臺灣博碩士論文加值系統

鉀離子通道打開劑，例如cromakalim，是一種有效的平滑肌舒張劑，並且顯示具有治療不同的心臟血管及肺支氣管疾病的潛力，特別是應用在氣喘、高血壓、大小便失禁等。自從1986年cromakalim被發現是一有效的降血壓藥物後，許多以的benzopyran為主的類似物被熱門的研究著，我們研究鉀離子之血管舒張劑課題時，我們認為將benzopyran（苯并哌喃）修改成naphthopyran（萘并哌喃），兩者的芳香環上電子之分佈相似，因而可以預期會得到類似的藥理活性，因此我們合成了一系列４取代萘并哌喃衍生物24-27及33-35和39-41這些化合物以老鼠胸腔動脈血管做舒張活性測試，發現25a活性較好，其EC50為0.22μM。

Potassium channel openers, such as cromakalim, are potent smooth muscle relaxants which have been shown to have potential therapeutic application in a variety of cardiovascular and bronchopulmonary diseases, particularly in asthma, hypertension, and urinary incotinence. Cromakalim, the first benzopyran type potassium channel opener, was found as a potent antihypertensive agent in 1986. After that there have been numerous reports on modification of substituents at different positions of benzopyran ring, but few reports on modification of the benzopyran nucleus itself. In the course of our studies on new hypotensive potassium channel openers, we considered replacing the benzopyran ring with naphthopyran ring and this change would not affect the electronic nature of the aromatic ring. Therefore, a new series of 4-substituted naphthopyrans (24-27, 33-35, 39-41) have been prepared and their vasorelaxant activities have been evaluated. Among them, 25a showed more potent vasorelaxant activity (EC50= 0.22 μM) on isolated rat thoracic aorta precontracted with phenylephrine.

目 錄
頁數
流程圖目錄-------------------------------------------------i
圖表目錄---------------------------------------------------ii
摘要-------------------------------------------------------iii
英文摘要---------------------------------------------------iv
壹、緒論
1-1研究背景------------------------------------------------01
1-2 研究動機 ----------------------------------------------02-03
1-3 研究目的 ----------------------------------------------06
貳、 儀器與材料
2-1 儀器 --------------------------------------------------07
2-2 材料 --------------------------------------------------08-10
參、 研究方法
3-1 合成方法 SchemeⅠ---------------------------------------------------11-12
3-2 合成方法SchemeⅡ---------------------------------------------------11
3-3 合成方法SchemeⅢ---------------------------------------------------12
3-4 活性測定 -----------------------------------------13
肆、 實驗部分
4-1 合成部分 -----------------------------------------18-37
4-2 活性測定方法 -------------------------------------37-38
伍、 結果討論
5-1 合成探討 -----------------------------------------39
5-2 結構判定 -----------------------------------------42
5-3 活性探討 -----------------------------------------43-44
陸、 參考文獻 ---------------------------------------------47-49
流程圖目錄
1、 SchemeI------------------------------------------------14
2、 SchemeⅡ-----------------------------------------------15
3、 SchemeⅢ-----------------------------------------------16
4、 SchemeⅣ--------------------------=------------------- 40
5、 SchemeⅤ---------------------------------------------- 41
6、 SchemeⅥ---------------------------------------------- 45
圖 表 目 錄
1、 ChartⅠ------------------------------------------------04
2、 ChartⅡ------------------------------------------------05
3、 Table 1------------------------------------------------43
4、 Table 2------------------------------------------------45
5、 Table 3------------------------------------------------46
6、 Fig 1 : 24b 1H-----------------------------------------50
7、 Fig 2 : 24b 13C----------------------------------------51
8、 Fig 3 : 28 1H------------------------------------------52
9、 Fig 4 : 28 13C-----------------------------------------53
10、 Fig 5 : 39 1H-----------------------------------------54
11、 Fig 6 : 39 13C ---------------------------------------55
12、 Fig 7 : 39 COSY --------------------------------------56
13、 Fig 8 : 39 HMQC---------------------------------------57
14、 Fig 9 : 39 HMBC---------------------------------------58
15、 Fig 10 : 41 1H----------------------------------------59
16、 Fig 11 : 41 13C---------------------------------------60
17、 Fig 12 : 34 LC/MS-------------------------------------61
18、 Fig 13 : 35 LC/MS ------------------------------------62
19、 Fig 14 : 40 LC/MS ------------------------------------63
20、 Fig 15 : 41 LC/MS ------------------------------------64

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