Characterization and application of hydrophobic functionalities bearing heavier group 14 atoms

带有较重14族原子的疏水官能团的表征和应用

• 批准号: 23790128
• 负责人: FUJII Shinya
• 金额: $ 2.83万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790128/
• 关键词: 医薬品化学; 疎水性相互作用; 有機元素化学; エストロゲン; 定量的構造活性相関; 疎水性; ケイ素; ゲルマニウム; 分配係数; 構造活性相関

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.

系统地研究了以三烷基(芳基)硅基或三烷基(芳基)Germyl为疏水取代基的简单酚类化合物的合成与表征。这些硅和锗类似物表现出比相应的碳类似物更高的疏水性，与烷基(芳基)物种无关，logP值相差约0.6。与碳类似物相比，三烷基硅基和三烷基锗基酚表现出更强的雌激素样活性。取代基参数和构效关系可能有助于利用较重的14族元素进行药物开发。

项目成果

Development of Nuclear Receptor Ligands Based on Carborane as Hydrophobic Core Structure

基于碳硼烷作为疏水核心结构的核受体配体的研制

• 发表时间: 2012
• 作者: Fujii;S.; Yamada;A.; Ohta;K.; Endo;Y.; Kagechika;H.
• 通讯作者: H.

Development and structural basis of novel non-secosteroidal VDR ligands based on hydrophobic carborane cage

基于疏水碳硼烷笼的新型非甾体VDR配体的开发和结构基础

• 发表时间: 2011
• 作者: Fujii;S.; Masuno;H.; Nakabayashi;M.; Hirano;T.; Kawachi;E.; Ito;N.; Kagechika;H.
• 通讯作者: H.

ビタミンK酸化誘導体の系統的合成とその生理活性

维生素K氧化衍生物的系统合成及其生理活性

• 发表时间: 2013
• 作者: Ikuhiko Nakase;Shinya Okumura;Sayaka Katayama;Hisaaki Hirose;Silvia Pujals;Hirofumi Yamaguchi;Satoko Arakawa;Shigeomi Shimizu;Shiroh Futaki;清水章貴
• 通讯作者: 清水章貴

Design and synthesis of novel carborane-containing AR antagonists having a grycerol moiety based on the co-crystal structure of bicalutamide with hAR LBD.

基于比卡鲁胺与 hAR LBD 的共晶结构，设计和合成具有甘油部分的新型含碳硼烷 AR 拮抗剂。

• 发表时间: 2011
• 作者: Kaise;A.;Goto;T.;Fujii;S.;Ohta;K.;Endo;Y.
• 通讯作者: Y.

p-Carborane Based AndrogenActive in LNCaP Cells with a Mutated Androgen Receptor

基于对碳硼烷的雄激素在雄激素受体突变的 LNCaP 细胞中具有活性

• DOI: 10.1039/c1md00001b
• 发表时间: 2011
• 期刊: Med. Chem. Commun
• 作者: Shinya Fujii;Ayumi Yamada;Keiko Tomita;Mao Nagano;Tokuhito Goto;Kiminori Ohta;Takashi Harayama;Yasuyuki Endo;Hiroyuki Kagechika
• 通讯作者: Hiroyuki Kagechika