臺灣博碩士論文加值系統

在先前的研究，我們發現苯類化合物於體外測試有顯著的黃嘌呤氧化抑制活性．2-amino-4H-1,3-benzothiazin-4-one (BJ-6) (IC50 = 5.54μM，Ki = 5.12μM) 以及 4-oxo-4H-1,3-benzothiazinone-2-guanidine (TDW-1) (IC50 = 5.60μM，Ki = 19.47μM)是這一類的代表。
於本研究，我們製備一些與苯類的結構有所關聯之化合物，包括類、苯類，和三環的苯類化合物，為了研究其對該酵素的抑制活性，然而，只有tetrazolo [5, 1-b] [1, 3] benzothiazin-9-one (BJ-4)，於200μM濃度時有38.1％的抑制活性，其他則沒有活性。
另外，我們以Blois氏方法對自由基清除活性進行測試，發現2-hydrazino-4H-1, 3-benzothiazin-4-one (BJ-3) (IC50=23.29 ±0.02 μM), 4-hydrazino-2H-1, 3-benzothiazin-2-thione (BJ-5) (IC50=19.60 ±0.02 μM)和4-hydrazino-2H-1, 3-benzothiazin-2-one (BJ-702) (IC50=23.14 ±0.01 μM)與α-tocopherol (IC50=24.69 ±0.01 μM)比較，其對DPPH自由基清除具有相當好的活性。

In a previous study, we found that benzothiazinone compounds displayed a significant inhibition on xanthine oxidase in in vitro test. 2-Amino-4H-1,3-benzothiazin-4-one (BJ-6) (IC50 = 5.54μM, Ki = 5.12μM) and 4-oxo-4H-1,3-benzothiazinone-2-guanidine (TDW-1) (IC50 = 5.60μM, Ki = 19.47μM) are the representatives of this class.
In this study, we prepared several thiazinone analogues, benzothiazinone analogues, and tricyclic benzothiazinones that are structurally related to the benzothiazinone in order to search for the pharmacophore for enzyme inhibition. However, we found that only tetrazolo [5, 1-b] [1, 3] benzothiazin-9-one (BJ-4) is the compound showed 38.1% xanthine oxidase inhibition at 200μM level, others were apparently inactive.
In addition, we also clarified the free radical scavenging activity of these compounds by virtue of Blois method, we found 2-hydrazino-4H-1, 3-benzothiazin-4-one (BJ-3) (IC50 = 23.29 ± 0.02 μM), 4-hydrazino-2H-1, 3-benzothiazin-2-thione (BJ-5) (IC50 = 19.60 ± 0.02 μM) and 4-hydrazino-2H-1, 3-benzothiazin-2-one (BJ-702) (IC50 = 23.14 ± 0.01 μM) showed DPPH free radical scavenging activity comparable to that of α-tocopherol (IC50 = 24.69 ± 0.01 μM).

目錄
附圖目錄
附表目錄
縮寫表
中文摘要
英文摘要
壹、 緒論
一、 研究背景
(一) 黃嘌呤氧化的介紹
(三) 臨床上使用黃嘌呤氧化抑制劑情形
(四) 自由基與疾病關係
(五) Benzothiazinones之研究歷史
二、 研究目的
貳、 材料與方法
一、 材料與儀器
(一) 實驗儀器
(二) 試藥及試劑
二、 合成反應綱要
三、 實驗方法
(一) 化學合成部份
A. 雙環1, 3-Benzothiazinones
2-Mercapto-4H-1,3-benzothizin-4-one (BJ-1)之製備
2-Methylthio-4H-1, 3-benzothiazin-4-one (BJ-2)之製備
2-Hydrazino-4H-1, 3-benzothiazin-4-one (BJ-3)之製備-
4-Hydrazino-2H-1, 3-benzothiazin-2-thione (BJ-5) 之製備
2-Amino- 1, 3-benzothiazine-4-one( BJ-6 )之製備
1, 3-Benzothiazine-2, 4-dione (BJ-7)之製備
2-<2-Amino-oxathiolane-2-yl-mercapto>-benzoic acid (BJ-201)之製備
4-Hydrazino-2H-1, 3-benzothiazin-2-one (BJ-702)之製備
B. 單環之Thiazinones
2-Amino-5, 6-dihydro-1, 3-thiazine-4-one (Thia-1)之製備
2-Amino-4-oxo-4H-1, 3-thiazine-6-carboxylic acid methyl ester (Non-1)之製備
C. 參環Benzothiazinones
1, 2, 4-Triazolo [3, 4-b] 1, 3-benzothiazin-5-one (BJ-15)之製備-
1, 2, 4-Triazolo [5, 1-b] 1, 3-benzothiazin-9-one (BJ-16)之製備
Tetrazolo [5, 1-b] [1, 3] benzothiazin-9-one (BJ-4)之製備
(二) 黃嘌呤氧化活性抑制測試部份
A 實驗材料
B 方法
(三) 自由基消除活性測試部份
A 實驗材料
B 方法
參、 結果
(一) 化學合成部份
(二) 黃嘌呤氧化活性抑制測試部份
(三) 自由基消除活性測試部份
肆、 討論
(一) 化學合成部份
(二) 黃嘌呤氧化活性抑制測試部份-
(三) 自由基消除活性測試部份
伍、 總結
陸、 附圖部份
柒、 參考文獻

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