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研究生:賴玉琪
論文名稱:(2E)-3-[2-(取代芐氧基)-4(或5)甲氧基苯基]丙烯醛及其衍生物之合成及生物活性
論文名稱(外文):Synthesis and biological activities of (2E)-3-[2-(substituted benzyloxy0-4(or 5) methoxyphenyl] acrylaldehyde derivatives
指導教授:郭盛助郭盛助引用關係黃麗嬌黃麗嬌引用關係
學位類別:碩士
校院名稱:中國醫藥學院
系所名稱:藥物化學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2003
畢業學年度:91
語文別:中文
中文關鍵詞:丙烯醛
相關次數:
  • 被引用被引用:1
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為了得到強力的抗發炎、抗過敏、抗癌細胞增生之新型先導化合物,著者設計(2E)-3-[2-(substituted-benzyloxy)-4(or 5)methoxyphenyl] acrylaldehyde及其相關化合物做為標的化合物。
主要中間體 2-(benzyloxy)-5-methoxybenzaldehyde (22-42)是由 2-hydroxy-4(or 5)methoxybenzaldehyde 在無水碳酸鉀、碘化鉀存在下,與 substituted benzyl chloride 加熱迴流而得;而其中一類的標的化合物 (2E)-3-{2-
[(substituted-benzyl)oxy]phenyl}acrylaldehyde (44-60) 則是利用2-hydroxy-
cinnamaldehyde 在無水碳酸鉀、碘化鉀存在下,與 substituted benzyl chloride 加熱迴流而得;而另一類的標的化合物 (2E)-3-{2-[(Substituted-benzyl)oxy]- 5-methoxyphenyl}acrylaldehyde (63-80) 則是利用化合物 22-42 在零度C、NaOH 條件下,與 acetaldehyde 經 aldol-condensation 反應而成。
將所合成的標的化合物及其中間體進行抗發炎、抗過敏、抑制癌細胞增殖活性之評估,並初步進行其結構與活性之關係。
這些化合物中,以具有 acrylaldehyde (-CH=CHCHO)之衍生物(44-60,63-79)對於抗發炎、抗過敏及抑制癌細胞增殖的活性均較為顯著;其中(2E)-3-[2-(benzyloxy)-5-methoxyphenyl]acrylaldehyde (63),(2E)-3-{2-[(4-chloro-
benzyl)oxy]-5-methoxyphenyl}acrylaldehyde (66),(2E)-3-{2-[(3,5-difluorobenzyl)- oxy]-5-methoxyphenyl}acrylaldehyde (77)為最具潛力的物質,可作為開發新型抗發炎、抗過敏藥物之基本架構;(2E)-3-{2-[(4-methoxybenzyl)oxy]phenyl}- acrylaldehyde (50)針對抑制 HL-60、U937 等血癌細胞株的增生效果最佳,可對此進一步探討其作用機轉,而作為開發新型抗癌藥物的基本架構。
第一章 緒論
第一節 嗜中性白血球與肥大細胞之生理功能…………………………...1
第二節 巨噬細胞之生理功能……………………………………………...3
第三節 小神經膠質細胞之生理功能……………………………………...4
第四節 癌症與細胞週期及白血病之介紹………………………………...5
第五節 研究動機與目的…………………………………………………...9
第二章 結果與討論
第一節 化學合成…………………………………………………………...10
壹. 標的化合物的合成概述………………………….. ……………...10
第二節 藥理活性試驗結果……………………………………..………….49
壹. 肥胖細胞脫顆粒反應之抑制活性………………………………..49
貳. 嗜中性白血球脫顆粒反應之抑制活性…………………………..65
參. 嗜中性白血球過氧化物形成之抑制活性………………………..82
肆. 一氧化氮蓄積之抑制活性………………………………………. 99
伍. TNF-α形成之抑制活性…………………………………………116
陸. 抑制癌細胞增生活性試驗………………………………………130
第三章 結論…………………………………………………………………….139
第四章 實驗部份
第一節 試藥及溶媒……………………………………………………….141
第二節 重要儀器………………………………………………………….143
第三節 各化合物之製備………………………………………………….145
第四節 藥理試驗方法…………………………………………………….194
參考文獻………………………….. ………………………………………………200
圖譜………………………………………………………………………………...207
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