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

Research Project

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
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (20 results)

All 2013 2012 2011 Other

All Journal Article (4 results) (of which Peer Reviewed: 3 results) Presentation (14 results) Remarks (2 results)

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

    • Author(s)
      S. Konno, P. Thanigaimalai, Shen-En Chen, Ernesto Freire, Y. Hayashi, 他9名
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 21 Issue: 2 Pages: 412-424

    • DOI

      10.1016/j.bmc.2012.11.017

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: Structure–activity relationship study2013

    • Author(s)
      Pillaiyar Thanigaimalai
    • Journal Title

      European Journal of Medicinal Chemistry

      Volume: in press Pages: 999-999

    • DOI

      10.1016/j.ejmech.2013.05.005

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [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 Issue: 5 Pages: 535-538

    • DOI

      10.1016/j.tetlet.2011.11.089

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Design, synthesis and evaluation of tripeptidommimetics with arylketone as inhibitors of SARS-CoV 3CL protease2012

    • Author(s)
      Sho Konno, Yoshio Hayashi 他10名
    • Journal Title

      Peptide Science 2011

      Volume: 2012 Pages: 151-154

    • Related Report
      2011 Research-status Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [Presentation] SH基選択的固相担持型ビオチニル化試薬の合成と低分子化合物の効率的ビオチン標識2012

    • Author(s)
      足立 久美、林 良雄 他4名
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Related Report
      2011 Research-status Report
  • [Presentation] トリペプチド型SARS コロナウイルス 3CL プロテアーゼ阻害剤の開発- P4 部位における構造活性相関研究 -2012

    • Author(s)
      山本 剛史、林 良雄 他10名
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Related Report
      2011 Research-status Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [Presentation] A new solid-support SH specific biotinylation reagent for the efficient biotin-labeling of small molecules2011

    • Author(s)
      Yoshio Hayashi, Fumika Yakushiji 他4人
    • Organizer
      22nd American Peptide Symposium
    • Place of Presentation
      San Diego, USA
    • Related Report
      2011 Research-status Report
  • [Presentation] Development of SARS Coronavirus 3CL Protease Inhibitors with an Electrophilic Aryl Ketone Structure2011

    • Author(s)
      Sho Konno, Yoshio Hayashi 他10人
    • Organizer
      8th AFMC International Medicinal Chemistry Symposium
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] 固相担持型SH基選択的ビオチン標識試薬の合成と低分子化合物への効率的ビオチン標識2011

    • Author(s)
      福元 謙太郎、林 良雄 他4人
    • Organizer
      日本ケミカルバイオロジー学会第6回年会
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] SARS-コロナウイルス3CLプロテアーゼ阻害剤のP4位における構造活性相関2011

    • Author(s)
      仲田 聖彦、林 良雄 他8名
    • Organizer
      第16回日本病態プロテアーゼ学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2011 Research-status Report
  • [Presentation] DESIGN, SYNTHESIS, AND EVALUATION OF TRIPEPTIDEMIMETICS WITH ARYLKETONE AS INHIBITORS OF SARS-COV 3CL PROTEASE2011

    • Author(s)
      Sho Konno, Yoshio Hayashi 他11名
    • Organizer
      第48回ペプチド討論会
    • Place of Presentation
      札幌
    • Related Report
      2011 Research-status Report
  • [Presentation] Development of SARS coronavirus 3CL protease inhibitors with an electrophilic aryl ketone structure

    • Author(s)
      Takehiro Yamamoto
    • Organizer
      244th American Chemical society National meeting & Exposition
    • Place of Presentation
      Philadelphia, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Peptidic cysteine protease inhibitors with an arylketone warhead for SARS Coronavirus

    • Author(s)
      Sho Konno
    • Organizer
      PEM6 (6th Peptide Engineering Meeting)
    • Place of Presentation
      Atlanta, USA
    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2012 Final Research Report
  • [Remarks] 東京薬科大学薬学部 薬品化学教室

    • URL

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

    • Related Report
      2012 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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