臺灣博碩士論文加值系統

1-苄基-3-(5-羥甲基-2-呋喃基)吲唑(YC-1)被認為是具有潛力的抗癌藥，為了進一步探討YC-1類緣化合物的結構與活性關係，此研究著者合成一系列selenolo[3,2-c]pyrazoles的標的化合物。
以醯氯化合物5-6與2-呋喃甲酯進行醯化反應，可獲得關鍵中間體7-8，再將7-8與苯肼或有取代的苯肼反應，產生E及Z型腙類異構物混合物，再以四醋酸鉛及三氟化硼混合物進行環化反應，即可獲得化合物27-35，接著將化合物27-35以氫硼化鈣進行還原反應，即可得醇類化合物36-40，或進行水解反應產生酸類化合物41-42。
將所合成的化合物27-35、36-40、41-42進行對人類腎癌A-489及非小細胞肺癌NCIH-226細胞株之致毒活性試驗，其結果顯示，醇類化合物3-(5-hydroxymethyl-2-furyl)-1-phenyl-5-methylselenolo-
[3,2-c]pyrazole (36)與3-(5-hydroxymethyl-2-furyl)-1-phenylselenolo[3,2-c]pyrazole (37)對人類腎癌細胞株A-489有明顯的細胞致毒活性。

1-Benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) was has been identified as a potential antitumor agent. In order to extend the structure-activity relationships of YC-1 analogs, in this study a series of selenolo[3,2-c]pyrazoles were synthesized as target compounds.
The key intermediates 7-8 were synthesized by reacting acyl chlorides 5-6 with methyl furan-2-carboxylate. The reacted intermediates 7-8 were then treated with phenylhydrazine or substituted phenylhydrazine to give the corresponding hydrazones 9-17. The above hydrazones were then treated with mixed reagents of lead tetraacetate and boron trifluoride etherate cyclization to yield the designed compounds 27-35. These selenolo[3,2-c]pyrazoles 27-35 were reduced with calcium borohydride to afford their corresponding carbinol derivatives 36-40 and hydrolyzed to give their corresponding carboxylic acids 41-42.The newly synthesized compounds 27-42 were evaluated for their cytotoxicity against human renal A-498 and non-small cell lung cancer NCI-H226 cell lines. The results demonstrate that the carbinol derivatives 3-(5-hydroxymethyl-2-furyl)-1-phenyl-5-methylselenolo[3,2-c]pyrazole- (36) and 3-(5-hydroxymethyl-2-furyl)-1-phenylselenolo[3,2-c]pyrazole-
(37) show significant cytotoxity against human renal cancer cell line A498.

圖 目 錄…………………………………………………………….III
圖譜目錄……………………………………………………………......IV
表 目 錄……………………………………………………….......…V
化 合 物 代 號 與 結 構 對 照 表………………………………..XI
中文摘要…………………………………………………..………….XIV
英文摘要………………………………………………….………..….XV
第一章 緒論…………………………….………………………………1
第一節YC-1之研究概況……………………………………………..1
I. cGMP 依存性的藥理作用..................................…………….2
II. 優越抗癌活性.............................…....………………………...3
第二節 硒吩( Selenophene)及硒(Selenium)之結構及物理性質........7
I. Selenophene與Benzene的鍵長與鍵角……………..………..7
II. Selenophene及Benzene的物理性質…………....………...…..8
III. Selenophene及Benzene的芳香性質………….....….....…….9
IV. 硒(Selenium) 介紹………………………………..……...…10
第二章 研究動機與目的...…………………………………..….....12
第三章 結果與討論.……………………………..……………….14
第一節 化學合成……………………………………………………14
第二節 生物活性試驗結果結果……………...…………………….20
第四章 結論……………………………………………………………22
第五章 實驗部分………………………………………………………24
第一節 試藥與溶媒…………………………………………………24
第二節 重要儀器與實驗材料………………………………………27
第三節 化合物製備…………………………………………………30
I. 3-(5-Substituted-2-furyl)-1-phenyl-5-methylselenolo[3,2-c]-
pyrazole之合成...………………....…….....…................……..30
II. 3-(5-Substituted-2-furyl)-1-phenylselenolo[3,2-c]pyrazole之
合成...……………....…………..........................……...............42
III. 3-(5-Substituted-2-furyl)-1-(substituted-phenyl)selenolo-
[3,2-c]pyrazole之合成...….................................................….52
第四節 藥理試驗方法……………………………………………..72
參考文獻………………………………………………………………..73
圖譜資料………………………………………………………………..77

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