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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 忻凌偉(Ling-Wei Hsin) | |
| dc.contributor.author | Chu-Shan Choe | en |
| dc.contributor.author | 曹楚善 | zh_TW |
| dc.date.accessioned | 2021-06-08T01:45:12Z | - |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-15 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19104 | - |
| dc.description.abstract | To develop the 1-(2-(diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine (GBR12935) derivatives as a novel potential positron emission tomography (PET) imaging agents for dopamine transporter (DAT), a series of pyridyl-substituted derivatives was synthesized. In the series, except for the m-pyridyl substituted derivatives, all other derivatives possessed high binding affinity for DAT (Ki = 8.01–22.0 nM). The substitution of one of the phenyl ring for pyridine in GBR12935 analogs significantly reduces the lipophilicity of these compounds from log D7.4 value of 4.1 to 3.6. Introduction of fluorine atom next to the nitrogen atom in the pyridine ring, such as compounds 15a–c, increased the log D value of the compounds to 4.4. All compounds showed good blood brain barrier (BBB) penetration ability with a Pe (10-6 cm/s) values range from 31 to 89. Among this series, compound 19a showed the highest DAT binding affinity as well as appropriate lipophilicity and favorable brain penetration ability (Ki = 8.01 nM, Log D = 3.74, Pe = 62×10-6 cm/s), and is the candidate for the further development to be a novel DAT PET radiotracers. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T01:45:12Z (GMT). No. of bitstreams: 1 ntu-105-R03423025-1.pdf: 4929760 bytes, checksum: 60cb7a6b445fadf63f8eb02529479e75 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | Content ---------------------------------------------------------------------------------------------- I
中文摘要 ----------------------------------------------------------------------------------------- III Abstract ------------------------------------------------------------------------------------------- IV List of Figures ------------------------------------------------------------------------------------- V List of Tables ------------------------------------------------------------------------------------- VI List of Schemes --------------------------------------------------------------------------------- VII List of Abbreviations -------------------------------------------------------------------------- VIII Chapter 1. Introduction --------------------------------------------------------------------------- 1 1.1 The dopaminergic system --------------------------------------------------------------- 1 1.2 Dopamine transporter (DAT) ----------------------------------------------------------- 4 1.3 Molecular imaging of DAT ------------------------------------------------------------- 5 1.4 The dopamine transporter inhibitor, GRB12935 ------------------------------------ 6 1.5 Aim and objective ------------------------------------------------------------------------ 8 Chapter 2. Results and discussion -------------------------------------------------------------- 9 2.1 Chemistry -------------------------------------------------------------------------------- 9 2.1.1 Synthesis of pyridyl substituted GBR12935 derivatives ----------------- 9 2.1.2 Synthesis of fluorinated pyridyl-substituted GBR12935 derivatives ---- ----------------------------------------------------------------------------------- 13 2.2 Biological activities of target compounds ----------------------------------------- 16 2.3 Physicochemical profiles of target compounds ----------------------------------- 19 2.3.1 Partition coefficient (log P) determination -------------------------------- 21 2.3.2 Distribution coefficient (log D) determination ---------------------------- 23 2.3.3 Blood brain barrier (BBB) permeability determination ------------------ 26 Chapter 3. Conclusion -------------------------------------------------------------------------- 27 Chapter 4. References --------------------------------------------------------------------------- 28 Chapter 5. Experimental section --------------------------------------------------------------- 33 5.1 Reagents and solvents ---------------------------------------------------------------- 33 5.2 General instruments and methods --------------------------------------------------- 36 5.3 Chemical procedures ----------------------------------------------------------------- 42 Chapter 6. Appendix ---------------------------------------------------------------------------- 75 | |
| dc.language.iso | en | |
| dc.title | 吡啶基取代之1-[2-(二苯基甲氧基)乙基]-4-(3-苯丙基)哌嗪衍生物的合成及生物活性研究 | zh_TW |
| dc.title | Synthesis and Biological Activity of Pyridyl-substituted 1-[2-(Diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine Derivatives | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 王光昭(Kuang-Chao Wang),陳基旺(Ji-Wang Chern),梁碧惠(Pi-Hui Liang) | |
| dc.subject.keyword | 多巴胺轉運體,GBR12935, | zh_TW |
| dc.subject.keyword | Dopamine transporter,GBR12935, | en |
| dc.relation.page | 98 | |
| dc.identifier.doi | 10.6342/NTU201601670 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2016-08-15 | |
| 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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