la hepatitis c. |
EP1664090A2 (fr) | 2003-08-26 | 2006-06-07 | Schering Corporation | Nouveaux inhibiteurs peptidomimetiques de la serine protease ns3 du virus de l'hepatite c |
TWI359147B (en) | 2003-09-05 | 2012-03-01 | Vertex Pharma | Inhibitors of serine proteases, particularly hcv n |
UY28525A1 (es) | 2003-09-22 | 2005-04-29 | Boehringer Ingelheim Int | Péptidos macrociclicos activos contra en virus de la hepatitis c |
AR046166A1 (es) | 2003-09-26 | 2005-11-30 | Schering Corp | Inhibidores macrociclicos de la serina proteasa ns3 del virus de la hepatitis c |
TW201245229A (en) | 2003-10-14 | 2012-11-16 | Hoffmann La Roche | Macrocyclic carboxylic acids and acylsulfonamides as inhibitors of HCV replication |
US8187874B2 (en) | 2003-10-27 | 2012-05-29 | Vertex Pharmaceuticals Incorporated | Drug discovery method |
US7494660B2 (en) | 2003-10-27 | 2009-02-24 | Vertex Pharmaceuticals Incorporated | HCV NS3-NS4A protease resistance mutants |
US7132504B2 (en) | 2003-11-12 | 2006-11-07 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
CA2546290A1 (fr) | 2003-11-20 | 2005-06-09 | Schering Corporation | Inhibiteurs depourvus de liaisons peptidiques de la protease ns3 du virus de l'hepatite c |
US7135462B2 (en) | 2003-11-20 | 2006-11-14 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US7309708B2 (en) | 2003-11-20 | 2007-12-18 | Birstol-Myers Squibb Company | Hepatitis C virus inhibitors |
DE602004019973D1 (de) | 2003-12-08 | 2009-04-23 | Boehringer Ingelheim Int | Abtrennung von ruthenium-nebenprodukten durch behandlung mit überkritischen flüssigkeiten |
GB0500020D0 (en) | 2005-01-04 | 2005-02-09 | Novartis Ag | Organic compounds |
WO2005070955A1 (fr) | 2004-01-21 | 2005-08-04 | Boehringer Ingelheim International Gmbh | Peptides macrocycliques actifs contre le virus de l'hepatite c |
CA2552317C (fr) | 2004-01-30 | 2013-12-10 | Medivir Ab | Inhibiteurs de la serine protease ns-3 du vhc |
SI1718608T1 (sl) | 2004-02-20 | 2013-11-29 | Boehringer Ingelheim International Gmbh | Inhibitorji virusne polimeraze |
US20070049593A1 (en) | 2004-02-24 | 2007-03-01 | Japan Tobacco Inc. | Tetracyclic fused heterocyclic compound and use thereof as HCV polymerase inhibitor |
WO2005080399A1 (fr) | 2004-02-24 | 2005-09-01 | Japan Tobacco Inc. | Composés hétérotétracycliques fondus et utilisation de ces composés en tant qu'inhibiteurs par polymérase du virus de l’hépatite c |
JP4745327B2 (ja) | 2004-02-27 | 2011-08-10 | シェーリング コーポレイション | C型肝炎ウイルスns3プロテアーゼのインヒビター |
RU2006134005A (ru) | 2004-02-27 | 2008-04-10 | Шеринг Корпорейшн (US) | Новые соединения, действующие как ингибиторы сериновой протеазы ns3 вируса гепатита с |
ATE434621T1 (de) | 2004-02-27 | 2009-07-15 | Schering Corp | Neue verbindungen als inhibitoren der ns3- serinprotease des hepatitis-c-virus |
US7816326B2 (en) | 2004-02-27 | 2010-10-19 | Schering Corporation | Sulfur compounds as inhibitors of hepatitis C virus NS3 serine protease |
CA2557495C (fr) | 2004-02-27 | 2014-04-15 | Schering Corporation | Composes soufres en tant qu'inhibiteurs de la protease serine ns3 du virus de l'hepatite c |
JP2007525512A (ja) | 2004-02-27 | 2007-09-06 | シェーリング コーポレイション | C型肝炎ウイルスns3セリンプロテアーゼのインヒビターとしての3,4−(シクロペンチル)−縮合プロリン化合物 |
ES2338666T3 (es) | 2004-03-15 | 2010-05-11 | Boehringer Ingelheim International Gmbh | Procedimiento para la preparacion de dipeptidos macrociclicos adecuados para el tratamiento de infecciones viricas de la hepatitis c. |
AP2006003763A0 (en) * | 2004-03-30 | 2006-10-31 | Intermune Inc | Macrocyclic compounds as inhibitors of viral replication |
MXPA06013404A (es) | 2004-05-20 | 2007-01-23 | Schering Corp | Prolinas sustituidas como inhibidores de serina proteasa ns3 de virus de hepatitis c. |
EP1753775B1 (fr) | 2004-05-25 | 2012-12-26 | Boehringer Ingelheim International GmbH | Processus de preparation d'inhibiteurs de protease hcv acyclique |
UY29016A1 (es) | 2004-07-20 | 2006-02-24 | Boehringer Ingelheim Int | Analogos de dipeptidos inhibidores de la hepatitis c |
WO2006007708A1 (fr) | 2004-07-20 | 2006-01-26 | Boehringer Engelheim International Gmbh | Analogues peptidiques inhibiteurs de l'hepatite c |
US7597884B2 (en) | 2004-08-09 | 2009-10-06 | Alios Biopharma, Inc. | Hyperglycosylated polypeptide variants and methods of use |
WO2006026352A1 (fr) | 2004-08-27 | 2006-03-09 | Schering Corporation | Composes d'acylsulfonamide inhibiteurs de la serine protease ns3 du virus de l'hepatite c |
WO2006030892A1 (fr) * | 2004-09-17 | 2006-03-23 | Nippon Shinyaku Co., Ltd. | Procede de production de composes heterocycliques |
EP1804821A4 (fr) | 2004-10-01 | 2009-07-15 | Vertex Pharma | Inhibition de la protease ns3-ns4a du vhc |
US7659263B2 (en) | 2004-11-12 | 2010-02-09 | Japan Tobacco Inc. | Thienopyrrole compound and use thereof as HCV polymerase inhibitor |
US7323447B2 (en) | 2005-02-08 | 2008-01-29 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
CN101160317B (zh) | 2005-03-08 | 2013-03-27 | 贝林格尔·英格海姆国际有限公司 | 制备大环化合物的方法 |
US7592336B2 (en) | 2005-05-10 | 2009-09-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
KR20080016597A (ko) | 2005-05-13 | 2008-02-21 | 바이로켐 파마 인코포레이티드 | 플라비바이러스 감염의 예방 또는 치료용 화합물 및 그의예방 또는 치료 방법 |
US7601686B2 (en) | 2005-07-11 | 2009-10-13 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
EP2305697A3 (fr) | 2005-07-25 | 2011-07-27 | Intermune, Inc. | Inhibiteurs macrocycliques de la multiplication du virus de L'Hépatite C |
PE20070211A1 (es) | 2005-07-29 | 2007-05-12 | Medivir Ab | Compuestos macrociclicos como inhibidores del virus de hepatitis c |
WO2007019674A1 (fr) | 2005-08-12 | 2007-02-22 | Boehringer Ingelheim International Gmbh | Inhibiteurs de polymerase virale |
DK1934243T3 (da) | 2005-09-09 | 2011-09-05 | Boehringer Ingelheim Int | Cykliserende metathesefremgangsmåde til fremstilling af makrocykliske peptider |
NZ568135A (en) | 2005-10-11 | 2011-06-30 | Array Biopharma Inc | Macrocyclic compounds and methods for inhibiting hepatitis C viral replication |
US7772183B2 (en) | 2005-10-12 | 2010-08-10 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US7741281B2 (en) | 2005-11-03 | 2010-06-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US7705138B2 (en) | 2005-11-11 | 2010-04-27 | Vertex Pharmaceuticals Incorporated | Hepatitis C virus variants |
US7816348B2 (en) | 2006-02-03 | 2010-10-19 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
US8017612B2 (en) | 2006-04-18 | 2011-09-13 | Japan Tobacco Inc. | Piperazine compound and use thereof as a HCV polymerase inhibitor |
CA2651762A1 (fr) | 2006-05-23 | 2007-11-29 | Irm Llc | Composes et compositions en tant qu'inhibiteurs de proteases activatrices de canal |
EP2049474B1 (fr) | 2006-07-11 | 2015-11-04 | Bristol-Myers Squibb Company | Inhibiteurs du virus de l'hépatite c |
EP1886685A1 (fr) | 2006-08-11 | 2008-02-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Méthodes, utilisations et compositions pour la modulation de la réplication du HCV par activation ou inhibition du récepteur farnesoid X |
RU2009109355A (ru) | 2006-08-17 | 2010-09-27 | БЕРИНГЕР ИНГЕЛЬХАЙМ ИНТЕРНАЦИОНАЛЬ ГмбХ (DE) | Ингибиторы вырусной полимеразы |
US8343477B2 (en) | 2006-11-01 | 2013-01-01 | Bristol-Myers Squibb Company | Inhibitors of hepatitis C virus |
US7772180B2 (en) | 2006-11-09 | 2010-08-10 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
SI2104674T1 (sl) | 2006-11-15 | 2013-09-30 | Vertex Pharmaceuticals (Canada) Incorporated | Tiofenski analogi za zdravljenje ali preprečevanje flavivirusnih infekcij |
US7763584B2 (en) | 2006-11-16 | 2010-07-27 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US8003604B2 (en) | 2006-11-16 | 2011-08-23 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US7888464B2 (en) | 2006-11-16 | 2011-02-15 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
AR067442A1 (es) | 2007-06-29 | 2009-10-14 | Gilead Sciences Inc | Compuestos antivirales |
WO2009005677A2 (fr) | 2007-06-29 | 2009-01-08 | Gilead Sciences, Inc. | Composés antiviraux |
WO2009018657A1 (fr) | 2007-08-03 | 2009-02-12 | Boehringer Ingelheim International Gmbh | Inhibiteurs de polymerase virale |
JP5529036B2 (ja) | 2007-12-05 | 2014-06-25 | エナンタ ファーマシューティカルズ インコーポレイテッド | フッ素化トリペプチドhcvセリンプロテアーゼ阻害剤 |
WO2009076747A1 (fr) | 2007-12-19 | 2009-06-25 | Boehringer Ingelheim International Gmbh | Inhibiteurs de polymérase virale |
US8202996B2 (en) | 2007-12-21 | 2012-06-19 | Bristol-Myers Squibb Company | Crystalline forms of N-(tert-butoxycarbonyl)-3-methyl-L-valyl-(4R)-4-((7-chloro-4-methoxy-1-isoquinolinyl)oxy)-N- ((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)-L-prolinamide |
US8163921B2 (en) | 2008-04-16 | 2012-04-24 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
WO2009148923A1 (fr) | 2008-05-29 | 2009-12-10 | Bristol-Myers Squibb Company | Inhibiteurs du virus de l’hépatite c |
US7964560B2 (en) | 2008-05-29 | 2011-06-21 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US8207341B2 (en) | 2008-09-04 | 2012-06-26 | Bristol-Myers Squibb Company | Process or synthesizing substituted isoquinolines |
UY32099A (es) | 2008-09-11 | 2010-04-30 | Enanta Pharm Inc | Inhibidores macrocíclicos de serina proteasas de hepatitis c |
PE20130307A1 (es) | 2008-09-16 | 2013-03-22 | Boehringer Ingelheim Int | Formas cristalinas de un derivado de 2-tiazolil-4-quinolinil-oxi, un potente inhibidor de hcv |
US8044087B2 (en) | 2008-09-29 | 2011-10-25 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US8563505B2 (en) | 2008-09-29 | 2013-10-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
WO2010039801A2 (fr) | 2008-10-02 | 2010-04-08 | The J. David Gladstone Institutes | Méthodes de traitement d’une infection par le virus de l’hépatite c |
US8283310B2 (en) | 2008-12-15 | 2012-10-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
CN102271699A (zh) | 2009-01-07 | 2011-12-07 | 西尼克斯公司 | 用于治疗hcv和hiv感染的环孢菌素衍生物 |
US8975247B2 (en) | 2009-03-18 | 2015-03-10 | The Board Of Trustees Of The Leland Stanford Junion University | Methods and compositions of treating a flaviviridae family viral infection |
CA2758072A1 (fr) | 2009-04-08 | 2010-10-14 | Idenix Pharmaceuticals, Inc. | Inhibiteurs macrocycliques de la serine protease |
US8512690B2 (en) | 2009-04-10 | 2013-08-20 | Novartis Ag | Derivatised proline containing peptide compounds as protease inhibitors |
US8936781B2 (en) | 2009-05-13 | 2015-01-20 | Enanta Pharmaceuticals, Inc. | Macrocyclic compounds as hepatitis C virus inhibitors |
CA2769652A1 (fr) | 2009-08-05 | 2011-02-10 | Idenix Pharmaceuticals, Inc. | Inhibiteurs macrocycliques de la serine protease macrocyclique utiles contre les infections virales, en particulier le virus de l?hepatite c |
JP5476859B2 (ja) * | 2009-08-25 | 2014-04-23 | 住友化学株式会社 | 光学活性な1−アミノ−2−エテニルシクロプロパン−1−カルボン酸エチルまたはその酸付加塩の製造方法、およびその製造方法に用いられる中間体 |
AU2010326225A1 (en) | 2009-11-25 | 2012-06-07 | Vertex Pharmaceuticals Incorporated | 5-alkynyl-thiophene-2-carboxylic acid derivatives and their use for the treatment or prevention of flavivirus infections |
SG181614A1 (en) | 2009-12-24 | 2012-07-30 | Vertex Pharma | Analogues for the treatment or prevention of flavivirus infections |
EP2528922B1 (fr) | 2010-01-27 | 2017-08-02 | AB Pharma Ltd | Composés polyhétérocycliques en tant qu'inhibiteurs du vhc |
MX2012010919A (es) | 2010-03-24 | 2013-02-01 | Vertex Pharma | Analogos para el tratamiento o prevencion de infecciones por flavivirus. |
WO2011119858A1 (fr) | 2010-03-24 | 2011-09-29 | Vertex Pharmaceuticals Incorporated | Analogues destinés au traitement ou à la prévention d'infections à flavivirus |
WO2011119860A1 (fr) | 2010-03-24 | 2011-09-29 | Vertex Pharmaceuticals Incorporated | Analogues pour traiter ou prévenir les infections à flavivirus |
AU2011232331A1 (en) | 2010-03-24 | 2012-10-11 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of Flavivirus infections |
WO2011156545A1 (fr) | 2010-06-09 | 2011-12-15 | Vertex Pharmaceuticals Incorporated | Modèle dynamique viral pour une polythérapie contre le vhc |
WO2011159826A2 (fr) | 2010-06-15 | 2011-12-22 | Vertex Pharmaceuticals Incorporated | Mutants de la protéase ns5b du vhc |
WO2012006070A1 (fr) | 2010-06-28 | 2012-01-12 | Vertex Pharmaceuticals Incorporated | Composés et méthodes de traitement ou de prévention d'infections à flavivirus |
EP2585448A1 (fr) | 2010-06-28 | 2013-05-01 | Vertex Pharmaceuticals Incorporated | Composés et méthodes de traitement ou de prévention d'infections à flavovirus |
WO2012006055A2 (fr) | 2010-06-28 | 2012-01-12 | Vertex Pharmaceuticals Incorporated | Composés et méthodes pour le traitement ou la prévention d'infections par flavivirus |
EP2606041A2 (fr) | 2010-08-17 | 2013-06-26 | Vertex Pharmaceuticals Incorporated | Composés et méthodes de traitement ou de prévention d'infections virales par des flaviviridae |
KR102128232B1 (ko) | 2010-09-21 | 2020-06-30 | 이난타 파마슈티칼스, 인코포레이티드 | 매크로사이클릭 프롤린 유도된 hcv 세린 프로테아제 억제제 |
KR20130120481A (ko) | 2010-10-08 | 2013-11-04 | 노파르티스 아게 | 술파미드 ns3 억제제의 비타민 e 제제 |
EA201390988A1 (ru) | 2010-12-30 | 2014-04-30 | Энанта Фармасьютикалз, Инк. | Фенантридиновые макроциклические ингибиторы сериновой протеазы вируса гепатита c |
WO2012092409A2 (fr) | 2010-12-30 | 2012-07-05 | Enanta Phararmaceuticals, Inc | Inhibiteurs macrocycliques de sérine protéase d'hépatite c |
AR085352A1 (es) | 2011-02-10 | 2013-09-25 | Idenix Pharmaceuticals Inc | Inhibidores macrociclicos de serina proteasa, sus composiciones farmaceuticas y su uso para tratar infecciones por hcv |
WO2012107589A1 (fr) | 2011-02-11 | 2012-08-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Méthodes et compositions pharmaceutiques pour le traitement et la prévention des infections à vhc |
CN103402972A (zh) * | 2011-03-10 | 2013-11-20 | 住友化学株式会社 | 光学活性1-氨基-2-乙烯基环丙烷甲酸酯的制造方法 |
US8957203B2 (en) | 2011-05-05 | 2015-02-17 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US10201584B1 (en) | 2011-05-17 | 2019-02-12 | Abbvie Inc. | Compositions and methods for treating HCV |
US8691757B2 (en) | 2011-06-15 | 2014-04-08 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
WO2012171332A1 (fr) | 2011-06-16 | 2012-12-20 | 爱博新药研发(上海)有限公司 | Composé hétérocyclique macrocyclique pour l'inhibition du virus de l'hépatite c, sa préparation et ses applications |
CN102807607B (zh) * | 2011-07-22 | 2013-10-23 | 爱博新药研发(上海)有限公司 | 抑制丙肝病毒的稠环杂环类化合物、其中间体及其应用 |
WO2013016499A1 (fr) | 2011-07-26 | 2013-01-31 | Vertex Pharmaceuticals Incorporated | Procédés de préparation de composés du thiophène |
TW201317223A (zh) | 2011-07-26 | 2013-05-01 | Vertex Pharma | 噻吩化合物 |
SG11201402899TA (en) | 2011-12-06 | 2014-07-30 | Univ Leland Stanford Junior | Methods and compositions for treating viral diseases |
EP2827876A4 (fr) | 2012-03-22 | 2015-10-28 | Alios Biopharma Inc | Combinaisons pharmaceutiques comprenant un analogue thionucléotidique |
EA025560B1 (ru) | 2012-10-19 | 2017-01-30 | Бристол-Майерс Сквибб Компани | Ингибиторы вируса гепатита с |
US9643999B2 (en) | 2012-11-02 | 2017-05-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
EP2914613B1 (fr) | 2012-11-02 | 2017-11-22 | Bristol-Myers Squibb Company | Inhibiteurs du virus de l'hépatite c |
US9334279B2 (en) | 2012-11-02 | 2016-05-10 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
WO2014070974A1 (fr) | 2012-11-05 | 2014-05-08 | Bristol-Myers Squibb Company | Inhibiteurs du virus de l'hépatite c |
US20150065439A1 (en) | 2013-02-28 | 2015-03-05 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions |
EP2964664B1 (fr) | 2013-03-07 | 2017-01-11 | Bristol-Myers Squibb Company | Inhibiteurs du virus de l'hépatite c |
WO2014138374A1 (fr) | 2013-03-08 | 2014-09-12 | Boehringer Ingelheim International Gmbh | Polythérapie par voie orale pour le traitement d'une infection par le vhc chez une sous-population spécifique de patients |
WO2015103490A1 (fr) | 2014-01-03 | 2015-07-09 | Abbvie, Inc. | Formes galéniques antivirales solides |
EP2899207A1 (fr) | 2014-01-28 | 2015-07-29 | Amikana.Biologics | Nouveau procédé pour tester l'inhibition de la protéase du HCV |
EP3891508A1 (fr) | 2018-12-04 | 2021-10-13 | Bristol-Myers Squibb Company | Procédés d'analyse utilisant une courbe d'étalonnage dans un échantillon par surveillance de réaction d'isotopologues multiples |
WO2023149981A1 (fr) * | 2022-02-07 | 2023-08-10 | Purdue Research Foundation | Composés pour le traitement du sars |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
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ES2169880T3 (es) * | 1996-10-18 | 2002-07-16 | Vertex Pharma | Inhibidores de proteasas de serina, particularmente de la proteasa ns3 del virus de la hepatitis c. |
EP1003775B1 (fr) * | 1997-08-11 | 2005-03-16 | Boehringer Ingelheim (Canada) Ltd. | Peptides inhibiteurs de l'hepatite c |
AR022061A1 (es) * | 1998-08-10 | 2002-09-04 | Boehringer Ingelheim Ca Ltd | Peptidos inhibidores de la hepatitis c, una composicion farmaceutica que los contiene, el uso de los mismos para preparar una composicion farmaceutica, el uso de un producto intermedio para la preparacion de estos peptidos y un procedimiento para la preparacion de un peptido analogo de los mismos. |
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