臺灣博碩士論文加值系統

一系列含肟的3,4-二氫喹啉酮衍生物已被合成並且也評估它們的抗血小板及抗細胞增生的活性。這些化合物的合成是經由芳香氫氧基的烷化作用，再與氫氧化胺進行親核性加成反應。
予試驗活性分析中得知，(Z)-7-(2-(4-fluorophenyl)-2-
(hydroxyimino)ethoxy)-3,4-dihydroquinolin-2(1H)-one(11d)對以U46619誘導劑時所產生的血小板凝集有最好的抑制活性，其IC50值為3.51μM；而對於花生四烯酸所誘導的凝集作用，則以(E)-6-(2-(hydroxyimino)propoxy)-3,4-dihydroquinolin-2(1H)-one (6a) 具有最佳的抑制效果，其IC50值為1.85 μM；含肟的3,4-二氫喹啉酮衍生物對於凝血酶為誘導劑時所誘導的血小板凝集，則無顯著的抑制活性，其IC50值均高於26.78 μM。在抗細胞增生方面，大部份的含肟的3,4-二氫喹啉酮衍生物並無明顯的抑制活性，只有衍生物(Z)-7-(2-(hydroxyimino)-2-(naphthalen-2-yl)ethoxy)-3,4-dihydroquinolin-2(1H)-one (11b) 表現出對於鼻咽癌、非小細胞肺癌及血癌細胞的增生具有抑制作用，其IC50值分別為7.63,、7.34及6.36 μM。

Certain oxime-containing 3,4-dihydroquinolin-2(1H)-one derivatives
were synthesized and evaluated for their antiplatelet and antiproliferative
activities. These compounds were synthesized via alkylation of hydroxyl precursors followed by the reaction with NH2OH .
The preliminary assays indicated that (Z)-7-(2-(4-fluorophenyl)-2-(h
ydroxyimino)ethoxy)-3,4-dihydroquinolin-2(1H)-one (13c) was the most
active against U46619 induced platelet aggregation with an IC50 value of 3.51 μM. For the inhibition of AA-induced aggregation, (E)-6-(2-(hydrox
yimino)propoxy)-3,4-dihydroquinolin-2(1H)-one (15) was the most potent
with an IC50 value of 1.85 μM. These oxime-containing 3,4-dihydroquino
lin-2(1H)-one derivatives were inactive against thrombin induced platelet
aggregation with an IC50 value of greater than 26.78 μM. For the
antiproliferative activity, most of these oxime-containing 3,4-dihydroquin
olin-2(1H)-one derivatives were inactive while (Z)-7-(2-(hydroxyimino)-
2-(naphthalen-2-yl)ethoxy)-3,4-dihydroquinolin-2(1H)-one (13a)
exhibited only marginal activities with IC50 value of 7.63, 7.34 and 6.36
μM against the growth of NPC-TW01, H-661, and Jurkat respectively.

目 錄
中文摘要……………………………………………………………………Ⅰ
英文摘要……………………………………………………………………Ⅱ
誌謝…………………………………………………………………………………Ⅲ
目錄…………………………………………………………………………Ⅳ
圖目錄………………………………………………………………………Ⅵ
表目錄………………………………………………………………………Ⅶ

第一章 緒論…………………………………………………………………1
第一節 前言…………………………………………………………………1
第二節 研究動機與目的……………………………………………………9
第二章 合成方法與步驟…………………………………………………14
第一節 合成大綱…………………………………………………………14
第二節 合成步驟與方法…………………………………………………16
一、6位含肟之3,4-二氫喹啉酮衍生物6 a-f的合成……………………16
二、7位含肟之3,4-二氫喹啉酮衍生物11 a-f的合成………………19
三、8位含肟之3,4-二氫喹啉酮衍生物16 a-f的合成………………21
第三章 生物活性評估……………………………………………………23
第一節 抗血小板凝集活性試驗…………………………………………23
ㄧ、實驗方法………………………………………………………………23
二、結果與討論………………………………………………………………25
第二節 細胞毒活性試驗…………………………………………………30
ㄧ、實驗方法………………………………………………………………30
二、結果與討論………………………………………………………………31
第四章 實驗部份…………………………………………………………34
第一節 儀器與試藥………………………………………………………34
一、儀器……………………………………………………………………34
二、試藥……………………………………………………………………35
第二節 各化合物的製備…………………………………………………36
ㄧ、6-位含肟之3,4-二氫喹啉酮衍生物的製備(6 a-f) …………………36
二、7-位含肟之3,4-二氫喹啉酮衍生物的製備(11 a-f)…………………42
三、8-位含肟之3,4-二氫喹啉酮衍生物的製備(16 a-f)…………………48
第五章 總結……………………………………………………………………54
參考文獻……………………………………………………………………57

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