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Syntheses of novel ligands that maintain these unique biological activities in vivo

Research Project

Project/Area Number 25860011
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Chemical pharmacy
Research InstitutionTeikyo University

Principal Investigator

TAKANO MASASHI  帝京大学, 薬学部, 助教 (50386611)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsビタミンD / 合成化学 / 生理活性 / 有機化学 / 薬学 / 国際情報交換(米国) / 生理化学
Outline of Final Research Achievements

The synthesis of 1α,2α,25-trihydroxyvitamin D3, which is the major metabolite of 2α-(3-hydroxypropoxy)-1α,25-dihydroxyvitamin D3 (O2C3) by CYP3A4, has been achieved. Convergent syntheses of several novel 19-norvitamin D analogs with a tetrazole ring at the C2 position possessing the propyl linker have been achieved. These syntheses are characterized as useful syntheses with the high efficiency and yield, so that other ligands would be synthesized in these synthetic ways. Binding affinity for vitamin D receptor (VDR) of these ligands, transactivation activity of osteocalcin promoter in HOS cells, and metabolism by CYP24A1 have been also studied.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (8 results)

All 2015 2014 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (6 results)

  • [Journal Article] Synthesis and Preliminary Biological Evaluation of 2-[3-(Tetrazolyl)propyl]-1α,25-dihydroxy-19-norvitamin D32015

    • Author(s)
      Masashi Takano, Erika Higuchi, Kazunari Higashi, Keisuke Hirano, Akiko Takeuchi, Daisuke Sawada, and Atsushi Kittaka
    • Journal Title

      Heterocycles

      Volume: 90 Issue: 2 Pages: 1274-1287

    • DOI

      10.3987/com-14-s(k)108

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Synthesis and Biological Activity of 1α,2α,25-Trihydroxyvitamin D<sub>3</sub>: Active Metabolite of 2α-(3-Hydroxypropoxy)-1α,25-dihydroxyvitamin D<sub>3</sub> by Human CYP3A42014

    • Author(s)
      Masashi Takano, Saori Ohya, Kaori Yasuda, Miyu Nishikawa, Akiko Takeuchi, Daisuke Sawada, Toshiyuki Sakaki, and Atsushi Kittaka
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 62 Issue: 2 Pages: 182-184

    • DOI

      10.1248/cpb.c13-00646

    • NAID

      130003390755

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 2-(3-トリアゾリルプロピル)-1α,25(OH)2-19-ノルビタミンD3の合成2015

    • Author(s)
      高野真史、谷川有梨紗、小川圭瞳、宮田英美、上坂博翔、阪本祥一、橘高敦史
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸学院大学(兵庫県神戸市)
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 2α-(3-ヒドロキシプロピル)活性型ビタミンD3(MART-10)の合成と制がん活性2014

    • Author(s)
      高野真史、Kun-Chun Chiang、安田佳織、榊利之、Tai C. Chen、橘高敦史
    • Organizer
      第32回メディシナルケミストリーシンポジウム
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2014-11-26 – 2014-11-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 2α-ヘテロアリールプロピル-19-ノルビタミンD3の合成と生物活性評価2014

    • Author(s)
      高野真史、樋口恵理香、廣瀬七帆、竹内明子、澤田大介、橘高敦史
    • Organizer
      第44回複素環化学討論会
    • Place of Presentation
      札幌市民ホール(北海道札幌市)
    • Year and Date
      2014-09-10 – 2014-09-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 2α位にテトラゾールプロピル基を有する19-ノル型ビタミンD3の合成と生物活性評価2014

    • Author(s)
      高野真史、樋口恵理香、竹内明子、澤田大介、橘高敦史
    • Organizer
      日本ビタミン学会第66回大会
    • Place of Presentation
      姫路商工会議所(兵庫県姫路市)
    • Year and Date
      2014-06-13 – 2014-06-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] C5-C6 Coupling of MART-10 Synthesis and Its Clinical Implication in Cancer Treatment and Prevention

    • Author(s)
      高野真史
    • Organizer
      10th International Symposium on Carbanion Chemistry (ISCC-10)
    • Place of Presentation
      同志社大学(京都府)
    • Related Report
      2013 Research-status Report
  • [Presentation] 2-[3-(テトラゾール-2-イル)プロピル]1α,25(OH)2-19-ノルビタミンD3の合成

    • Author(s)
      高野真史
    • Organizer
      日本薬学会134年会
    • Place of Presentation
      熊本大学(熊本県)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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