Characterization and application of hydrophobic functionalities bearing heavier group 14 atoms

2012 Fiscal Year Final Research Report

• Project/Area Number: 23790128
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: FUJII Shinya 東京医科歯科大学, 生体材料工学研究所, 助教 (60389179)
• Project Period (FY): 2011 – 2012
• Keywords: 医薬品化学

Research Abstract

Systematic synthesis and characterization of simple phenols bearing a trialkyl(aryl)silyl or trialkyl(aryl)germyl functional group as a hydrophobic substituent were investigated. These silicon and germanium analogs exhibited higher hydrophobicity than the corresponding carbon analogs, with a difference in logP value of approximately 0.6, independent of the alkyl(aryl) species. The trialkylsilyl- and trialkylgermylphenols exhibited more potent estrogenic activity as compared with the carbon analogs. The substituent parameters and structure-activity relationship may be helpful for drug discovery utilizing the heavier group 14 elements.

Research Products

• [Journal Article] Increased hydrophobicity and estrogenic activity of simple phenols with silicon and germanium-containing substituents. (2013)
  • Author(s): Fujii, S.; Miyajima, Y.; Masuno, H.; Kagechika, H.
  • Journal Title: J. Med. Chem. Volume: 56 Pages: 160-166
  • DOI: DOI:10.1021/jm3013757
• [Journal Article] Development of androgen receptor ligands by application of ten-vertex para-carborane as a novel hydrophobic core structure (2012)
  • Author(s): Fujii, S.; Ohta, K.; Goto, T.; Oda, A.; Masuno, H.; Endo, Y.; Kagechika, H.
  • Journal Title: Med. Chem. Commun. Volume: 3 Pages: 680-684
  • DOI: DOI:10.1039/C2MD00294A
• [Journal Article] Boron cluster-based development of potent nonsecosteroidal vitamin D receptor ligands: Direct observation of hydrophobic interaction between protein surface and carborane (2011)
  • Author(s): Fujii, S.; Masuno, H.; Taoda, Y.; Kano, A.; Wongmayura, A.; Nakabayashi, M.; Ito, N.; Shimizu, M.; Kawachi, E.; Hirano, T.; Endo, Y.; Tanatani, A.; Kagechika, H.
  • Journal Title: J. Am. Chem. Soc. Volume: 133 Pages: 20933-20941
  • DOI: DOI:10.1021/ja208797n
• [Presentation] シリル基・ゲルミル基の疎水性基としての性質と新規エストロゲン受容体リガンド創製への応用 (2013)
  • Author(s): 藤井晋也,宮島友,増野弘幸,影近弘之.
  • Organizer: 日本薬学会133年会
  • Place of Presentation: 横浜
  • Year and Date: 20130300
• [Presentation] シリル基・ゲルミル基の疎水性基としての性質と新規エストロゲン受容体リガンドの創製 (2012)
  • Author(s): 藤井晋也,宮島友,増野弘幸,影近弘之.
  • Organizer: 日本レチノイド研究会第23回学術集会
  • Place of Presentation: 米子
  • Year and Date: 20121000
• [Presentation] Hydrophobic parameters, substituent constants and estrogenic activities of silyl- and germyl-containing phenols (2012)
  • Author(s): Fujii, S.; Miyajima, Y.; Masuno, H.; Kagechika, H.
  • Organizer: ISMC2012 International Symposium of Medicinal Chemistry 2012
  • Place of Presentation: ベルリン(ドイツ).
  • Year and Date: 20120900
• [Presentation] トリアルキルシリルおよびゲルミル基の性質と生理活性物質の疎水性構造への応用 (2012)
  • Author(s): 藤井晋也,宮島友,増野弘幸,影近弘之.
  • Organizer: 日本ケミカルバイオロジー研究会第7回年会
  • Place of Presentation: 京都
  • Year and Date: 20120600
• [Presentation] Development of Nuclear Receptor Ligands Based on Carborane as Hydrophobic Core Structure (2012)
  • Author(s): Fujii, S.; Yamada, A.; Ohta, K.; Endo, Y.; Kagechika, H.
  • Organizer: The 1st HD Physiology International Symposium
  • Place of Presentation: 東京
  • Year and Date: 20120100
• [Presentation] Development and structural basis of novel non-secosteroidal VDR ligands based on hydrophobic carborane cage (2011)
  • Author(s): Fujii, S.; Masuno, H.; Nakabayashi, M.; Hirano, T.; Kawachi, E.; Ito, N.; Kagechika, H.
  • Organizer: IME Boron XIV 14th International Meeting on Boron Chemistry
  • Place of Presentation: ナイアガラフォールズ(カナダ)
  • Year and Date: 20110900
• [Remarks]
  • URL: http://www.tmd.ac.jp/mri/omc/index1.html