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目 錄 誌 謝--------------------------------------------------- Ⅰ縮 寫--------------------------------------------------- Ⅱ 表目錄--------------------------------------------------- Ⅲ 圖目錄--------------------------------------------------- Ⅳ 壹、中文摘要--------------------------------------------- 1 英文摘要-------------------------------------------- 3貳、緒 論 一、導論---------------------------------------------- 5二、合成動機------------------------------------------- 18 參、合成方法、結構鑑定、結果與討論 一、合成方法大綱--------------------------------------- 19 甲、起始原料之合成略圖 乙、3-Alkyl-6-amino-與6-amino-3-aryl-1,2,4-triazolo- [3,4-f][1,2,4]triazin-8(7H)-ones之合成略圖 丙、3-Alkylamino-6-amino-與6-amino-3-arylamino- 1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-ones 之合成略圖 丁、3-Alkylsulfanyl-6-amino-1,2,4-triazolo- [3,4-f][1,2,4]triazin-8(7H)-ones之合成略圖 戊、5-Amino-3-aryl-1,2,4-triazolo- [4,3-d][1,2,4]triazines之合成略圖 二、合成各論 甲、單環雜環1,2,4-triazine環上取代衍生化合物之合成 (一)6-(2-Acylhydrazino)-3-amino-1,2,4-triazin- 5(2H)-ones衍生化合物之合成﹑結構鑑定﹑結果與 討論------------------------------------------- 23 (二)3-Amino-6-(2-substitutedmethylenehydrazino)- 1,2,4-triazin-5(2H)-ones衍生化合物之合成﹑結構 鑑定﹑結果與討論-------------------------------- 30 (三)3-Amino-6-(4-N-substitutedthiosemicarbazido)- 1,2,4-triazin-5(2H)-ones衍生化合物之合成﹑結構 鑑定﹑結果與討論-------------------------------- 37 (四)5-(2-Acylhydrazino)-3-amino-1,2,4-triazines衍生 化合物之合成﹑結構鑑定﹑結果與討論-------------- 43 乙、雙環雜環6-Amino-3-substituted-1,2,4-triazolo- [3,4-f][1,2,4]triazin-8(7H)-ones 衍生化合物之合成 (一)3-Alkyl-6-amino-與6-amino-3-aryl-1,2,4-triazolo- [3,4-f][1,2,4]triazin-8(7H)-ones衍生化合物之合成、 結構鑑定、結果與討論----------------------------- 49 (二)3-Alkylamino-6-amino-與6-amino-3-arylamino-1,2,4- triazolo[3,4-f][1,2,4]triazin-8(7H)-ones衍生化合 物之合成、結構鑑定、結果與討論------------------ 63 (三)3-Alkylsulfanyl-6-amino-與6-amino-3-arylsulfanyl- 1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-ones衍生 化合物之合成、結構鑑定、結果與討論-------------- 66 丙、雙環雜環5-Amino-3-aryl-1,2,4-triazolo- [4,3-d][1,2,4]triazines衍生化合物之合成、結構鑑定、 結果與討論-------------------------------------- 74肆、實驗部分 一、儀器及試藥部分-------------------------------------- 82 二、合成部分-------------------------------------------- 86 甲、單環雜環1,2,4-triazine及其環上取代衍生化合物之製備 (一)起始原料之製備---------------------------------- 86 (二)6-(2-Acylhydrazino)-3-amino-1,2,4-triazin- 5(2H)-ones衍生化合物之製備---------------------- 88 (三)3-Amino-6-(2-substitutedmethylenehydrazino)- 1,2,4-triazin-5(2H)-ones衍生化合物之製備-------- 91 (四)3-Amino-6-(4-N-substitutedthiosemicarbazido)- 1,2,4-triazin-5(2H)-ones衍生化合物之製備-------- 98 (五)5-(2-Acylhydrozino)-3-amino-1,2,4-triazines 衍生化合物之製備------------------------------- 100 乙、雙環雜環6-Amino-3-substituted-1,2,4-triazolo- [3,4-f][1,2,4]triazin-8(7H)-ones衍生化合物之製備 (六)3-Alkyl-6-amino-1,2,4-triazolo- [3,4-f][1,2,4]triazin-8(7H)-ones衍生化合物 之製備------------------------------------------ 103 (七)6-Amino-3-aryl-1,2,4-triazolo- [3,4-f][1,2,4]triazin-8(7H)-ones衍生化合物 之製備----------------------------------------- 105 (八)3-Alkylamino-6-amino-1,2,4-triazolo- [3,4-f][1,2,4]triazin-8(7H)-ones衍生化合物 之製備----------------------------------------- 106 (九)6-Amino-3-arylamino-1,2,4-triazolo- [3,4-f][1,2,4]triazin-8(7H)-ones衍生化合物 之製備----------------------------------------- 107 (十)3-Alkylsulfanyl-6-amino-1,2,4-triazolo- [3,4-f][1,2,4]triazin-8(7H)-ones 衍生化合物 之製備----------------------------------------- 107 丙、雙環雜環5-Amino-3-aryl-1,2,4-triazolo- [4,3-d][1,2,4]triazines衍生化合物之製備-------- 109 伍、生物活性測試----------------------------------------- 113 陸、參考文獻--------------------------------------------- 121柒、附錄------------------------------------------------- 124
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陸、參 考 文 獻 1. 行政院衛生署衛生統計資訊網 http://www.doh.gov.tw/newdoh/90-org/org-10/org-10-2.htm 2. C. Huggins and C. V. Hodges, Cancer Res., 1941, 1, 293. 3. A. Gilman and F. S. Philips, Science, 1946, 103, 409. 4. O.H. Pearson, Cancer, 1949, 2, 943. 5. D. D. Woods, Br J. Exp. Pathol., 1940, 21, 74. 6. P. Fildes, Lancet, 1940, 955. 7. J. A. Montgomery et al., Medicinal Chemistry, 3rd ed., 1970, 680. 8. A. R. P. Patterson, D. M. Tidd, Handbook of Experimental Pharmacology, 1975, 38(Ⅱ), 384. 9. R. O. Roblin et al., J. Am. Chem. Soc., 1945, 67, 290. 10. G. H. Hitchings and G. B. Elion, Accounts Chem. Res., 1969, 2, 202. 11. G. B. Elion, Fed. Proc., 1967, 26, 898. 12. W. W. Lee et al., J. Am. Chem. Soc., 1960, 82, 2648. 13. Davis Parke, Belg. Co., Patent, 1967, 671, 557. 14. J. J. Furth and S. S. Cohen, Cancer Res., 1967, 27, 1528. 15. N. R. Lomax and V. L. Narayanan, Chemical Structures of Interest to the Division of Cancer Treatment, NCI, 1979 Jan.. 16. C. Heidelberger: Flourinated Pyrimidines and Their Nucleosides, In A. C. Sartorelli and D. J. Johns(eds.): Handbook of Experimental Pharmacology, 1975, 38(Ⅱ), 193. 17. S. R. Williams, J. M. Goddard and D. W. Martin, Nucleic Acids Res., 1984, 12, 5779. 18. R. E. Parks, Jr., R. P. In. Agarwal, The Enzymes, 3rd ed., P. D. Boyer, Ed., Academic Press: New York, 1972, 7, 483. 19. J. A. Montgomery, Exp. Opin. Invest. Drugs, 1994, 3, 1303. 20. M. Weibel, J. Balzarini, A. Bernhardt and P. Mamont, Biochem. Pharmacol., 1994, 48, 245. 21. C. E. Bugg, W. M. Carson and J. A. Montgomery, Drugs by design. Sci. Am., 1993, 269, 60. 22. S. E. Ealick, Y. S. Babu, C. E. Bugg, M. D. Erion, W. C. Guida, J. A. Montgomery and J. A. Secrist, Proc. Nati. Acad Sci., USA 88, 1991, 11540. 23. J. A. Montgomery, S. Niwas, J. D. Rose, J. A. Secrist, Y. S. Babu, C. E. Bugg, M.D. Erion, W. C. Guida and S. E. Ealick, J. Med. Chem., 1993, 36, 55. 24. J. A. Secrist, S. Niwas, J. D. Rose, Y. S. Babu, C. E. Bugg, M. D. Erion, W. C. Guida, S. E. Ealick and J. A. Montgomery, J. Med. Chem., 1993, 36, 1847. 25. M. D. Erion, S. Niwas, J. D. Rose et al., J. Med. Chem., 1993, 36, 3771. 26. W. C. Guida, R. D. Elliott, H. J. Thomas and J. A. Secrist, Y. S. Babu, C. E. Bugg, M. D. Erion, S. E. Ealick, J. A. Montgomery, J. Med. Chem., 1994, 37, 1109. 27. S. E. Ealick, S. A. Rule and D. C. Carter et al., J. Biol. Chem., 1990, 265, 1812. 28. S. K. Burley and C. A. Petsko, Science , 1985, 229, 23. 29. T. Yokomatsu, Y. Hayakawa, T. Kihara, S. Koyanagi et al., Bioorganic & Medicinal Chemistry, 2000, 8, 2571. 30. M. D. Erion, S. Niwas, J. D. Rose et al., J. Med. Chem., 1993, 36, 3771. 31. V. Farutin, L. Masterson, A. D. Andricopulo, J. Cheng et al., J. Med. Chem., 1999, 42, 2422. 32. H. Neunhoeffer and P. F. Wiley, Chemistry of 1,2,3-Triazines and 1,2,4-Triazines, Tetrazines and Pentazines, ed. A. Weissberger and E. C. Taylor, 1978, J. Wiley and Sons, New York, Chichester, Brisbane, Toronto, 1001-1004. 33. E. S. H. EL Ashry, N. Rashed, M. Taha, and E. Ramadan, Condensed 1,2,4-Triazines:Ⅰ. Fused to Heterocycles with Three-, Four-, and Five- Membered Rings, Advances in Heterocyclic Chemistry, 1994, 59, 41. 34. E. S. H. EL Ashry, N. Rashed, A. Mousaad, and E. Ramadan, Condensed 1,2,4-Triazines: Ⅱ. Fused to Heterocycles with Six-, Seven-Membered Rings and Fused to Two Heterocyclic Rings, Advances in Heterocyclic Chemistry, 1994, 61, 209. 35. C. A. Lovelette, J. Heterocyclic chem., 1979, 16, 555. 36. S. Scheibye, J. Kristensen and S. O. Lawesson, Tetrahedron, 1979, 35, 1339. 37. B. S. Pedersen and S. O. Lawesson, Tetrahedron, 1979, 35, 2433. 38. K. Kaneko, H. Katayama, T. Wakabayashi et al., Communications, 1988, 152. 39. P. C. Michael and I. L. Matthew, Tetrahedron, 1985, 41, 5061.
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