WO2006042478A8 - Small-molecule inhibitors of coronaviral main protease, their preparation and use - Google Patents

Small-molecule inhibitors of coronaviral main protease, their preparation and use

Info

Publication number
WO2006042478A8
WO2006042478A8 PCT/CN2005/001748 CN2005001748W WO2006042478A8 WO 2006042478 A8 WO2006042478 A8 WO 2006042478A8 CN 2005001748 W CN2005001748 W CN 2005001748W WO 2006042478 A8 WO2006042478 A8 WO 2006042478A8
Authority
WO
WIPO (PCT)
Prior art keywords
small
coronaviral
molecule inhibitors
preparation
main protease
Prior art date
Application number
PCT/CN2005/001748
Other languages
French (fr)
Chinese (zh)
Other versions
WO2006042478A1 (en
Inventor
Zihe Rao
Haitao Yang
Xiaoyu Xue
Mark Bartlam
Kailin Yang
Dawei Ma
Weiqing Xie
Original Assignee
Univ Tsinghua
Shanghai Inst Organic Chem
Zihe Rao
Haitao Yang
Xiaoyu Xue
Mark Bartlam
Kailin Yang
Dawei Ma
Weiqing Xie
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Univ Tsinghua, Shanghai Inst Organic Chem, Zihe Rao, Haitao Yang, Xiaoyu Xue, Mark Bartlam, Kailin Yang, Dawei Ma, Weiqing Xie filed Critical Univ Tsinghua
Publication of WO2006042478A1 publication Critical patent/WO2006042478A1/en
Publication of WO2006042478A8 publication Critical patent/WO2006042478A8/en

Links

Classifications

    • 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
    • C07K5/0205—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
    • C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Virology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Molecular Biology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The present invention is directed to a series of small-molecule inhibitors of general formula (I), which are designed on the crystal structure of SARS coronaviral main protease. Preparation of the said small-molecule inhibitors, pharmaceutical composition containing the same as well as their use in the manufacture of a medicament for treating or preventing a variety of coronaviral infections are also provided.
PCT/CN2005/001748 2004-10-22 2005-10-24 Small-molecule inhibitors of coronaviral main protease, their preparation and use WO2006042478A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN200410087721.7 2004-10-22
CNB2004100877217A CN100363346C (en) 2004-10-22 2004-10-22 Small molecular inhibiting agent for coronavirus main proteinase, its preparation method and uses

Publications (2)

Publication Number Publication Date
WO2006042478A1 WO2006042478A1 (en) 2006-04-27
WO2006042478A8 true WO2006042478A8 (en) 2006-07-13

Family

ID=36202685

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2005/001748 WO2006042478A1 (en) 2004-10-22 2005-10-24 Small-molecule inhibitors of coronaviral main protease, their preparation and use

Country Status (2)

Country Link
CN (1) CN100363346C (en)
WO (1) WO2006042478A1 (en)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103044338B (en) * 2012-12-12 2016-08-03 天津医科大学总医院 MiR-21 micromolecular inhibitor and application
CN104592349A (en) * 2015-02-15 2015-05-06 天津国际生物医药联合研究院 Small molecule inhibitor of coronavirus main proteases as well as preparation method and application of small molecule inhibitor
CN105412151A (en) * 2015-12-11 2016-03-23 天津国际生物医药联合研究院 Inhibitor aiming at coronavirus main protease, and application of Zn<2+>
CN105837487A (en) * 2016-03-17 2016-08-10 天津国际生物医药联合研究院 Small-molecule inhibitor against MERS-CoV main protease, and preparation method and application thereof
WO2017197377A1 (en) * 2016-05-13 2017-11-16 Emory University Peptidomimetics for the treatment of norovirus infection
CN115569133B (en) * 2020-02-26 2024-04-26 上海科技大学 Use of methylindigoindigo against coronaviruses
EP3912628A1 (en) * 2020-05-20 2021-11-24 Institut de Recherche en Semiochimie et Ethologie Appliquée Nucleoside analogues to inhibit the main protease of a coronavirus
US11351149B2 (en) * 2020-09-03 2022-06-07 Pfizer Inc. Nitrile-containing antiviral compounds
CN114149415A (en) * 2021-07-26 2022-03-08 中国药科大学 Peptide-like compound and derivative, preparation method, pharmaceutical composition and application thereof
CN117209558B (en) * 2023-08-14 2024-09-17 北京大学深圳研究生院 Use of Mpro protein inhibitors in medicaments for the treatment of novel coronavirus infections

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998043950A1 (en) * 1997-03-28 1998-10-08 Agouron Pharmaceuticals, Inc. Antipicornaviral compouds, compositions containing them, and methods for their use
DE69910762T2 (en) * 1998-04-30 2004-03-11 Agouron Pharmaceuticals, Inc., La Jolla ANTIPICORNAVIRAL COMPOUNDS, THEIR PRODUCTION AND USE
US6355807B1 (en) * 1999-08-24 2002-03-12 Agouron Pharmaceuticals, Inc. Efficient synthetic routes for the preparation of rhinovirus protease inhibitors and key intermediates
CN1922137A (en) * 2003-12-31 2007-02-28 太景生物科技股份有限公司 Protease inhibitors

Also Published As

Publication number Publication date
CN100363346C (en) 2008-01-23
CN1763002A (en) 2006-04-26
WO2006042478A1 (en) 2006-04-27

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