臺灣博碩士論文加值系統

本篇論文主要是利用液相組合式化學合成法（liquid phase
combinatorial synthesis，LPCS），搭配微波來合成 indazole 與
tetrahydroquinazoline 的衍生物，並進行活性篩選，期望找到更具有活
性的抗癌藥物。
本篇論文分為以下幾部分:
1. 以7-(benzimidazolyl)-1,2,3,4-tetrahydroquinazoline 為骨幹，進行
官能基的修飾
2. 以6-(benzimidazolyl) -2H-indazole 為骨幹，進行官能基的修飾。
3. 液相合成methyl 2-(3,3-diphenylpropyl)-2H-indazole-6-carboxylate
4. 以7-(1H-Benzoimidazol-2-yl)-10H-benzo[4,5]imidazo[1,2-a]
[1,3,5]triazine-2,4-dione 為骨幹，進官能基修飾。

1.前言............................................................................................................................3
2.組合式化學簡介........................................................................................................4
2.1 組合式化學原理.............................................................................................4
2.2 液相組合式化學..............................................................................................7
3.微波合成技術介紹....................................................................................................9
3.1 微波合成儀器種類........................................................................................10
3.2 微波加熱的原理............................................................................................11
3.3 實驗所採用的微波裝置................................................................................13
4.研究方向..................................................................................................................15
4.1 藥物設計策略................................................................................................17
4.2 indazole 系列衍生物.....................................................................................18
5.實驗部份...................................................................................................................24
5.1 合成6-(benzimidazolyl) -2H-indazole 與
7-(benzimidazolyl)-1,2,3,4-tetrahydroquinazoline 衍生物.................24
5.1.1 利用微波進行酯化反應...................................................................24
5.1.2 利用微波進行一級胺類的芳香性取代反應...................................26
5.1.3 還原反應...........................................................................................26
5.1.4 合成起始模板...................................................................................27
5.1.5 合成起始模板...................................................................................28
5.1.6 環化..................................................................................................28
5.1.7 還原...................................................................................................29
5.1.8 第二次環化.......................................................................................31
5.1.9 將化合物切下...................................................................................31
5.4 結論...............................................................................................................36
5.5 實驗器材.......................................................................................................36
5.5.1 儀器部份..........................................................................................36
5.5.2 藥品及試劑......................................................................................37
6.參考文獻..................................................................................................................37
附錄..............................................................................................................................41
A. 活性篩選整理..............................................................................................41
抗腫瘤藥效評估..........................................................................................41
心血管作用(抗血栓藥效)評估..................................................................45
抗氣喘藥效評估..........................................................................................46

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