臺灣博碩士論文加值系統

Thalidomide為glutamic acid的合成衍生物，目前已被研究出具有多種藥理機轉，像是抗發炎、抗血管增生以及免疫調節的作用，現今多用於治療多種癌症及免疫性疾病，但臨床上仍然有許多副作用需改善。本研究的目的為設計、合成出新一代thalidomide的衍生物，針對glutarimide ring上作修飾，在氮原子上藉由一段spacer連接疏水性基團，並探討其抗發炎活性。其中，我們發現化合物38針對IL-6以及TNF-兼具有高度的抑制效果。未來我們將繼續針對化合物38研究出更詳細的藥理機轉，或將其衍生，希望能開發出具有低副作用、高度抗發炎活性潛力之藥物。

Thalidomide, a synthetic glutamic acid derivative, have been demonstrated to possess various pharmacological effects such as anti-inflammatory, anti-angiogenetic, and immunomodulatory activities. It is widely used nowadays in clinical to treat cancers and immunology diseases. There are, however, still a lot of side effects exhibited by the treatment of thalidomide, including severe teratogenicity which needed to be improved. In this study, we have designed and synthesized novel thalidomide derivatives, which added different substituted aryl groups to glutarimide ring on the thalidomide through different type of spacers. Among them, compound 38 demonstrated an excellent inhibition in both IL-6 and TNF-. We believe that compound 38 can serve as an excellent lead for further development of potential drug candidates.

表目錄 III
圖目錄 IV
中文摘要 1
英文摘要 2
壹、 緒論 3
貳、 研究動機 9
參、 合成方法、結果與討論 15
一、 Thalidomide衍生物的逆合成分析 15
二、 Thalidomide衍生物之合成實驗結果與討論 18
肆、 體外抗發炎活性結果與討論 25
一、 體外抗發炎活性結果 25
二、 結構活性關係討論 33
伍、 結論 35
陸、 實驗部分 36
一、 溶劑及處理過程 36
二、 儀器 37
三、 試藥 38
四、 各化合物之製備 41
柒、 參考文獻 89

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