Development research into obesity improvement medicine

• Project/Area Number: 18590109
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Hoshi University
• Principal Investigator: HIGASHIYAMA Kimio Hoshi University, 薬学部, 教授 (70101582)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥2,690,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
• Keywords: 肥満 / 糖尿病 / 血糖降下作用 / 抗酸化作用 / 血糖効果作用

Research Abstract

本研究は、血糖降下作用と抗酸化作用を同時に有した糖尿病治療薬にも繋がる、肥満改善薬の開発を目指したものである。血糖降下作用部位としてmetforminの有するビグアニジル基に着目し、これに抗酸化作用部位を結合した様々な化合物を合成して血糖降下作用を調べた。その結果、合成抗酸化剤として使用実績のあるブチルヒドロキシアニソールに2個のメチレン鎖を隔ててビグアニジル基を導入した化合物に極めて強力な血糖降下作用があることを見出した。

Research Products

• [Journal Article] Concise Total Synthesis of (-)-Deoxocuscohygrine and (-)-Dihydrocuscohygrine (2008)
  • Author(s): T. Yamauchi, S. Hagiwara, and K. Higashiyama
  • Journal Title: J. Org. Chem 73 (24) Pages: 9784-9787
  • Peer Reviewed
• [Journal Article] p-Dodecylaminophenol derived from the synthetic retinoid, fenretinide : antitumor efficacy in vitro and in vivo against human prostate cancer and mechanism of action (2008)
  • Author(s): N. Takahashi
  • Journal Title: Int. J. Cancer 122 Pages: 689-698
  • Peer Reviewed
• [Journal Article] Concise Total Synthesis of (-)-Deoxocuscohygrine and (-)-Dihydrocuscohygrine (2008)
  • Author(s): T. Yamauchi
  • Journal Title: J. Org. Chem 73 Pages: 9784-9787
  • Peer Reviewed
• [Journal Article] Changes in the rewarding effects induced by tramadol and its active metabolite M1 after sciatic nerve injury in mice (2008)
  • Author(s): A. Nakamura
  • Journal Title: Psychopharmacology 200 Pages: 307-316
  • Peer Reviewed
• [Journal Article] Potent anticancer activities of novel aminophenol analogues against various cancer cell lines (2007)
  • Author(s): T.Ohba
  • Journal Title: Bioorganic & Medicinal Chemistry 15 Pages: 847-853
  • Peer Reviewed
• [Journal Article] Stmcture modification of andrographolide to improve its potency as anticancer (2007)
  • Author(s): H.Powerono
  • Journal Title: Indo.J.Chem 7 Pages: 202-207
  • Peer Reviewed
• [Journal Article] Lack of development of behavioral sensitization to methylphenidate in mice:Correlation with reversible astrocytic activation (2007)
  • Author(s): T.Suzuki
  • Journal Title: Eur.J.Pharmacol 574 Pages: 39-48
  • Peer Reviewed
• [Journal Article] Hypoglycemic effects of multiflorine derivatives in normal mice (2006)
  • Author(s): H. Kubo, M. Inoue, J. Kamei, and K. Higashiyama
  • Journal Title: Biol. Pharm. Bull 29, (10) Pages: 2046-50
  • NAID: 110004810290
  • Peer Reviewed
• [Journal Article] Hypoglycemic effects of multiflorine derivas in normal mice. (2006)
  • Author(s): Hajime Kubo
  • Journal Title: Biol. Pharm. Bull. 29・10 Pages: 5-5
• [Journal Article] Potent anticancer activities of novel aminophenol analogues against various cancer cell lines. (2006)
  • Author(s): Noriko Takahashi
  • Journal Title: Bioorganic ＆ Medicinal Chemistry, 14・17 Pages: 8-8
• [Presentation] Matrine型アルカロイドの構造活性相関 Part16 ; 光学活性3-Benzylpiperidine誘導体の抗侵害作用 (2008)
  • Author(s): 山内 貴靖
  • Organizer: メディシナルケミストリーシンポジウム
  • Place of Presentation: 大阪
• [Presentation] ビグアニジン化合物の合成と血糖降下作用 (2007)
  • Author(s): 久保元, 東山公男
  • Organizer: 日本薬学会第127年会
  • Place of Presentation: 富山
• [Presentation] Hypoglycemic effects of metformin derivatives in normal mice (2007)
  • Author(s): H. Kubo, and K. Higashiyama
  • Organizer: 21th International Congress for Heterocyclic Chemistry
  • Place of Presentation: Sydney, Australia
• [Presentation] Hypoglycemic Effects of Metformin Derivatives in Normal Mice (2007)
  • Author(s): K.Higashiyama
  • Organizer: 国際複素環学会
  • Place of Presentation: Sydney,Australia
• [Presentation] ビスグアニジル化合物の合成と血糖降下作用 (2006)
  • Author(s): 久保元, 鎌田勝雄, 東山公男
  • Organizer: 日本薬学会第126年会
  • Place of Presentation: 仙台