Medicinal chemical study by the three-dimensional structural diversity-oriented strategy based on the characteristic steric and stereoelectronic features of cyclopropane

2015 Fiscal Year Final Research Report

• Project/Area Number: 24390023
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• 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): FUKUDA Hayato 北海道大学, 大学院薬学研究院, 助教 (30434450)
• Co-Investigator(Renkei-kenkyūsha): MINAMI Masabumi 北海道大学, 大学院薬学研究院, 教授 (20243040) ; HIGASHIDA Haruhiro 金沢大学, 子どものこころの発達研究センター, 特任教授 (30093066) ; HIROKAWA Takatugu 国立研究開発法人産業技術総合研究所, 創薬分子プロファイリング研究センター, 分子シミュレーションチームチーム長 (20357867)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: シクロプロパン / 配座制御 / 三次元的多様性 / 分子設計 / BGT-1 阻害剤 / プロテアソーム阻害剤 / BASE阻害剤

Outline of Final Research Achievements

Cyclopropane is very effective for conformational restriction of compounds due to the characteristic steric and stereoelectronic features, which are sic/trans-restriction, cyclopropylic strain, and bisected conformational preference. We devised the three-dimensional structural diversity-oriented conformational restriction strategy based on the characteristic features of cyclopropane, by which a variety of conformationally restricted analogs of conformationally flexible biologically active prototype compounds were designed and synthesized. Thus, we successfully identified highly potent compounds, which are a GABA transporter subtype BGT-1 inhibitor, proteasome inhibitors, and β-secretase (BASE) inhibitors.

Free Research Field

創薬化学