1(或2)-(取代芐基)-3-(4-甲基苯基)-1(或2)氫-吲唑類化合物之合成及其抗血小板、抗血管增生與細胞致毒活性; Synthesis, Antiplatelet, Antiangiogenesis and Cytotoxicity Activity of 1(or 2)-(Substituted benzyl)-3-(4-methylphenyl)-1(or 2)H-indazoles

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題名:	1(或2)-(取代芐基)-3-(4-甲基苯基)-1(或2)氫-吲唑類化合物之合成及其抗血小板、抗血管增生與細胞致毒活性;Synthesis, Antiplatelet, Antiangiogenesis and Cytotoxicity Activity of 1(or 2)-(Substituted benzyl)-3-(4-methylphenyl)-1(or 2)H-indazoles
作者:	石美玲;Shih Mei-Ling
貢獻者:	中國醫藥學院藥物化學研究所
關鍵詞:	抗血小板凝集;抗血管增生;細胞致毒;YD-3 衍生物;唑類衍生物;antiplatelet;antiangiogenesis;cytotoxicity;YD-3 derivatives;indazole derivatives
日期:	1991
上傳時間:	2009-12-03 10:03:33 (UTC+8)
摘要:	為了得到強力的抗血小板與抗血管增生之化合物，所以著者以3-(4-methylphenyl)-1H-indazole (6)為key intermediate，從事其衍生物的合成。利用1-N-嗎福啉基環己烯與4-甲基苯甲醯氯在三乙基胺的存在下反應，接著以鹽酸水溶液水解即可得2-oxocyclohexyl 4- methylphenyl ketone (4)。將化合物4與聯胺進行反應，可以得到3-(4-methylphenyl)-4,5,6,7-tetrahydro-1H-indazole (5)。繼而以Pd/C之催化脫氫反應將化合物5氧化成3-(4-methylphenyl)-1H-indazole (6)。最後將化合物6與各種取代的芐基氯進行benzylation 後，形成兩類主要的衍生物；1-(substituted benzyl)-3-(4-methylphenyl)-1H-indazole (7、9、11、13、15、16、18)與2-(substituted benzyl)-3-(4-methylphenyl)-2H-indazole (8、10、12、14、17、19 - 21)。將化合物6及其相關化合物進行生物活性之評估。結果發現大部份N2取代性衍生物(8、10、12、14、17、19 - 21)比N1取代性衍生物(9、11、13、15、16)具有較顯著的抗血小板活性。而在N2取代性衍生物中，2-(4-chlorobenzyl)-3-(4-methylphenyl)-2H-indazole (8), 2-(4-methylbenzyl)-3-(4-methylphenyl)-2H-indazole (14) 以及 2-(4-methoxybenzyl)-3-(4-methylphenyl)-2H-indazole (19)具有顯著的抗血管增生活性，值得進一步探討。; In order to search novel compounds with potent antiplatelet and antiangiogenesis activities, 3-(4-methylphenyl)-1H-indazole (6) was used as the key intermediate and its derivatives were synthesized. In the presence of triethylamine, 1-(N-morpholino)cyclohexene was reacted with 4-methylbenzoyl chloride. Followed by hydrolysis using dil. hydrochloric acid, 2-oxocyclohexyl 4-methylphenyl ketone (4) was obtained. 3-(4-Methylphenyl)-4,5,6,7-tetrahydro-1H-indazole (5) was gained after reaction of compound 4 and hydrazine. The product, 3-(4-methyl phenyl)-1H-indazole (6), was obtained after compound 5 was oxygenated by catalytic dehydrogenation on Pd/C. Finally, benzylation of compound 6 with various substituted benzyl chloride produced the derivatives, 1-(substituted benzyl)-3-(4-methylphenyl)-1H-indazoles (7、9、11、13、15、16、18) and 2-(substituted benzyl)-3-(4-methyl phenyl)-2H-indazoles (8、10、12、14、17、19 - 21). Compound 6 and its related compounds were evaluated for their biological activities. Most of N2-substituted derivatives (8、10、12、14、17、19、20、21) showed more prominent antiplatelet activity than N1-substituted derivatives (9、11、13、15、16). Among these N2-substituted derivatives, 2-(4-chlorobenzyl)-3-(4-methylphenyl)-2H-indazole (8), 2-(4-methylbenzyl)-3-(4-methylphenyl)-2H-indazole (14) and 2-(4-methoxybenzyl)-3-(4-methylphenyl)-2H-indazole (19) showed significant antiangiogenesis and worthy for further investigation.
顯示於類別:	[藥物化學研究所] 博碩士論文

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