請用此 Handle URI 來引用此文件：
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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 忻凌偉(Ling-Wei Hsin) | |
| dc.contributor.author | Wei-Han Chen | en |
| dc.contributor.author | 陳韋涵 | zh_TW |
| dc.date.accessioned | 2021-06-07T17:54:50Z | - |
| dc.date.copyright | 2012-09-19 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-16 | |
| dc.identifier.citation | 1. Pimlott, S. L.; Sutherland, A. Molecular Tracers for the PET and SPECT Imaging of Disease. Chem. Soc. Rev., 2011, 40, 149–162
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/15898 | - |
| dc.description.abstract | 本研究目的為發展有潛力具選擇性之 5-HT7 受體配體，並且應用於正子掃描影像劑。根據過去本實驗室設計合成的幾個系列化合物藥理活性之結果， 6-Methoxy-8-(2-methoxyphenyl)-1,2,3,4-tetrahydroisoquinolin-7-ol 被選定為核心結構。在這項研究中，一套有效的硝化方法被發展出來，且合成了了一系列的硝基和硝基-氟取代丙基苯的合成子；並且藉 GC 分析硝化反應的位向選擇性。此外，優化的還原法也被建立，製備了不同的溴-取代丙基苯合成子。這些合成子被用於合成一系列新穎的衍生物；其中，硝基-取代之化合物 11 (Ki = 2.78 nM)，14 (Ki = 3.60 nM)，16 (Ki = 6.04 nM)，展現了顯著的 5-HT7 受體的結合親合力，極有潛力作為5-HT7 受體之 18F 標定的正子斷層影像劑前驅物。最後，以氟離子芳香環親核性取代反應之模型研究，為未來使用 18F 製備正子斷層掃描影像劑，提供了有價值的參考資訊。 | zh_TW |
| dc.description.abstract | Based on the preliminary pharmacological data of several series of compounds synthesized in our laboratory, 6-methoxy-8-(2-methoxyphenyl)-1,2,3,4-
tetrahydroisoquinolin-7-ol was chosen as the core structure for the development of selective 5-HT7 receptor ligands as potential positron emission tomography (PET) imaging agents for 5-HT7 receptor. In this study, an efficient nitration method was developed for the preparation of a series of nitro and nitro-fluoro-substituted propylbenzene synthons, and the regioselectivities of nitration reactions were determined by GC. In addition, optimization of the reduction reaction conditions was conducted to prepare various bromo-substituted propylbenzene synthons. The nitro-substituted compounds 11 (Ki = 2.78 nM), 14 (Ki = 3.60 nM), 16 (Ki = 6.04 nM) with profound 5-HT7 receptor binding affinity are promising to be potential precursors for the development of 18F-labeled PET imaging agents. Model study of aromatic nucleophilic substitution using fluoride was conducted, which provided valuable information for preparation of PET imaging agents using [18F]-fluoride in the future. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-07T17:54:50Z (GMT). No. of bitstreams: 1 ntu-101-R99423023-1.pdf: 7283824 bytes, checksum: 6e8d9a8ac97819ed81326fc45f237712 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 口委審定書 I
誌謝 II 摘要 III Abstract IV 英文縮寫表 V 圖目錄 X 表目錄 X 路徑目錄 XI 緒論 1 1.1 正子斷層掃描 PET 原理及其應用 1 1.2 正子斷層掃描顯影劑之放射化學 (radiochemistry) 3 1.3.1 以 5-HT7 受體為研究目標 4 1.3.2 化合物結構設計的理論根據 5 研究目的 7 結果與討論 8 第一階段目標化合物之設計合成 8 1.1 目標化合物之選定 8 1.2 合成路徑設計概念 8 1.3.1 嘗試用 N-demethylation 得到核心結構 10 1.3.2 利用市售的起始物合成 N-Troc 保護的中間體 11 1.3.3 以O-Benzyl 保護的中間體合成 N-Troc 中間體 12 1.3.4 合成關鍵中間體 17 最後步驟 13 1.4 側鏈設計與製備 15 1.4.1氟取代苯環之側鏈製備 15 1.5 溴取代之側鏈製備 16 1.5.1 側鏈 34 之合成研究 16 1.5.2 側鏈35 之合成研究 18 1.5.3 側鏈36 之合成研究 19 1.6氟化反應製備側鏈方法 20 1.7.1 利用關鍵中間體 17為起始物合成目標化合物 20 1.7.2 利用丙烯溴側鏈合成目標化合物之研究分析 21 第二階段目標化合物之設計合成 22 2.1 結構設計之理論根據 22 2.2目標化合物之選定 22 2.3 側鏈設計與製備 23 2.3.1 建立硝化反應條件並合成側鏈 24 2.3.2 雙硝基取代側鏈 56 之合成研究 25 2.3.3 氟硝基取代側鏈之合成研究 26 2.4 第二階段目標化合物之合成 28 2.4.1利用三氟乙酸催化合成目標化合物11 28 2.4.2利用關鍵中間體 17 合成第二階段目標化合物 28 第三階段之微量模型研究 30 3 研究目標 30 藥理活性 33 結論 34 Experimental Sections 36 1. Reagents and solvents resources 36 1.1. Commercial reagents and solvents 36 1.2 Anhydrous solvents 38 1.3 Rapid purifications of reagents 38 2. Instrumental analysis devices and methods 39 附圖目錄 87 附表目錄 88 圖譜目錄 88 | |
| dc.language.iso | zh-TW | |
| dc.subject | 微波輔助加熱反應 | zh_TW |
| dc.subject | 血清素受體 | zh_TW |
| dc.subject | 正子斷層掃描 | zh_TW |
| dc.subject | 影像劑 | zh_TW |
| dc.subject | 芳香環親核性取代反應 | zh_TW |
| dc.subject | aromatic nucleophilic substituton | en |
| dc.subject | microwave-assited heating reaction | en |
| dc.subject | 5-HT7 Receptor | en |
| dc.subject | Positron Emission Tomography | en |
| dc.subject | Imaging Agents | en |
| dc.title | 合成新穎5-HT7受體配體作為有潛力之正子斷層掃描影像劑 | zh_TW |
| dc.title | Synthesis of Novel 5-HT7 Receptor Ligands as Potential Positron Emission Tomography Imaging Agents | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 王光昭,顧記華,梁碧惠 | |
| dc.subject.keyword | 血清素受體,正子斷層掃描,影像劑,芳香環親核性取代反應,微波輔助加熱反應, | zh_TW |
| dc.subject.keyword | 5-HT7 Receptor,Positron Emission Tomography,Imaging Agents,aromatic nucleophilic substituton,microwave-assited heating reaction, | en |
| dc.relation.page | 129 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2012-08-16 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| 顯示於系所單位： | 藥學系 | |
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