Structure-activity relationship of atpenin A5 derivatives as complex II selective inhibitors

• Project/Area Number: 23790140
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Kitasato University
• Principal Investigator: OHTAWA Masaki 北里大学, 薬学部, 助教 (70453503)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 構造活性相関 / complex II / 天然有機化合物 / 創薬化学

Research Abstract

Structure-activity relationship of atpenin A5 focused on 2-position and substituents of the side chain has been achieved. On this study, the importance of stereochemistry and the presence of each methyl and chloro groups on the side chain were elucidated.

Research Products

• [Journal Article] Synthesis and Structure-Activity Relationship of Pyripyropene A Derivatives as Potent and Selective Acyl-CoA:cholesterol Acyltransferase 2 (ACAT2) Inhibitors: Part 1 (2013)
  • Author(s): Ohtawa Masaki
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 23 Issue: 5 Pages: 1285-1287
  • DOI: 10.1016/j.bmcl.2012.12.099
  • Peer Reviewed
• [Journal Article] Potentiation of Bleomycin in Jurkat Cells by Fungal Pycnidione (2012)
  • Author(s): Kaneko M, Matsuda D, Ohtawa M, Fukuda T, Nagamitsu T, Yamori T, Tomoda H.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 35 Issue: 1 Pages: 18-28
  • DOI: 10.1248/bpb.35.18
  • NAID: 130001872337
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed
• [Journal Article] Stereoselective Total Synthesis of Atpenins A4 and B, Harzianopyridone, and NBRI23477 B (2012)
  • Author(s): Masaki Ohtawa
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 60 Issue: 7 Pages: 898-906
  • DOI: 10.1248/cpb.c12-00266
  • NAID: 130001852500
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed
• [Journal Article] Total Synthesis of Pyripyropene A (2011)
  • Author(s): Odani Atsuki
  • Journal Title: Tetrahedron Volume: 67 Issue: 42 Pages: 8195-8203
  • DOI: 10.1016/j.tet.2011.06.084
  • Peer Reviewed
• [Presentation] Atpenin A5 の構造活性相関研究 (2012)
  • Author(s): 樋浦徹 (大多和正樹)
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学札幌キャンパス(北海道)
• [Presentation] Atpenin A5 の構造活性相関研究 (2012)
  • Author(s): 宮尾篤欣 (大多和正樹)
  • Organizer: 第30回メディシナルケミストリーシンポジウム
  • Place of Presentation: タワーホール船堀 (東京)
• [Presentation] Atpenin A5の構造活性相関研究 (2012)
  • Author(s): 大多和正樹
  • Organizer: 第30回メディシナルケミストリーシンポジウム
  • Place of Presentation: タワーホール船堀
• [Presentation] Nafuredin-γの誘導体合成 (2012)
  • Author(s): 福永恵子、清水理紗、大多和正樹、塩見和郎、大村智、長光亨
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学札幌キャンパス
• [Presentation] Atpenin A5の構造活性相関研究 (2012)
  • Author(s): 樋浦徹、杉山晃平、大多和正樹、森美穂子、塩見和朗、大村智、長光亨
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学札幌キャンパス
• [Presentation] Atpenin A5 の構造活性相関研究 (2011)
  • Author(s): 樋浦徹 (大多和正樹)
  • Organizer: 第55回 日本薬学会関東支部大会
  • Place of Presentation: 東邦大学習志野キャンパス (千葉)
  • Year and Date: 2011-10-08
• [Presentation] ACAT2 選択的阻害剤pyripyropene A の構造活性相関研究ならびに全合成 (2011)
  • Author(s): 大多和正樹、松田大介、山崎寛之、大城太一、 大村智、長光亨、供田洋
  • Organizer: 第53回天然有機化合物討論会
  • Place of Presentation: 大阪国際交流センター
• [Presentation] Structure-activity relationship of new pyripyropene A derivatives as inhibitors of acyl-CoA:cholesterol acyltransferase 2 (2011)
  • Author(s): Ohtawa, M.;Matsuda, D.; Yamazaki H.; Ohshiro, T.; Omura, S.; Nagamitsu, T.; Tomoda, T.
  • Organizer: The 8th AFMC International Medicinal Chemistry Symposium
  • Place of Presentation: 京王プラザホテル (新宿)
• [Presentation] Atpenin A5の構造活性相関研究 (2011)
  • Author(s): 樋浦徹、大多和正樹、森美穂子、塩見和朗、大村智、長光亨
  • Organizer: 第55回日本薬学会関東支部大会
  • Place of Presentation: 東邦大学習志野キャンパス
• [Patent(Industrial Property Rights)] ACAT2阻害活性を示すピリピロペンA構造簡略型誘導体 (2013)
  • Inventor(s): 大多和正樹、大村智、供田洋、長光亨
  • Industrial Property Rights Holder: 大多和正樹、大村智、供田洋、長光亨
  • Filing Date: 2013-01-28
• [Patent(Industrial Property Rights)] ACAT2阻害活性を示す代謝酵素に安定なピリピロペン誘導体 (2011)
  • Inventor(s): 供田洋、長光亨、松田大介、大城太一、大多和正樹、大村智
  • Industrial Property Rights Holder: 供田洋、長光亨、松田大介、大城太一、大多和正樹、大村智
  • Filing Date: 2011-03-25