AU2004230946A1 - Inhibitors of serine proteases, particularly HCV NS3-NS4A protease - Google Patents
Inhibitors of serine proteases, particularly HCV NS3-NS4A protease Download PDFInfo
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- AU2004230946A1 AU2004230946A1 AU2004230946A AU2004230946A AU2004230946A1 AU 2004230946 A1 AU2004230946 A1 AU 2004230946A1 AU 2004230946 A AU2004230946 A AU 2004230946A AU 2004230946 A AU2004230946 A AU 2004230946A AU 2004230946 A1 AU2004230946 A1 AU 2004230946A1
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- aliphatic
- cycloalkyl
- aryl
- clo
- heteroaryl
- Prior art date
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- 229960005486 vaccine Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000006514 viral protein processing Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- HGPHQCSSTFBAML-UHFFFAOYSA-M zinc;2-methylpropane;bromide Chemical compound Br[Zn+].C[C-](C)C HGPHQCSSTFBAML-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- 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
- C07D403/02—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
-
- 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
- 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
- C07D417/02—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
-
- 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
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2011203054A AU2011203054B2 (en) | 2003-04-11 | 2011-06-23 | Inhibitors of Serine Proteases, Particularly HCV NS3-NS4A Protease |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/412,600 | 2003-04-11 | ||
| US10/412,600 US7273885B2 (en) | 2002-04-11 | 2003-04-11 | Inhibitors of serine proteases, particularly HCV NS3-NS4A protease |
| US51376503P | 2003-10-23 | 2003-10-23 | |
| US60/513,765 | 2003-10-23 | ||
| PCT/US2004/011012 WO2004092162A1 (en) | 2003-04-11 | 2004-04-09 | Inhibitors of serine proteases, particularly hcv ns3-ns4a protease |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2011203054A Division AU2011203054B2 (en) | 2003-04-11 | 2011-06-23 | Inhibitors of Serine Proteases, Particularly HCV NS3-NS4A Protease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2004230946A1 true AU2004230946A1 (en) | 2004-10-28 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2004230946A Abandoned AU2004230946A1 (en) | 2003-04-11 | 2004-04-09 | Inhibitors of serine proteases, particularly HCV NS3-NS4A protease |
Country Status (10)
| Country | Link |
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| US (3) | US20050090450A1 (enExample) |
| EP (2) | EP1636208B1 (enExample) |
| JP (2) | JP2006526011A (enExample) |
| CN (1) | CN100453553C (enExample) |
| AR (1) | AR044513A1 (enExample) |
| AT (1) | ATE547412T1 (enExample) |
| AU (1) | AU2004230946A1 (enExample) |
| CA (1) | CA2521678A1 (enExample) |
| ES (1) | ES2381548T3 (enExample) |
| WO (1) | WO2004092162A1 (enExample) |
Families Citing this family (80)
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| CN1133649C (zh) | 1996-10-18 | 2004-01-07 | 沃泰克斯药物股份有限公司 | 丝氨酸蛋白酶、特别是丙型肝炎病毒ns3蛋白酶的抑制剂 |
| ATE297946T1 (de) * | 2000-04-03 | 2005-07-15 | Vertex Pharma | Inhibitoren von serin proteasen, speziell der hepatitis-c-virus ns3-protease |
| SV2003000617A (es) | 2000-08-31 | 2003-01-13 | Lilly Co Eli | Inhibidores de la proteasa peptidomimetica ref. x-14912m |
| PL373399A1 (en) * | 2002-04-11 | 2005-08-22 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hcv ns3-ns4a protease |
| CN102020700A (zh) * | 2003-07-18 | 2011-04-20 | 沃泰克斯药物股份有限公司 | 丝氨酸蛋白酶抑制剂、特别是hcv ns3-ns4a蛋白酶抑制剂 |
| MY148123A (en) * | 2003-09-05 | 2013-02-28 | Vertex Pharma | Inhibitors of serine proteases, particularly hcv ns3-ns4a protease |
| EP1664091A1 (en) | 2003-09-18 | 2006-06-07 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hcv ns3-ns4a protease |
| KR20060130027A (ko) * | 2003-10-10 | 2006-12-18 | 버텍스 파마슈티칼스 인코포레이티드 | 세린 프로테아제, 특히 hcv ns3-ns4a 프로테아제의억제제 |
| US7365092B2 (en) * | 2003-10-10 | 2008-04-29 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly HCV NS3-NS4A protease |
| CN1938332B (zh) * | 2004-02-04 | 2011-10-19 | 沃泰克斯药物股份有限公司 | 丝氨酸蛋白酶、特别是hcv ns3-ns4a蛋白酶的抑制剂 |
| NZ563909A (en) | 2005-05-13 | 2011-10-28 | Virochem Pharma Inc | Thiophene derivatives and their use for the treatment or prevention of flavivirus infections |
| EP2402331A1 (en) * | 2005-08-02 | 2012-01-04 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases |
| US8399615B2 (en) | 2005-08-19 | 2013-03-19 | Vertex Pharmaceuticals Incorporated | Processes and intermediates |
| AR055395A1 (es) | 2005-08-26 | 2007-08-22 | Vertex Pharma | Compuestos inhibidores de la actividad de la serina proteasa ns3-ns4a del virus de la hepatitis c |
| US7964624B1 (en) | 2005-08-26 | 2011-06-21 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases |
| US7705138B2 (en) | 2005-11-11 | 2010-04-27 | Vertex Pharmaceuticals Incorporated | Hepatitis C virus variants |
| KR20140098867A (ko) | 2005-11-11 | 2014-08-08 | 버텍스 파마슈티칼스 인코포레이티드 | C형 간염 바이러스 변이체 |
| US7456165B2 (en) * | 2006-02-08 | 2008-11-25 | Bristol-Myers Squibb Company | HCV NS5B inhibitors |
| US8039475B2 (en) | 2006-02-27 | 2011-10-18 | Vertex Pharmaceuticals Incorporated | Co-crystals and pharmaceutical compositions comprising the same |
| KR20080112303A (ko) | 2006-03-16 | 2008-12-24 | 버텍스 파마슈티칼스 인코포레이티드 | 중수소화 c형 간염 프로테아제 억제제 |
| WO2007111866A2 (en) * | 2006-03-23 | 2007-10-04 | Schering Corporation | Combinations of hcv protease inhibitor(s) and cyp3a4 inhibitor(s), and methods of treatment related thereto |
| NZ576780A (en) | 2006-11-15 | 2011-12-22 | Virochem Pharma Inc | Thiophene analogues for the treatment or prevention of flavivirus infections |
| EP2134717A2 (en) * | 2007-02-27 | 2009-12-23 | Vertex Pharmceuticals Incorporated | Inhibitors of serine proteases |
| PT2114924E (pt) * | 2007-02-27 | 2012-04-03 | Vertex Pharma | Co-cristais e composições farmacêuticas que compreendem os mesmos |
| US20090004140A1 (en) * | 2007-06-26 | 2009-01-01 | Yao-Ling Qiu | 4-substituted pyrrolidine as anti-infectives |
| US20090022689A1 (en) * | 2007-07-18 | 2009-01-22 | Yat Sun Or | C4-spiro-pyrrolidine antivirals |
| JP5443360B2 (ja) | 2007-08-30 | 2014-03-19 | 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 | 共結晶体およびそれを含む医薬組成物 |
| US20090060874A1 (en) * | 2007-09-05 | 2009-03-05 | Yao-Ling Qiu | Bicyclic pyrrolidine derivatives |
| TW200936131A (en) | 2008-02-04 | 2009-09-01 | Idenix Pharmaceuticals Inc | Macrocyclic serine protease inhibitors |
| US20090233972A1 (en) * | 2008-03-12 | 2009-09-17 | Yat Sun Or | Substituted heterocycles as anti-infectives |
| US20090324544A1 (en) * | 2008-06-11 | 2009-12-31 | Yao-Ling Qiu | Substituted cyclic pyrrolidine derivatives |
| US20090326019A1 (en) * | 2008-06-11 | 2009-12-31 | Yat Sun Or | 3,4-bicyclic pyrrolidine antivirals |
| US20100074863A1 (en) * | 2008-09-17 | 2010-03-25 | Yat Sun Or | Anti-infective pyrrolidine derivatives and analogs |
| US8102720B2 (en) * | 2009-02-02 | 2012-01-24 | Qualcomm Incorporated | System and method of pulse generation |
| EP2403860B1 (en) | 2009-03-04 | 2015-11-04 | IDENIX Pharmaceuticals, Inc. | Phosphothiophene and phosphothiazole as hcv polymerase inhibitors |
| WO2010118078A1 (en) | 2009-04-08 | 2010-10-14 | Idenix Pharmaceuticals, Inc. | Macrocyclic serine protease inhibitors |
| US8980920B2 (en) | 2009-05-29 | 2015-03-17 | Merck Sharp & Dohme Corp. | Antiviral compounds of three linked aryl moieties to treat diseases such as hepatitis C |
| CA2769652A1 (en) | 2009-08-05 | 2011-02-10 | Idenix Pharmaceuticals, Inc. | Macrocyclic serine protease inhibitors useful against viral infections, particularly hcv |
| EP2477980B1 (en) | 2009-09-15 | 2016-06-08 | Taigen Biotechnology Co., Ltd. | Hcv protease inhibitors |
| WO2011063076A1 (en) | 2009-11-19 | 2011-05-26 | Itherx Pharmaceuticals, Inc. | Methods of treating hepatitis c virus with oxoacetamide compounds |
| 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 |
| EP2503881B1 (en) | 2009-11-25 | 2015-05-13 | Merck Sharp & Dohme Corp. | Fused tricyclic compounds and derivatives thereof useful for the treatment of viral diseases |
| AR079528A1 (es) | 2009-12-18 | 2012-02-01 | Idenix Pharmaceuticals Inc | Inhibidores de arileno o heteroarileno 5,5-fusionado del virus de la hepatitis c |
| US20130156731A1 (en) | 2009-12-22 | 2013-06-20 | Kevin X. Chen | Fused tricyclic compounds and methods of use thereof for the treatment of viral diseas |
| CA2784036A1 (en) | 2009-12-24 | 2011-06-30 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
| US8609635B2 (en) | 2010-03-09 | 2013-12-17 | Merck Sharp & Dohme Corp. | Fused tricyclic silyl compounds and methods of use thereof for the treatment of viral diseases |
| WO2011119860A1 (en) | 2010-03-24 | 2011-09-29 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
| WO2011119858A1 (en) | 2010-03-24 | 2011-09-29 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
| CA2794145A1 (en) | 2010-03-24 | 2011-09-29 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
| AU2011232348A1 (en) | 2010-03-24 | 2012-10-11 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of Flavivirus infections |
| WO2011156545A1 (en) | 2010-06-09 | 2011-12-15 | Vertex Pharmaceuticals Incorporated | Viral dynamic model for hcv combination therapy |
| EP2582717A2 (en) | 2010-06-15 | 2013-04-24 | Vertex Pharmaceuticals Incorporated | Hcv ns5b polymerase mutants |
| EP2585448A1 (en) | 2010-06-28 | 2013-05-01 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of flavivirus infections |
| MX2012014918A (es) | 2010-06-28 | 2013-04-08 | Vertex Pharma | Compuestos y metodos para tratamiento o prevencion de infecciones por flavivirus. |
| WO2012006070A1 (en) | 2010-06-28 | 2012-01-12 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of flavivirus infections |
| AU2011286276A1 (en) | 2010-07-26 | 2013-01-24 | Merck Sharp & Dohme Corp. | Substituted biphenylene compounds and methods of use thereof for the treatment of viral diseases |
| AU2011292040A1 (en) | 2010-08-17 | 2013-03-07 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of Flaviviridae viral infections |
| CA2812779A1 (en) | 2010-09-29 | 2012-04-19 | Merck Sharp & Dohme Corp. | Fused tetracycle derivatives and methods of use thereof for the treatment of viral diseases |
| TW201309690A (zh) | 2011-02-10 | 2013-03-01 | Idenix Pharmaceuticals Inc | 巨環絲胺酸蛋白酶抑制劑,其醫藥組合物及其於治療hcv感染之用途 |
| US20120252721A1 (en) | 2011-03-31 | 2012-10-04 | Idenix Pharmaceuticals, Inc. | Methods for treating drug-resistant hepatitis c virus infection with a 5,5-fused arylene or heteroarylene hepatitis c virus inhibitor |
| EA201391519A1 (ru) | 2011-04-13 | 2014-03-31 | Мерк Шарп И Доум Корп. | 2'-замещенные нуклеозидные производные и способы их применения для лечения вирусных заболеваний |
| WO2012142075A1 (en) | 2011-04-13 | 2012-10-18 | Merck Sharp & Dohme Corp. | 2'-azido substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases |
| WO2013016501A1 (en) | 2011-07-26 | 2013-01-31 | Vertex Pharmaceuticals Incorporated | Formulations of thiophene compounds |
| WO2013016499A1 (en) | 2011-07-26 | 2013-01-31 | Vertex Pharmaceuticals Incorporated | Methods for preparation of thiophene compounds |
| WO2013033900A1 (en) | 2011-09-08 | 2013-03-14 | Merck Sharp & Dohme Corp. | Tetracyclic heterocycle compounds and methods of use thereof for the treatment of viral diseases |
| WO2013033901A1 (en) | 2011-09-08 | 2013-03-14 | Merck Sharp & Dohme Corp. | Heterocyclic-substituted benzofuran derivatives and methods of use thereof for the treatment of viral diseases |
| WO2013033899A1 (en) | 2011-09-08 | 2013-03-14 | Merck Sharp & Dohme Corp. | Substituted benzofuran compounds and methods of use thereof for the treatment of viral diseases |
| WO2013039876A1 (en) | 2011-09-14 | 2013-03-21 | Merck Sharp & Dohme Corp. | Silyl-containing heterocyclic compounds and methods of use thereof for the treatment of viral diseases |
| WO2013072328A1 (en) | 2011-11-14 | 2013-05-23 | Sanofi | Use of telaprevir and related compounds in atherosclerosis, heart failure, renal diseases, liver diseases or inflammatory diseases |
| NZ630805A (en) | 2012-03-22 | 2016-01-29 | Alios Biopharma Inc | Pharmaceutical combinations comprising a thionucleotide analog |
| KR102161077B1 (ko) * | 2012-06-29 | 2020-09-29 | 가부시키가이샤 한도오따이 에네루기 켄큐쇼 | 반도체 장치 |
| WO2014053533A1 (en) | 2012-10-05 | 2014-04-10 | Sanofi | Use of substituted 3-heteroaroylamino-propionic acid derivatives as pharmaceuticals for prevention/treatment of atrial fibrillation |
| US20150065439A1 (en) | 2013-02-28 | 2015-03-05 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions |
| EP3046924A1 (en) | 2013-09-20 | 2016-07-27 | IDENIX Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
| EP3063140A4 (en) | 2013-10-30 | 2017-11-08 | Merck Sharp & Dohme Corp. | Pseudopolymorphs of an hcv ns5a inhibitor and uses thereof |
| US20170066779A1 (en) | 2014-03-05 | 2017-03-09 | Idenix Pharmaceuticals Llc | Solid forms of a flaviviridae virus inhibitor compound and salts thereof |
| WO2015134561A1 (en) | 2014-03-05 | 2015-09-11 | Idenix Pharmaceuticals, Inc. | Pharmaceutical compositions comprising a 5,5-fused heteroarylene flaviviridae inhibitor and their use for treating or preventing flaviviridae infection |
| WO2017222915A1 (en) | 2016-06-21 | 2017-12-28 | Inception 4, Inc. | Heterocyclic prolinamide derivatives |
| EP3472151A4 (en) | 2016-06-21 | 2020-03-04 | Orion Ophthalmology LLC | CARBOCYCLIC PROLINAMIDE DERIVATIVES |
| US12083099B2 (en) | 2020-10-28 | 2024-09-10 | Accencio LLC | Methods of treating symptoms of coronavirus infection with viral protease inhibitors |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US534410A (en) * | 1895-02-19 | Sylvania | ||
| US4499082A (en) * | 1983-12-05 | 1985-02-12 | E. I. Du Pont De Nemours And Company | α-Aminoboronic acid peptides |
| NZ235155A (en) * | 1989-09-11 | 1993-04-28 | Merrell Dow Pharma | Peptidase substrates in which the carboxy terminal group has been replaced by a tricarbonyl radical |
| EP0564561A4 (en) * | 1990-12-28 | 1994-08-10 | Georgia Tech Res Inst | Peptides ketoamides, ketoacids, and ketoesters |
| US5384410A (en) | 1993-03-24 | 1995-01-24 | The Du Pont Merck Pharmaceutical Company | Removal of boronic acid protecting groups by transesterification |
| US5807876A (en) | 1996-04-23 | 1998-09-15 | Vertex Pharmaceuticals Incorporated | Inhibitors of IMPDH enzyme |
| CN1133649C (zh) | 1996-10-18 | 2004-01-07 | 沃泰克斯药物股份有限公司 | 丝氨酸蛋白酶、特别是丙型肝炎病毒ns3蛋白酶的抑制剂 |
| GB9623908D0 (en) * | 1996-11-18 | 1997-01-08 | Hoffmann La Roche | Amino acid derivatives |
| GB9707659D0 (en) * | 1997-04-16 | 1997-06-04 | Peptide Therapeutics Ltd | Hepatitis C NS3 Protease inhibitors |
| EP1066247B1 (en) * | 1998-03-31 | 2006-11-22 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hepatitis c virus ns3 protease |
| CN1196687C (zh) | 1999-03-19 | 2005-04-13 | 沃泰克斯药物股份有限公司 | Impdh酶抑制剂 |
| AU5788800A (en) * | 1999-07-07 | 2001-01-22 | Du Pont Pharmaceuticals Company | Peptide boronic acid inhibitors of hepatitis c virus protease |
| WO2001040262A1 (en) * | 1999-12-03 | 2001-06-07 | Bristol-Myers Squibb Pharma Company | Alpha-ketoamide inhibitors of hepatitis c virus ns3 protease |
| ATE297946T1 (de) * | 2000-04-03 | 2005-07-15 | Vertex Pharma | Inhibitoren von serin proteasen, speziell der hepatitis-c-virus ns3-protease |
| SI1385870T1 (sl) | 2000-07-21 | 2010-08-31 | Schering Corp | Peptidi kot NS3-serin proteazni inhibitorji virusa hepatitisa C |
| AR029851A1 (es) * | 2000-07-21 | 2003-07-16 | Dendreon Corp | Nuevos peptidos como inhibidores de ns3-serina proteasa del virus de hepatitis c |
| EP1301527A2 (en) * | 2000-07-21 | 2003-04-16 | Corvas International, Inc. | Peptides as ns3-serine protease inhibitors of hepatitis c virus |
| SV2003000617A (es) * | 2000-08-31 | 2003-01-13 | Lilly Co Eli | Inhibidores de la proteasa peptidomimetica ref. x-14912m |
| PL373399A1 (en) * | 2002-04-11 | 2005-08-22 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hcv ns3-ns4a protease |
-
2004
- 2004-04-09 JP JP2006509873A patent/JP2006526011A/ja active Pending
- 2004-04-09 AU AU2004230946A patent/AU2004230946A1/en not_active Abandoned
- 2004-04-09 CN CNB2004800140478A patent/CN100453553C/zh not_active Expired - Fee Related
- 2004-04-09 WO PCT/US2004/011012 patent/WO2004092162A1/en not_active Ceased
- 2004-04-09 AT AT04759362T patent/ATE547412T1/de active
- 2004-04-09 EP EP04759362A patent/EP1636208B1/en not_active Expired - Lifetime
- 2004-04-09 US US10/821,793 patent/US20050090450A1/en not_active Abandoned
- 2004-04-09 ES ES04759362T patent/ES2381548T3/es not_active Expired - Lifetime
- 2004-04-09 EP EP10178023A patent/EP2332935A1/en not_active Withdrawn
- 2004-04-09 CA CA002521678A patent/CA2521678A1/en not_active Abandoned
- 2004-04-12 AR ARP040101227A patent/AR044513A1/es unknown
-
2008
- 2008-07-08 US US12/169,209 patent/US20090022688A1/en not_active Abandoned
-
2010
- 2010-10-29 JP JP2010243570A patent/JP2011068655A/ja active Pending
-
2011
- 2011-09-21 US US13/238,386 patent/US8618152B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1795188A (zh) | 2006-06-28 |
| EP1636208A1 (en) | 2006-03-22 |
| WO2004092162A1 (en) | 2004-10-28 |
| ES2381548T3 (es) | 2012-05-29 |
| EP2332935A1 (en) | 2011-06-15 |
| JP2006526011A (ja) | 2006-11-16 |
| CA2521678A1 (en) | 2004-10-28 |
| US20050090450A1 (en) | 2005-04-28 |
| US8618152B2 (en) | 2013-12-31 |
| CN100453553C (zh) | 2009-01-21 |
| HK1090644A1 (zh) | 2006-12-29 |
| US20090022688A1 (en) | 2009-01-22 |
| EP1636208B1 (en) | 2012-02-29 |
| ATE547412T1 (de) | 2012-03-15 |
| US20120014914A1 (en) | 2012-01-19 |
| AR044513A1 (es) | 2005-09-14 |
| JP2011068655A (ja) | 2011-04-07 |
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| Date | Code | Title | Description |
|---|---|---|---|
| MK5 | Application lapsed section 142(2)(e) - patent request and compl. specification not accepted |