請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17325
標題: | 合成8-苯基異喹啉衍生物作為有潛力之5-HT7受體正子斷層掃描追蹤劑 Synthesis of 8-Phenylisoquinolines as Potential Positron Emission Tomography Imaging Agents for 5-HT7 Receptor |
作者: | Yi-Jing Wang 王怡菁 |
指導教授: | 忻凌偉(Ling-Wei Hsin) |
關鍵字: | 8-苯基異??,5-HT7受體,正子斷層掃描, 8-Phenylisoquinolines,Positron Emission Tomography,5-HT7 Receptor, |
出版年 : | 2013 |
學位: | 碩士 |
摘要: | 5-HT7受體在人體中扮演著重要角色,認為與多種CNS的功能息息相關,例如:體溫調節、晝夜節律、學習、記憶、睡眠及憂鬱等,若是能了解5-HT7受體與各種相關疾病之間的關係,那麼將能進一步探討疾病成因及病理機轉。正子斷層掃描(Possitron Emission Tomography, PET)有較佳的靈敏度及空間解析度已被廣泛應用於診斷癌症、心臟病、神經退化及精神疾病。其中5-HT1A及5HT2A兩種亞型之正子造影劑已經發展出來,本研究為發展具高親和力與選擇性之5-HT7受體配體做為有潛力之正子掃描造影劑,以6-methoxy-8-(2-methoxyphenyl)-1,2,3,4-
tetrahydroisoquinolin-7-ol為核心結構,在氮的位置上以雙鹵素取代之苯乙基側鏈與苯磺醯胺官能基及不同長度之碳鏈(n = 3-5)修飾取代以形成一系列衍生物。經過生物活性及脂溶性評估,發現化合物27 (Ki = 1.62 nM) 展現了高度的5-HT7受體之親和力及脂溶性,極有潛力作為5-HT7受體之18F標定正子斷層造影劑。硝基衍生物32與38也被合成作為日後18F放射標定所需之前驅物。 The 5-HT7 is considered to be closely related to various functions of CNS such as thermoregulation, circadian rhythm, learning, memory, sleep and depression. Exploring the important role of 5-HT7 receptor in human body will give us in sight of the etiology and pathophysiology of related diseases. Positron emission tomography (PET) has high sensitivity and spatial resolution in the molecular imaging and it is used in the diagnosis of cancer, heart disease, neurological and neurodegenerative disease. The PET imaging agents of the 5-HT1A and 5HT2A have been developed. Therefore, for the development of high affinity and selective 5-HT7 receptor ligands as potential positron emission tomography imaging agents for 5-HT7 receptor, we chose 6-methoxy-8-(2-methoxyphenyl)-1,2,3,4-tetrahydroisoquinolin-7-ol as the core structure, and modified the amino group of the core structure with dihalide substituted phenyl group and phenylsulfonamide alkyl side chains. According to the binding affinity data and distribution coefficient data, the compound 27 shows high 5-HT7 receptor affinity (Ki = 1.62 nM) and ideal log D to be a potential 18F-labeled PET imaging agent for 5-HT7 receptor. The nitro-substituted precursor 32 and 38 were also synthesized as precursor of 18F-labeled PET imaging agent. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17325 |
全文授權: | 未授權 |
顯示於系所單位: | 藥學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-102-1.pdf 目前未授權公開取用 | 6.94 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。