Development and Application of Novel 3-Dimensional Hydrophobic Structures for Drug Design, Which Are Focused on Molecular Recognition between Ligand and Receptor
药物设计中新型三维疏水结构的开发和应用,重点关注配体和受体之间的分子识别
基本信息
- 批准号:16390032
- 负责人:
- 金额:$ 9.66万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2004
- 资助国家:日本
- 起止时间:2004 至 2007
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Carboranes (dicarba-closo-dodecaboranes) are a class of carbon-containing polyhedral boron-cluster compounds having globular shape, remarkable thermal stability and hydrophobic character. In this study, we applied their molecular shape and hydrophobic surface of the molecules to design and synthesis of nuclear receptor ligands. Hydrophobic and hydrogen bonding interaction of carborane derivatives, and synthetic methods of carborane derivatives for analysis and preparation of various carborane-containing compounds were also investigated. The results were summarized as follows.1. Candidate estrogen receptor ligands with two phenolic residues on a 3-dimensional hydrophobic core structure (carborane, bicyclo[2, 2, 2]octane, adamantane) were synthesized and biologically evaluated. Amog the carborane-containing compounds, a dynamic change of agonist/antagonist balance was observed depending on the direction and the distance of the two phenolic groups.2. Candidate androgen receptor ligands bearing carborane as a hydrophobic pharmacophore were designed based on testosterone and aromatic anti-estrogen agents, and synthesized, biologically evaluated. Novel potent non-steroidal androgen antagonists BA321, BA341 were found.3. Intramolecular hydrogen bonding on 2-(2-hydroxyphenyl)-o-carborane and 2-(2-hydroxyphenyl)-p-carborane were observed on H-NMR study. The intranolecular hydrogen bonding was confirmed by X-ray, IR and DFT calculation.4. A few synthetic method of carborane derivatives, such as regioselective iodination reaction on the carborane cage, facile hydroxylation of a carbon on, the carborane cage were developed.
碳硼烷(二碳-近十二硼烷)是一类具有球形、优异的热稳定性和疏水性的含碳多面体硼簇化合物。在这项研究中,我们利用它们的分子形状和疏水表面来设计和合成核受体配体。研究了碳硼烷衍生物的疏水和氢键相互作用,以及碳硼烷衍生物的合成方法,用于分析和制备各种含碳硼烷化合物。结果总结如下:1。合成了在三维疏水核心结构上具有两个酚基残基的候选雌激素受体配体(碳硼烷、双环[2,2,2]辛烷、金刚烷)并进行了生物学评价。在含碳硼烷的化合物中,根据两个酚基的方向和距离,观察到激动剂/拮抗剂平衡的动态变化。以睾酮和芳香族抗雌激素药物为基础,设计了以碳硼烷为疏水药效团的候选雄激素受体配体,并进行了合成和生物学评价。发现了新型强效非甾体雄激素拮抗剂BA321、BA341。H-NMR研究了2-(2-羟基苯基)-o-碳硼烷和2-(2-羟基苯基)-对碳硼烷分子内氢键的形成。通过x射线、红外光谱和DFT计算证实了分子内氢键的存在。发展了几种碳硼烷衍生物的合成方法,如碳硼烷笼上的区域选择性碘化反应、碳上的易羟基化反应、碳硼烷笼。
项目成果
期刊论文数量(133)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
創薬化学における新規3次元的疎水性構造単位の開発と応用
新型三维疏水结构单元在药物化学中的开发及应用
- DOI:
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Kato Y;Watanabe C;Tsuji A;武田厚司;Takashi Nagamine;武田厚司;Tsuji A;遠藤 泰之
- 通讯作者:遠藤 泰之
Novel Retinoid X Receptor(RXR) Antagonists Having a Dicarba-closo-dodecaborane as a Hydrophobic Moiety
具有双卡-氯-十二硼烷作为疏水部分的新型视黄醇 X 受体 (RXR) 拮抗剂
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:Ohta;K.;Iijima;T.;Kawachi;E.;Kagechika;H.;Endo;Y*
- 通讯作者:Y*
A New Application of Inorganic Cluster, Carboranes for Medicinal Drug Design and Molecular Construction
无机簇碳硼烷在药物设计和分子构建中的新应用
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:Endo;Y.*;Ohta;K.;Yoshimi;T.;Yamaguchi;K
- 通讯作者:K
カルボラン環B-アリール化反応と機能性分子構築への応用
碳硼烷环B-芳基化反应及其在功能分子构建中的应用
- DOI:
- 发表时间:2008
- 期刊:
- 影响因子:0
- 作者:久保義行;杉本宏史;加藤将夫;辻彰;遠藤 泰之;相澤 光栄;千葉 由紀;小川 卓巳;相澤 光栄
- 通讯作者:相澤 光栄
カルボランC-H水素の相互作用を利用したホスト分子の構築
利用碳硼烷 C-H 氢相互作用构建主体分子
- DOI:
- 发表时间:2008
- 期刊:
- 影响因子:0
- 作者:久保義行;杉本宏史;加藤将夫;辻彰;遠藤 泰之;相澤 光栄;千葉 由紀;小川 卓巳;相澤 光栄;山崎 広人
- 通讯作者:山崎 広人
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
ENDO Yasuyuki其他文献
ENDO Yasuyuki的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('ENDO Yasuyuki', 18)}}的其他基金
A New Development of Molecular Design Utilizing Novel Hydrophobic Structures
利用新型疏水结构的分子设计新进展
- 批准号:
26460151 - 财政年份:2014
- 资助金额:
$ 9.66万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Epidemiological survey for canine tick-borne diseases in Japan
日本犬蜱传疾病流行病学调查
- 批准号:
23580442 - 财政年份:2011
- 资助金额:
$ 9.66万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of Receptor Regulators Utilizing Novel HydrophobicStructure and Its Application for Medicinal Drug Design
利用新型疏水结构开发受体调节剂及其在药物设计中的应用
- 批准号:
20390035 - 财政年份:2008
- 资助金额:
$ 9.66万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Study on Electronic and Steric Effects of Boron Cluster and Application for Construction of Functional Molecules.
硼团簇的电子和空间效应研究及其在功能分子构建中的应用。
- 批准号:
13470468 - 财政年份:2001
- 资助金额:
$ 9.66万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Design and Synthesis of Cellular Signal Transduction Modulator, Benzolactam Derivatives and Related Compounds
细胞信号转导调节剂、苯并内酰胺衍生物及相关化合物的设计与合成
- 批准号:
10470463 - 财政年份:1998
- 资助金额:
$ 9.66万 - 项目类别:
Grant-in-Aid for Scientific Research (B).
Design, Synthesis and Biological Activity of Anti-HIV Compounds Derived from Teleocidins
Teleocidins 抗 HIV 化合物的设计、合成和生物活性
- 批准号:
07557377 - 财政年份:1995
- 资助金额:
$ 9.66万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Search for New Tumor Promoters Employing Chemical Calculation
利用化学计算寻找新的肿瘤促进剂
- 批准号:
04671288 - 财政年份:1992
- 资助金额:
$ 9.66万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
相似海外基金
Molecular basis of activation of the orphan nuclear receptor Nurr1
孤儿核受体 Nurr1 激活的分子基础
- 批准号:
10831795 - 财政年份:2023
- 资助金额:
$ 9.66万 - 项目类别:
Nuclear Receptor Networks in Mucosal Immune Regulation
粘膜免疫调节中的核受体网络
- 批准号:
10822885 - 财政年份:2023
- 资助金额:
$ 9.66万 - 项目类别:
Mechanisms by which histone methyltransferases regulate nuclear receptor activity and response to therapy in hormone-driven tumors.
组蛋白甲基转移酶调节核受体活性和激素驱动肿瘤治疗反应的机制。
- 批准号:
10563751 - 财政年份:2023
- 资助金额:
$ 9.66万 - 项目类别:
Regulation of tissue stem cell lineages by nuclear receptor signaling
通过核受体信号传导调节组织干细胞谱系
- 批准号:
10710837 - 财政年份:2023
- 资助金额:
$ 9.66万 - 项目类别:
Molecular mechanism of PIN1-mediated regulation of the nuclear receptor PPARy
PIN1介导的核受体PPARγ调节的分子机制
- 批准号:
10607310 - 财政年份:2023
- 资助金额:
$ 9.66万 - 项目类别:
Nuclear receptor regulation of epigenetic mechanisms regulating HIV CNS latency
表观遗传机制的核受体调节调节HIV中枢神经系统潜伏期
- 批准号:
10747002 - 财政年份:2023
- 资助金额:
$ 9.66万 - 项目类别:
Ligand-dependent regulation of the nuclear receptor REV-ERBa in TH17 cell development and inflammation
TH17 细胞发育和炎症中核受体 REV-ERBa 的配体依赖性调节
- 批准号:
10608664 - 财政年份:2023
- 资助金额:
$ 9.66万 - 项目类别:
Nuclear Receptor Dysfunction Reprograms Metabolism and Cellular Proliferation in Wilson's Disease
威尔逊病中核受体功能障碍重新编程代谢和细胞增殖
- 批准号:
10516671 - 财政年份:2022
- 资助金额:
$ 9.66万 - 项目类别:
Regulation of Nuclear Receptor Expression and Function
核受体表达和功能的调节
- 批准号:
RGPIN-2019-05254 - 财政年份:2022
- 资助金额:
$ 9.66万 - 项目类别:
Discovery Grants Program - Individual
The role of a novel SUMO conjugation process on nuclear receptor function and gene transcription
新型相扑缀合过程对核受体功能和基因转录的作用
- 批准号:
RGPIN-2019-05580 - 财政年份:2022
- 资助金额:
$ 9.66万 - 项目类别:
Discovery Grants Program - Individual