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2012 Fiscal Year Final Research Report

Study on Medicinal Chemistry of Reversible Cysteine Protease Inhibitors for the Treatment of Infectious Diseases

Research Project

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Project/Area Number 23659059
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Drug development chemistry
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

HAYASHI Yoshio  東京薬科大学, 薬学部, 教授 (10322562)

Project Period (FY) 2011 – 2012
Keywords医薬品化学 / 創薬化学 / プロテアーゼ阻害剤 / 重症急性呼吸器症候群 / ビオチニル化試薬 / 感染症 / 固相合成化学 / システインプロテアーゼ
Research Abstract

This work describes the establishment of common method for the development of cysteine protease inhibitors based on the aryl-ketone structure. As an example, from our preliminary inhibitor with a mild activity, we developed potent tri- and di-peptide-type SARS-CoV 3CL protease inhibitors. The results suggested that our aryl-ketone strategy worked effectively in the development of viral cysteine protease inhibitors. In addition, we developed a solid phase reagent that can introduce biotin to the target molecules by a very simple procedure in order to obtain a high affinity substrate, which can be changeable to the potent inhibitor by introducing the aryl-ketone structure.

  • Research Products

    (9 results)

All 2013 2012 2011 Other

All Journal Article (3 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article] Design and synthesis of new tripeptide-type SARS-CoV 3CL protease inhibitors containing an electrophilic arylketone moiety2013

    • Author(s)
      Sho Konno, Thanigaimalai Pillaiyar, Takehito Yamamoto, Kiyohiko Nakada, Rie Kakiuchi, Kentaro Takayama, Yuri Yamazaki, Fumika Yakushiji, Kenichi Akaji, Yoshiaki Kiso, Yuko Kawasaki, Shen-En Chen, Ernesto Freire,Yoshio Hayashi
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 21(2) Pages: 412-424

    • DOI

      DOI:org/10.1016/j.bmc.2012.11.017

  • [Journal Article] Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: Structure-activity relationship study2013

    • Author(s)
      Pillaiyar Thanigaimalai, Sho Konno, Takehito Yamamoto, Yuji Koiwai, Kentaro Takayama,Fumika Yakushiji, Kenichi Akaji, Yuko Kawasaki, Shen-En Chen, Aurash NaserTavakolian, Arne Schon, Ernesto Freire,Yoshio Hayashi
    • Journal Title

      Eur. J. Med. Chem

      Volume: 65 Pages: 436-447

    • DOI

      DOI:org/10.1016/j.ejmech.2013.05.005

  • [Journal Article] Development of a solidsupported biotinylation reagent for efficient biotin labeling of SH groups on small molecules2012

    • Author(s)
      Kentarou Fukumoto, Kumi Adachi, Akihiro Kajiyama, Yuri Yamazaki, Fumika Yakushiji, Yoshio Hayashi
    • Journal Title

      Tetrahedron Lett

      Volume: 53 Pages: 535-538

    • DOI

      DOI:org/10.1016/j.tetlet.2011.11.089

  • [Presentation] Development of tripeptide-type SARS coronavirus 3CL protease inhibitors with an electrophilic 2-benzothiazole ketone structure2012

    • Author(s)
      Takehito Yamamoto
    • Organizer
      244th ACS National Meeting & Exposition
    • Place of Presentation
      Philadelphia, PA, United States
    • Year and Date
      20120819-23
  • [Presentation] Peptidic cysteine protease inhibitors with an arylketone warhead for SARS Coronavirus2012

    • Author(s)
      Sho Konno
    • Organizer
      PEM6 (6th Peptide Engineering Meeting)
    • Place of Presentation
      Atlanta, Georgia, UAS
    • Year and Date
      2012-10-02
  • [Presentation] The development of tripeptide-type SARS Coronavirus 3CLprotease inhibitors: Structure-activity relationships at P4 moiety2012

    • Author(s)
      Takehito Yamamoto
    • Organizer
      The Pharmaceutical Society of Japan
    • Place of Presentation
      Sapparo, Japan
    • Year and Date
      2012-03-29
  • [Presentation] Development of SARS Coronovirus 3CL protease inhibitors with an electrophilic arylketone structure2011

    • Author(s)
      Sho Konno
    • Organizer
      8^<th> AFMC International Medicinal Chemistry Symposium
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2011-10-01
  • [Presentation] Design, Synthesis and Evaluation of Tripeptidomimetics with arylketone as inhibitors of SARS-CoV 3CL Protease2011

    • Author(s)
      Sho Konno
    • Organizer
      48^<th> Japanese Peptide Symposium
    • Place of Presentation
      Sapporo, Japan
    • Year and Date
      2011-09-28
  • [Remarks]

    • URL

      http://hinka-toyaku.s2.weblife.me/index.html

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Published: 2014-08-29   Modified: 2014-10-07  

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