Investigation of the mechanism of insulin secretion via Ca

• Project/Area Number: 23659049
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Hokkaido University
• Principal Investigator: SHUTO Satoshi 北海道大学, 大学院・薬学研究院, 教授 (70241346)
• Co-Investigator(Kenkyū-buntansha): SHIMAWAKI Ken 北海道大学, 大学院・薬学研究院, 特任助教 (60451407)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 医薬分子設計 / cADPR / β細胞 / ラジカル反応 / Huisegen反応 / 光反応

Research Abstract

As the key molecule to develop effective biological tools for theidentification of target proteins of cADPR in cells, 4” α-aziceethyl-cADPcR (3) was designedand successfully synthesized. 4” α-Azidoethyl-cADPcR (3) was shown to be biologically activeas we expected.

Research Products

• [Journal Article] Cyclopropane-Based Stereochemical Diversity-Oriented Conformational Restriction Strategy : Histamine Analog swith the4-Amino-2, 3-methano-1-(1H-imidazol-4-yl) butane Structure as Highly PotentHistamine H_3 and/or H4 Receptor Ligands. Org (2012)
  • Author(s): M. Watanabe, T. Kobayashi, T. Hirokawa, A. Yoshida, Y. Ito, S. Yamada, N. Orimoto, Y. Yamasaki, M. Arisawa, S. Shuto
  • Journal Title: Biomol. Chem Volume: 10 Issue: 4 Pages: 736-745
  • DOI: 10.1039/c1ob06496g
  • Peer Reviewed
• [Journal Article] Synthesis and discovery of N-carbonylpyrrolidine- or N-sulfonylpyrrolidine-containing uracil derivatives as potent human deoxyuridine triphosphatase inhibitors. (2012)
  • Author(s): H. Miyakoshi, S. Miyahara, T. Yokogawa, K. T. Chong, J. Taguchi, K. Endoh, W. Yano, T. Wakasa, H. Ueno, Y. Takao, M. Nomura, S. Shuto, H. Nagasawa, M. Fukuoka
  • Journal Title: J. Med. Chem. Volume: 55 Issue: 7 Pages: 2960-2969
  • DOI: 10.1021/jm201627n
  • Peer Reviewed
• [Journal Article] Discovery of a novel class of potent human deoxyuridine triphosphatase inhibitors remarkably enhancing the antitumor activity of thymidylate synthase inhibitors. (2012)
  • Author(s): S. Miyahara, H. Miyakoshi, T. Yokogawa, K. T. Chong, W. Yano, T. Wakasa, H. Ueno, Y. Takao, A. Fujioka, A. Hashimoto, K. Itou, K. Yamamura, M. Nomura, H. Nagasawa, S. Shuto, M. Fukuoka
  • Journal Title: J. Med. Chem. Volume: 55 Issue: 7 Pages: 2970-2980
  • DOI: 10.1021/jm201628y
  • Peer Reviewed
• [Journal Article] Ruthenium-catalyzed cycloisomerization of 1,3-dienes, for example, an N-dienyl-2-vinylaniline derivative, leading to a 3-Exomethylene-2-vinylindole derivative and its application to the synthesis of (±)-cinchonaminone (2012)
  • Author(s): Takao Ogawa
  • Journal Title: Eur. J. Org. Chem. Volume: - Issue: 16 Pages: 3084-3087
  • DOI: 10.1002/ejoc.201200260
  • Peer Reviewed
• [Journal Article] Discovery of Highly Potent Human Deoxyuridine Triphosphatase Inhibitors Based on the Conformation Restriction Strategy. (2012)
  • Author(s): S. Miyahara, H. Miyakoshi, T. Yokogawa, T. Muto, K. Endoh, W. Yano, T. Wakasa, H. Ueno, K. Itou, M. Nomura, H. Nagasawa, S. Shuto
  • Journal Title: J. Med. Chem. Volume: 55, Issue: 11 Pages: 5483-5496
  • DOI: 10.1021/jm300416h
  • Peer Reviewed
• [Journal Article] 1,2,3-Triazole-Containing Uracil Derivatives with Excellent Pharmacokinetics as a Novel Class of Potent Human Deoxyuridine Triphosphatase Inhibitors. (2012)
  • Author(s): H. Miyakoshi, S. Miyahara, K. Endoh, J. Taguchi, M. Nomura, Y. Takao, A. Fujioka, A. Hashimoto, K Itou, K. Yamamura, S. Shuto, H. Nagasawa, M. Fukuoka
  • Journal Title: J. Med. Chem. Volume: 55 Issue: 14 Pages: 6427-6437
  • DOI: 10.1021/jm3004174
  • Peer Reviewed
• [Journal Article] Structure Formation and Catalytic Activity of DNA in Organic Solvents (2012)
  • Author(s): Hiroshi Abe, Naoko Abe, Aya Shibata, Keiji Ito, Yoshiyuki Tanaka, Mika Ito, Hisao Saneyoshi, Satoshi Shuto, and Yoshihiro Ito
  • Journal Title: Angewandte Chemie International Edition Volume: 51 Issue: 26 Pages: 6475-6479
  • DOI: 10.1002/anie.201201111
  • Peer Reviewed
• [Journal Article] Ligand-Free Buchwald-Hartwig Aromatic Aminations of Aryl Halides Catalyzed by Low-Leaching and Highly Recyclable Sulfur-Modified Gold-Supported Palladium Material (2012)
  • Author(s): Mohammad Al-Amin, Tetsuo Honma, Naoyuki Hoshiya, Takatoshi Sato, Satoshi Shuto, Mitsuhiro Arisawa
  • Journal Title: Adv.Synth.Catal. Volume: 354 Issue: 6 Pages: 1061-1068
  • DOI: 10.1002/adsc.201100761
  • Peer Reviewed
• [Journal Article] Design and Synthesis of Indomethacin Analogues That Inhibit P-Glycoprotein and/or Multidrug Resistant Protein without Cox Inhibitory Activity (2012)
  • Author(s): Mitsuhiro Arisawa, Yayoi Kasaya, Tohru Obata, Takuma Sasaki, Tomonori Nakamura, Takuya Araki, Koujirou Yamamoto, Akito Sasaki, Akihito Yamano, Mika Ito, Hiroshi Abe, Yoshihiro Ito, and Satoshi Shuto
  • Journal Title: Journal of Medicinal Chemistry Volume: 55 Issue: 18 Pages: 8152-8163
  • DOI: 10.1021/jm301084z
  • Peer Reviewed
• [Journal Article] A Conformational Restriction Approach to β-secretase (BACE1) Inhibitors: Effect of a Cyclopropane Ring to Induce an Alternative Binding Mode (2012)
  • Author(s): Shuji Yonezawa
  • Journal Title: J. Med. Chem. Volume: 55 Issue: 20 Pages: 8838-8858
  • DOI: 10.1021/jm3011405
  • Peer Reviewed
• [Journal Article] One-pot ring-closing metathesis(RCM)/oxidation by an assisted tandem rutheniumcatalysis for the synthesis of 2-quinolones. (2012)
  • Author(s): H. Kato, T. Ishigame, N. Oshima, K. Shimawaki, M. Arisawa, S. Shuto
  • Journal Title: Adv. Synth. Cat. Volume: in press
• [Journal Article] Alkene isomerization/enamide-ene and diene metathesis for the construction of indoles, quinolines, benzofurans and chromenes with a chiral cyclopropane substituent. (2011)
  • Author(s): T. Kobayashi, M. Arisawa, S. Shuto
  • Journal Title: Org. Biomol. Chem. Volume: 9 Pages: 1219-1224
• [Journal Article] Design and synthesis of conformationally restricted indomethacin analogues that enhance doxorubicin cytotoxicity in multidrug resistant cells without cyclooxygenase inhibitory activity. (2011)
  • Author(s): M. Arisawa, Y. Kasaya, T. Obata, T. Sasaki, M. Ito, H. Abe, Y. Ito, A. Yamano, S. Shuto
  • Journal Title: ACS Med. Chem. Lett. Volume: 2 Pages: 353-357
• [Journal Article] Synthesis and characterization of a series of highly fluorogenic substrates for glutathione transferases, a general strategy. (2011)
  • Author(s): J. Zhang, A. Shibata, M. Ito, S. Shuto, Y. Ito, B. Mannervik, H. Abe. R. Morgenstern
  • Journal Title: J. Am. Chem. Soc. Volume: 133 Pages: 14109-14119
• [Journal Article] Characterization of new potential anti-cancer drugs designed to overcome glutathione transferase mediated resistance. (2011)
  • Author(s): K. Johansson, M. Ito, C. M. S. Schophuizen, S. Mathew, V. Heuser, J. Zhang, M. Shimoji, M. E. Vahter, W. H. Ang, P. J. Dyson, A. Shibata, S. Shuto, Y. Ito, H. Abe, R. Morgenstern
  • Journal Title: Mol. Pharmaceut. Volume: 8 Pages: 1698-1708
• [Journal Article] Synthesis of a series of 3,4-methanoarginines as side-chain conformationally restricted analogues of arginine. (2011)
  • Author(s): M. Watanabe, K. Yamaguchi, W. Tang, K. Yoshida, R. B. Silverman, M. Arisawa, S. Shuto
  • Journal Title: Bioorg. Med. Chem. Volume: 19 Pages: 5984-5988
• [Journal Article] Design and Synthesis of Cyclic ADP-4-Thioribose as a Stable Equivalent of Cyclic ADP-Ribose, a Ca-Mobilizing Second Messenger
  • Author(s): T. Tsuzuki, N. Sakaguchi, T. Kudoh, S. Takano, M. Uehara, T. Murayama, T. Sakurai, M. Hashii, H. Higashida, K. Weber, A. H. Guse, T. Kameda, T. Hirokawa, Y. Kumaki, B. V. L. Potter,H. Fukuda, M. Arisawa, S. Shuto
  • Journal Title: Angew.Chem. Int. Ed Volume: (印刷中)
• [Presentation] Ca動員セカンドメッセンジャーの化学 ―細胞内情報伝達系の創薬標的化を目指してー (2012)
  • Author(s): 周東 智
  • Organizer: 産業総合研究所・分子標的創薬セミナー2000.12.6
  • Place of Presentation: 産業技術総合研究所生命情報工学研究センター（ 東京都）
  • Invited
• [Presentation] Ca動員セカンドメッセンジャーの化学-細胞内情報伝達系の創薬標的化を目指して (2000)
  • Author(s): 周東智
  • Organizer: 産業総合研究所・分子標的創薬セミナー
  • Place of Presentation: 産業技術総合研究所生命情報工学研究センター(東京都江東区)
  • Year and Date: 2000-12-06