3-(5-羥甲基-2-呋喃基)-1-苯基-硒吩[3,2-c]吡唑
類緣化合物之合成與抗癌活性; Synthesis and anticancer activity of 3-(5-hydroxymethyl-2-furyl)-1-phenyl-selenolo[3,2-c]pyrazole analogs

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Title:	3-(5-羥甲基-2-呋喃基)-1-苯基-硒吩[3,2-c]吡唑類緣化合物之合成與抗癌活性;Synthesis and anticancer activity of 3-(5-hydroxymethyl-2-furyl)-1-phenyl-selenolo[3,2-c]pyrazole analogs
Authors:	方美琪;Mei-Chi Fang
Contributors:	中國醫藥大學：藥物化學研究所碩士班
Keywords:	硒;selenophene
Date:	2008-07-17
Issue Date:	2009-08-13 09:37:30 (UTC+8)
Abstract:	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.
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