ZA200200881B - Antipicornaviral compounds and compositions, their pharmaceutical uses, and materials for their synthesis. - Google Patents
Antipicornaviral compounds and compositions, their pharmaceutical uses, and materials for their synthesis. Download PDFInfo
- Publication number
- ZA200200881B ZA200200881B ZA200200881A ZA200200881A ZA200200881B ZA 200200881 B ZA200200881 B ZA 200200881B ZA 200200881 A ZA200200881 A ZA 200200881A ZA 200200881 A ZA200200881 A ZA 200200881A ZA 200200881 B ZA200200881 B ZA 200200881B
- Authority
- ZA
- South Africa
- Prior art keywords
- pharmaceutically acceptable
- compound
- prodrug
- acceptable salt
- active metabolite
- Prior art date
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
-
- 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
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06043—Leu-amino acid
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
-
- 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
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
-
- 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
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14737399P | 1999-08-04 | 1999-08-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200200881B true ZA200200881B (en) | 2003-04-30 |
Family
ID=22521323
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200200881A ZA200200881B (en) | 1999-08-04 | 2002-01-31 | Antipicornaviral compounds and compositions, their pharmaceutical uses, and materials for their synthesis. |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US6534530B1 (xx) |
| EP (1) | EP1206484B1 (xx) |
| JP (1) | JP2003506457A (xx) |
| KR (1) | KR20020025964A (xx) |
| CN (1) | CN1372566A (xx) |
| AT (1) | ATE278707T1 (xx) |
| AU (1) | AU779321B2 (xx) |
| BR (1) | BR0012970A (xx) |
| CA (1) | CA2380647A1 (xx) |
| DE (1) | DE60014670T2 (xx) |
| DK (1) | DK1206484T3 (xx) |
| ES (1) | ES2230135T3 (xx) |
| HU (1) | HUP0203108A3 (xx) |
| MX (1) | MXPA02001179A (xx) |
| PL (1) | PL354030A1 (xx) |
| PT (1) | PT1206484E (xx) |
| WO (1) | WO2001010894A2 (xx) |
| ZA (1) | ZA200200881B (xx) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69910762T2 (de) | 1998-04-30 | 2004-03-11 | Agouron Pharmaceuticals, Inc., La Jolla | Antipicornavirale verbindungen, deren herstellung und verwendung |
| PE20020157A1 (es) | 1999-12-03 | 2002-02-22 | Agouron Pharma | Compuestos derivados de piridona como inhibidores de proteasas de picornaviral 3c, composiciones, sus usos farmaceuticos y materiales para su sintesis |
| PE20011277A1 (es) | 2000-04-14 | 2002-01-07 | Agouron Pharma | Compuestos y composiciones antipicornavirales, sus usos farmaceuticos y los materiales para su sintesis |
| CN1525957A (zh) | 2000-06-14 | 2004-09-01 | ������ҩ������˾ | 抗细小核糖核酸病毒的化合物与组合物,它们的药物用途,以及用于其合成的物质 |
| WO2002006280A2 (en) * | 2000-07-13 | 2002-01-24 | Millennium Pharamaceuticals, Inc. | INHIBITORS OF FACTOR Xa |
| CA2522700A1 (en) * | 2003-04-18 | 2004-11-04 | Cytovia, Inc. | Methods of treating diseases responsive to induction of apoptosis and screening assays |
| WO2004093860A1 (en) * | 2003-04-21 | 2004-11-04 | Pfizer Inc. | Inhibitors of sars related coronavirus proteinase |
| US20040235952A1 (en) * | 2003-05-05 | 2004-11-25 | Agouron Pharmaceuticals, Inc. | Inhibitors of severe acute respiratory syndrome (SARS) 3C-like proteinase |
| EP1628674A2 (en) * | 2003-05-06 | 2006-03-01 | Cytovia, Inc. | Protease inhibitors for coronaviruses and sars-cov and the use thereof |
| US7462594B2 (en) * | 2003-12-31 | 2008-12-09 | Taigen Biotechnology Co., Ltd. | Peptide-like compounds that inhibit coronaviral 3CL and flaviviridae viral proteases |
| CN1922137A (zh) * | 2003-12-31 | 2007-02-28 | 太景生物科技股份有限公司 | 蛋白酶抑制剂 |
| WO2005113580A1 (en) * | 2004-05-21 | 2005-12-01 | Pfizer Inc. | Anticoronviral compounds and compositions, their pharmaceutical uses and materials for their synthesis |
| WO2012162828A1 (en) | 2011-06-02 | 2012-12-06 | Socpra Sciences Santé Et Humaines S.E.C. | Matriptase inhibitors and uses thereof against orthomyxoviridae infections |
| CN102838523A (zh) * | 2011-06-23 | 2012-12-26 | 南开大学 | 抗肠病毒71(ev71)戊内酰胺类化合物及其制备方法和用途 |
| EP2760827A4 (en) | 2011-09-27 | 2015-06-24 | Univ Kansas State | ANTIVIRAL MEDIUM WITH A WIDE SPECTRUM AGAINST 3C OR 3C-SIMILAR PROTEASES FROM PICORNIVIRUS SUPERCLUSTS: PICORNIVERS, CALICIVIRES AND CORONA VIRUSES |
| CN103130710B (zh) * | 2011-11-29 | 2015-12-16 | 南开大学 | 抗肠病毒71(ev71)己内酰胺醛类化合物及其制备方法和用途 |
| CN103145608B (zh) * | 2011-12-07 | 2015-09-02 | 南开大学 | 抗肠病毒71(ev71)己内酰胺类化合物及其制备方法和用途 |
| WO2013166319A1 (en) | 2012-05-02 | 2013-11-07 | Kansas State University Research Foundation | Macrocyclic and peptidomimetic compounds as broad-spectrum antivirals against 3c or 3c-like proteases of picornaviruses, caliciviruses and coronaviruses |
| CN105518019A (zh) * | 2013-09-06 | 2016-04-20 | 桑多斯股份公司 | 肽环氧基酮的合成 |
| WO2018050631A1 (en) | 2016-09-13 | 2018-03-22 | Haplogen Gmbh | Antiviral compounds |
| US11124497B1 (en) | 2020-04-17 | 2021-09-21 | Pardes Biosciences, Inc. | Inhibitors of cysteine proteases and methods of use thereof |
| US11174231B1 (en) | 2020-06-09 | 2021-11-16 | Pardes Biosciences, Inc. | Inhibitors of cysteine proteases and methods of use thereof |
| US11351149B2 (en) | 2020-09-03 | 2022-06-07 | Pfizer Inc. | Nitrile-containing antiviral compounds |
| WO2022066776A1 (en) * | 2020-09-23 | 2022-03-31 | Cortexyme, Inc. | Compositions and methods for treatment of coronavirus infection |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4652676A (en) | 1985-05-06 | 1987-03-24 | General Foods Corporation | L-aminodicarboxylic acid alkenes |
| AU2251892A (en) | 1991-06-14 | 1993-01-12 | Chiron Corporation | Inhibitors of picornavirus proteases |
| US5374623A (en) | 1992-08-20 | 1994-12-20 | Prototek, Inc. | Cysteine protease inhibitors effective for in vivo use |
| US5486623A (en) | 1993-12-08 | 1996-01-23 | Prototek, Inc. | Cysteine protease inhibitors containing heterocyclic leaving groups |
| US5498616A (en) | 1994-11-04 | 1996-03-12 | Cephalon, Inc. | Cysteine protease and serine protease inhibitors |
| IT1281031B1 (it) | 1995-11-17 | 1998-02-11 | Carlo Chiaves | Struttura prefabbricata per la realizzazione di opere costruite a cielo aperto, particolarmente per cavalcavia autostradali, |
| IL120310A (en) | 1996-03-01 | 2002-02-10 | Akzo Nobel Nv | Serine protease inhibitors and pharmaceuticals containing them |
| US5856530A (en) | 1996-05-14 | 1999-01-05 | Agouron Pharmaceuticals, Inc. | Antipicornaviral compounds and methods for their use and preparation |
| AU722704B2 (en) | 1996-05-14 | 2000-08-10 | Agouron Pharmaceuticals, Inc. | Inhibitors of picornavirus 3c proteases and methods for their use and preparation |
| WO1997049668A1 (en) | 1996-06-13 | 1997-12-31 | Smithkline Beecham Corporation | Inhibitiors of cysteine protease |
| WO1998043950A1 (en) | 1997-03-28 | 1998-10-08 | Agouron Pharmaceuticals, Inc. | Antipicornaviral compouds, compositions containing them, and methods for their use |
| US6331554B1 (en) | 1997-03-28 | 2001-12-18 | Agouron Pharmaceuticals, Inc. | Antipicornaviral compounds, compositions containing them, and methods for their use |
| US6020371A (en) | 1997-03-28 | 2000-02-01 | Agouron Pharmaceuticals, Inc. | Antipicornaviral compounds compositions containing them and methods for their use |
| US5962487A (en) | 1997-12-16 | 1999-10-05 | Agouron Pharmaceuticals, Inc. | Antipicornaviral compounds and methods for their use and preparation |
| CN1524960A (zh) | 1999-08-24 | 2004-09-01 | ������ҩ������˾ | 制备异噁唑甲酰胺及其类似物的方法和中间体 |
| PE20010517A1 (es) | 1999-08-24 | 2001-05-16 | Agouron Pharma | Las rutas sinteticas eficientes para la preparacion de los inhibidores de la proteasa del rinovirus y los intermedios claves |
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- 2000-08-03 HU HU0203108A patent/HUP0203108A3/hu unknown
- 2000-08-03 US US09/631,708 patent/US6534530B1/en not_active Expired - Fee Related
- 2000-08-03 MX MXPA02001179A patent/MXPA02001179A/es active IP Right Grant
- 2000-08-03 BR BR0012970-4A patent/BR0012970A/pt not_active IP Right Cessation
- 2000-08-03 KR KR1020027001534A patent/KR20020025964A/ko not_active Application Discontinuation
- 2000-08-03 DK DK00952406T patent/DK1206484T3/da active
- 2000-08-03 PT PT00952406T patent/PT1206484E/pt unknown
- 2000-08-03 AT AT00952406T patent/ATE278707T1/de not_active IP Right Cessation
- 2000-08-03 CA CA002380647A patent/CA2380647A1/en not_active Abandoned
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- 2000-08-03 ES ES00952406T patent/ES2230135T3/es not_active Expired - Lifetime
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- 2000-08-03 EP EP00952406A patent/EP1206484B1/en not_active Expired - Lifetime
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| HUP0203108A3 (en) | 2004-07-28 |
| BR0012970A (pt) | 2002-04-30 |
| HUP0203108A2 (hu) | 2002-12-28 |
| PL354030A1 (en) | 2003-12-15 |
| MXPA02001179A (es) | 2002-07-30 |
| EP1206484B1 (en) | 2004-10-06 |
| ATE278707T1 (de) | 2004-10-15 |
| US6534530B1 (en) | 2003-03-18 |
| AU6511200A (en) | 2001-03-05 |
| PT1206484E (pt) | 2005-01-31 |
| WO2001010894A3 (en) | 2001-06-07 |
| JP2003506457A (ja) | 2003-02-18 |
| CA2380647A1 (en) | 2001-02-15 |
| DK1206484T3 (da) | 2005-01-24 |
| DE60014670D1 (de) | 2004-11-11 |
| KR20020025964A (ko) | 2002-04-04 |
| AU779321B2 (en) | 2005-01-20 |
| DE60014670T2 (de) | 2006-03-09 |
| EP1206484A2 (en) | 2002-05-22 |
| ES2230135T3 (es) | 2005-05-01 |
| CN1372566A (zh) | 2002-10-02 |
| WO2001010894A2 (en) | 2001-02-15 |
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