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研究生:李俊誼
研究生(外文):Lee Chun-Yi
論文名稱:4,5-二苯基1,2,3-三氮唑的合成與抗癌活性研究
論文名稱(外文):Synthesis and cytotoxic activities of 4,5-diaryl 1,2,3-triazoles
指導教授:黎世源黎世源引用關係董明兆董明兆引用關係
指導教授(外文):Li, S.-Y.Don, Ming-Jaw
口試委員:沈建昌郭文貴
學位類別:碩士
校院名稱:中國文化大學
系所名稱:應用化學研究所
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:中文
論文頁數:160
中文關鍵詞:抗癌活性研究三氮唑的合成
外文關鍵詞:triazolescytotoxic activities
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Combretastatins是從南非一種柳樹(Combretum caffrum)的樹皮中分離出來屬於stilbene類的天然物,其中 combretastatin A-4 (CA-4)為combretastatin系列化合物中抑制微管蛋白聚合的活性表現最好,不僅能夠有效的抑制癌細胞增生,同時也能破壞腫瘤內的血管,造成腫瘤細胞死亡。
先前的研究顯示combretastatin化合物的順式構型對表現很強的抗癌活性是重要的,但此類化合物會在儲存時異構化變成反式構型,而反式構型的combretastatin化合物會使抑制癌細胞增生與抑制微管蛋白聚合的活性降低許多。
為了研發新抗癌藥物,本研究設計以1,2,3-triazole五元環來替代CA-4的結構的碳碳雙鍵,使結構中兩個苯環保持順式構型,合成一系列4,5-diaryl-1,2,3-triazoles化合物,同時進行人類癌細胞的細胞毒殺活性,癌細胞包括人類子宮上皮癌細胞、人類肝臟癌細胞及人類卵巢癌細胞,這些合成的化合物中,以化合物10的細胞毒殺活性最強,其IC50值為1.49 – 1.85 nM。

Combretastatins, naturally occurring stilbenes, were isolated from Combretum caffrum (African Bush Willow). Among them, combretastatin A-4 (CA-4) strongly inhibited the polymerization of tubulin by binding to the colchicine site and showed most potent cytotoxicity against a variety of human cancer cell lines including multiple drug resistant cancer cell lines. CA-4 also showed strong anti-vascular activity.
In the previously comparative studies of the combretastatins it appears that the cis orientation of the two aromatic rings plays an important key role of cytotoxicity. However, during storage and administration cis-combretastatin analogues tend to isomerize to trans-form. The trans-form of these compounds shows a dramatic decrease in the inhibitory effects on cancer cell growth and tublin polymerization.
In order to develop new anticancer drugs, triazole ring was utilized to replace the cis double bond in CA-4. A series of 4,5-diaryl-1,2,3-triazoles were prepared and their cytotoxic activity were also evaluated against human cancer cell lines including human cervical epitheloid carcinoma (HeLa), human hepatocellular carcinoma (HepG2), and human ovarian adenocarcinoma (OVCAR-3). Among the synthesized compounds, compound 10 was the most potent compound in this series with an IC50 value 1.49 – 1.85 nM.

目 錄
中文摘要 ----------------------------------------------------------------------- I
英文摘要 ----------------------------------------------------------------------- II
目錄 ----------------------------------------------------------------------------- III
圖表目錄 ----------------------------------------------------------------------- IV
壹、緒論 ----------------------------------------------------------------------- 1
貳、實驗儀器與藥品--------------------------------------------------------- 7
參、研究方法------------------------------------------------------------------ 11
肆、實驗步驟 ----------------------------------------------------------------- 17
伍、結果與討論 -------------------------------------------------------------- 48
陸、參考文獻 ----------------------------------------------------------------- 58
柒、圖表附錄 ----------------------------------------------------------------- 63




圖 表 目 錄
Fig. 1. Vinorelbine與taxol的結構 ------------------------------------- 2
Fig. 2. Colchicine、CA-4與CA-4P的結構 ------------------------- 3
Fig. 3. 細胞週期示意圖---------------------------------------------------- 3
Fig. 4. 以環狀結構固定cis結構的CA-4的類似物------------------ 5
Fig. 5. 化合物4,5-diarylisoxazole ---------------------------------------- 6
Fig. 6. 化合物4,5-diaryl-1,2,3-triazoles --------------------------------- 6
Fig. 7. 含萘環之化合物結構----------------------------------------------- 6
Fig. 8. 化合物9、10、21、22、23、24與25結構------------------ 56
Fig. 9. 化合物9、10、21與27之結構--------------------------------- 57
Fig. 10. 化合物21與CA-4之結構--------------------------------------- 57
Fig. 11. 化合物5-(2,2-dibromovinyl)-1,2,3-trimethoxybenzene (1)的1H-NMR圖譜--------------------------------------------------- 63
Fig. 12. 化合物5-(2,2-dibromovinyl)-1,2,3-trimethoxybenzene (1)的13C-NMR圖譜--------------------------------------------------- 64
Fig. 13. 化合物3,4,5-trimethoxyphenylacetylene (2)的1H-NMR
圖譜------------------------------------------------------------------ 65
Fig. 14. 化合物3,4,5-trimethoxyphenylacetylene (2)的13C-NMR
圖譜------------------------------------------------------------------- 66
Fig. 15. 化合物4-iodo-2-nitroanisole (3)的1H-NMR圖譜-------- 67
Fig. 16. 化合物4-iodo-2-nitroanisole (3)的 13C-NMR圖譜--------- 68
Fig. 17. 化合物benzyl azide (4)的1H-NMR圖譜-------------------- 69
Fig. 18. 化合物benzyl azide (4)的13C-NMR圖譜------------------ 70
Fig. 19. 化合物1,2,3-trimethoxy-5-((4-methoxyphenyl)ethynyl)benzene (5)的1H-NMR圖譜----------------------------------------------- 71
Fig. 20. 化合物1,2,3-trimethoxy-5-((4-methoxyphenyl)ethynyl)benzene (5)的13C-NMR圖譜---------------------------------------------- 72
Fig. 21. 化合物1,2,3-trimethoxy-5-((4-methoxy-3-nitrophenyl)-
ethynyl)benzene (6)的1H-NMR圖譜------------------------ 73
Fig. 22. 化合物1,2,3-trimethoxy-5-((4-methoxy-3-nitrophenyl)-
ethynyl)benzene (6)的13C-NMR圖譜 --------------------- 74
Fig. 23. 化合物1-benzyl-5-(4-methoxyphenyl)-4-(3,4,5-trimethoxy-
phenyl)-1H-1,2,3-triazole (7a)的1H-NMR圖譜------------- 75
Fig. 24. 化合物1-benzyl-5-(4-methoxyphenyl)-4-(3,4,5–trimethoxy-
phenyl)-1H-1,2,3-triazole (7a)的13C-NMR圖譜-------------- 76
Fig. 25. 化合物1-benzyl-4-(4-methoxyphenyl)-5-(3,4,5-trimethoxy-
phenyl)-1H-1,2,3-triazole (7b)的1H-NMR圖譜 ------------- 77
Fig. 26. 化合物1-benzyl-4-(4-methoxyphenyl)-5-(3,4,5-trimethoxy-
phenyl)-1H-1,2,3-triazole (7b)的13C-NMR圖譜------------- 78
Fig. 27. 化合物5-(4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-
1H-1,2,3-triazole (9)的1H-NMR圖譜 ---------------------- 79
Fig. 28. 化合物5-(4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-
1H-1,2,3-triazole (9)的13C-NMR圖譜 --------------------- 80
Fig. 29. 化合物5-(4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-
1H-1,2,3-triazole (9)的COSY圖譜----------------------------- 81
Fig. 30. 化合物5-(4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-
1H-1,2,3-triazole (9)的HMBC圖譜--------------------------- 82
Fig. 31. 化合物5-(4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-
1H-1,2,3-triazole (9)的HMQC圖譜---------------------------- 83
Fig. 32. 化合物5-(4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-
1H-1,2,3-triazole (9)的EI-MS圖譜----------------------------- 84
Fig. 33. 化合物5-(4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-
1H-1,2,3-triazole (9)的FTIR圖譜------------------------------ 85
Fig. 34. 化合物1-benzyl-5-(4-methoxy-3-nitrophenyl)-4-(3,4,5-tri-
methoxyphenyl)-1H-1,2,3-triazole (8a)的1H-NMR圖譜---- 86
Fig. 35. 化合物1-benzyl-5-(4-methoxy-3-nitrophenyl)-4-(3,4,5-tri-
methoxyphenyl)-1H-1,2,3-triazole (8a)的13C-NMR圖譜---- 87
Fig. 36. 化合物1-benzyl-4-(4-methoxy-3-nitrophenyl)-5-(3,4,5-tri-
methoxyphenyl)-1H-1,2,3-triazole(8b)的1H-NMR圖譜---- 88
Fig. 37. 化合物1-benzyl-4-(4-methoxy-3-nitrophenyl)-5-(3,4,5-tri-
methoxyphenyl)-1H-1,2,3-triazole (8b)的13C-NMR圖譜---- 89
Fig. 38. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)aniline (10)的1H-NMR圖譜 ------------------- 90
Fig. 39. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)aniline (10)的13C-NMR圖譜 ------------------ 91
Fig. 40. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)aniline (10)的COSY圖譜------------------------- 92
Fig. 41. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)aniline (10)的HMBC圖譜------------------------ 93
Fig. 42. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)aniline (10)的HMQC圖譜------------------------ 94
Fig. 43. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)aniline (10)的EI-MS圖譜-------------------------- 95
Fig. 44. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)aniline (10)的FTIR圖譜---------------------------- 96
Fig. 45. 化合物5-bromo-2-hydroxybenzoic acid (11)的1H-NMR圖譜 ----------------------------------------------------------------------- 97
Fig. 46. 化合物5-bromo-2-hydroxybenzoic acid (11)的13C-NMR圖譜 ------------------------------------------------------------------- 98
Fig. 47. 化合物methyl 5-bromo-2-methoxybenzoate (12)的1H-NMR圖譜 -------------------------------------------------------------------- 99
Fig. 48. 化合物methyl 5-bromo-2-methoxybenzoate (12)的13C-NMR圖譜 ------------------------------------------------------------------- 100
Fig. 49. 化合物5-bromo-2-methoxyphenol (13)的1H-NMR圖譜---- 101
Fig. 50. 化合物5-bromo-2-methoxyphenol (13)的13C-NMR圖譜--- 102
Fig. 51. 化合物5-bromo-2-methoxyphenyl acetate (14)的1H-NMR圖譜----------------------------------------------------------------- 103
Fig. 52. 化合物5-bromo-2-methoxyphenyl acetate (14)的13C-NMR圖譜----------------------------------------------------------------- 104
Fig. 53. 化合物5-bromo-2-methoxyphenol (15)的1H-NMR圖譜 ----------------------------------------------------------------------- 105
Fig. 54. 化合物5-bromo-2-methoxyphenol (15)的13C-NMR圖譜 ----------------------------------------------------------------------- 106
Fig. 55. 化合物2-(benzyloxy)-4-bromo-1-methoxybenzene (16)的H-NMR圖譜 ----------------------------------------------------- 107
Fig. 56. 化合物2-(benzyloxy)-4-bromo-1-methoxybenzene (16)的13C-NMR圖譜--------------------------------------------------- 108
Fig. 57. 化合物1-benzyl-4-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazole (17)的1H-NMR圖譜 ------------------------------------------ 109
Fig. 58. 化合物1-benzyl-4-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazole (17)的13C-NMR圖譜 --------------------------------------- 110
Fig. 59. 化合物1-benzyl-5-(3-(benzyloxy)-4-methoxyphenyl)-4- (3,4,5 -trimethoxyphenyl)-1H-1,2,3-triazole (18)的1H-NMR圖譜 --------------------------------------------------------------------- 111
Fig. 60. 化合物1-benzyl-5-(3-(benzyloxy)-4-methoxyphenyl)-4-(3,4,5- trimethoxyphenyl)-1H-1,2,3-triazole (18)的13C-NMR圖譜 --------------------------------------------------------------------- 112
Fig. 61. 化合物methyl-5-(1-benzyl-4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)-2-methoxybenzoate (19)的1H-NMR圖譜 ----------------------------------------------------------------------- 113
Fig. 62. 化合物methyl-5-(1-benzyl-4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)-2-methoxybenzoate (19)的13C-NMR圖譜 ----------------------------------------------------------------------- 114
Fig. 63. 化合物(5-(1-benzyl-4-(3,4,5-trimethoxyphenyl)-1H-1,2,3-tri-
azol-5-yl)-2-methoxyphenyl)methanol (20)的1H-NMR圖譜 ------------------------------------------------------------------------ 115
Fig. 64. 化合物(5-(1-benzyl-4-(3,4,5-trimethoxyphenyl)-1H-1,2,3-tri-
azol-5-yl)-2-methoxyphenyl)methanol (20)的13C-NMR圖譜------------------------------------------------------------------------ 116
Fig. 65. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl) phenol (21)的1H-NMR圖譜------------------- 117
Fig. 66. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl) phenol (21)的13C-NMR圖譜----------------- 118
Fig. 67. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl) phenol (21)的COSY圖譜----------------------- 119
Fig. 68. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl) phenol (21)的HMBC圖譜----------------------- 120
Fig. 69. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl) phenol (21)的HMQC圖譜----------------------- 121
Fig. 70. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl) phenol (21)的EI-MS圖譜---------------------- 122
Fig. 71. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl) phenol (21)的FTIR圖譜------------------------ 123
Fig. 72. 化合物methyl-2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-
1H-1,2,3-triazol-5-yl)benzoate (22)的1H-NMR圖譜------ 124
Fig. 73. 化合物methyl-2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-
1H-1,2,3-triazol-5-yl)benzoate (22)的13C-NMR圖譜----- 125
Fig. 74. 化合物methyl-2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-
1H-1,2,3-triazol-5-yl)benzoate (22)的COSY圖譜---------- 126
Fig. 75. 化合物methyl-2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-
1H-1,2,3-triazol-5-yl)benzoate (22)的HMBC圖譜--------- 127
Fig. 76. 化合物methyl-2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-
1H-1,2,3-triazol-5-yl)benzoate (22)的HMQC圖譜--------- 128
Fig. 77. 化合物methyl-2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-
1H-1,2,3-triazol-5-yl)benzoate (22)的EI-MS圖譜--------- 129
Fig. 78. 化合物methyl-2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-
1H-1,2,3-triazol-5-yl)benzoate (22)的FTIR圖譜------------ 130
Fig. 79. 化合物1-benzyl-5-(4-methoxy-3-methylphenyl)-4-(3,4,5-tri-
methoxyphenyl)-1H-1,2,3-triazole (23)的1H-NMR圖譜------131
Fig. 80. 化合物1-benzyl-5-(4-methoxy-3-methylphenyl)-4-(3,4,5-tri-
methoxyphenyl)-1H-1,2,3-triazole (23)的13C-NMR的圖譜-- 132
Fig. 81. 化合物1-benzyl-5-(4-methoxy-3-methylphenyl)-4-(3,4,5-tri-
methoxyphenyl)-1H-1,2,3-triazole (23)的COSY圖譜------- 133
Fig. 82. 化合物1-benzyl-5-(4-methoxy-3-methylphenyl)-4-(3,4,5-tri-
methoxyphenyl)-1H-1,2,3-triazole (23)的HMBC圖譜------ 134
Fig. 83. 化合物1-benzyl-5-(4-methoxy-3-methylphenyl)-4-(3,4,5-tri-
methoxyphenyl)-1H-1,2,3-triazole (23)的HMQC圖譜----- 135
Fig. 84. 化合物1-benzyl-5-(4-methoxy-3-methylphenyl)-4-(3,4,5-tri-
methoxyphenyl)-1H-1,2,3-triazole (23)的EI-MS圖譜------ 136
Fig. 85. 化合物1-benzyl-5-(4-methoxy-3-methylphenyl)-4-(3,4,5-tri-
methoxyphenyl)-1H-1,2,3-triazole (23)的FTIR圖譜------- 137
Fig. 86. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)benzoic acid (24)的1H-NMR圖譜--------------- 138
Fig. 87. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)benzoic acid (24)的13C-NMR圖譜-------------- 139
Fig. 88. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)benzoic acid (24)的COSY圖譜---------------- 140
Fig. 89. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)benzoic acid (24)的HMBC圖譜--------------- 141
Fig. 90. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)benzoic acid (24)的HMQC圖譜-------------- 142
Fig. 91. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)benzoic acid (24)的EI-MS圖譜---------------- 143
Fig. 92. 化合物2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)benzoic acid (24)的FTIR圖譜----------------- 144
Fig. 93. 化合物(2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)phenyl)methanol (25)的1H-NMR圖譜--------- 145
Fig. 94. 化合物(2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)phenyl)methanol (25)的13C-NMR圖譜-------- 146
Fig. 95. 化合物(2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)phenyl)methanol (25)的COSY圖譜------------ 147
Fig. 96. 化合物(2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)phenyl)methanol (25)的HMBC圖譜----------- 148
Fig. 97. 化合物(2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)phenyl)methanol (25)的HMQC圖譜---------- 149
Fig.98. 化合物(2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)phenyl)methanol (25)的EI-MS圖譜----------- 150
Fig.99. 化合物(2-methoxy-5-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3- triazol-5-yl)phenyl)methanol (25)的FTIR圖譜------------ 151
Fig. 100. 化合物1-benzyl-5-(naphthalen-2-yl)-4-(3,4,5-trimethoxy-
phenyl)-1H-1,2,3-triazole (26)的1H-NMR圖譜------------ 152
Fig.101. 化合物1-benzyl-5-(naphthalen-2-yl)-4-(3,4,5-trimethoxy-
phenyl)-1H-1,2,3-triazole (26)的13C-NMR圖譜------------- 153
Fig. 102. 化合物5-(naphthalen-2-yl)-4-(3,4,5-trimethoxyphenyl)-1H-
1,2,3-triazole (27)的1H-NMR圖譜--------------------------- 154
Fig.103. 化合物5-(naphthalen-2-yl)-4-(3,4,5-trimethoxyphenyl)-1H-
1,2,3-triazole (27)的13C-NMR圖譜-------------------------- 155
Fig.104. 化合物5-(naphthalen-2-yl)-4-(3,4,5-trimethoxyphenyl)-1H-
1,2,3-triazole (27)的COSY圖譜------------------------------- 156
Fig. 105. 化合物5-(naphthalen-2-yl)-4-(3,4,5-trimethoxyphenyl)-1H-
1,2,3-triazole (27)的HMBC圖譜------------------------------ 157
Fig.106. 化合物5-(naphthalen-2-yl)-4-(3,4,5-trimethoxyphenyl)-1H-
1,2,3-triazole (27)的HMQC圖譜---------------------------- 158
Fig.107. 化合物5-(naphthalen-2-yl)-4-(3,4,5-trimethoxyphenyl)-1H-
1,2,3-triazole (27)的EI-MS圖譜----------------------------- 159
Fig.108. 化合物5-(naphthalen-2-yl)-4-(3,4,5-trimethoxyphenyl)-1H-
1,2,3-triazole (27)的FTIR圖譜------------------------------- 160
Table 1. 化合物9、21 之1H和13C NMR數據(CDCl3) ------------- 51
Table 2. 化合物10、22之1H和13C NMR數據(CDCl3) ------------ 52
Table 3. 化合物24、27之1H和13C NMR數據(CDCl3) ------------ 53
Table 4. 化合物23、25之1H和13C NMR數據(CDCl3) ------------ 54
Table 5. Cytotoxicity of synthesized compounds in tumor cell lines ---- 55


陸 參考文獻
1.Pettit, G. R.; Cragg, G. M.; Herald, D. L.; Schmidt, J. M.; Lohavanijaya, P. Isolation and Structure of Combretastatin. Can. J. Chem. 1982, 60, 1374–1376.
2. Pettit, G. R.; Grealish M. P.; Herald, D. L.; Boyd, M. R.; Hamel,
E.;Pettit, R. K. Antineoplastic Agents. 443. Synthesis of the Cancer Cell Growth Inhibitor Hydroxyphenstatin and Its Sodium Diphosphate Prodrug. J. Med. Chem. 2000, 43, 2731–2737.
3.Petter, G. R.; Singh, S. B.; Boyd, M. R.; Hamel, E.; Pettit, R. K.; Schmidt, J. M.; Hogan, F. Antineoplastic Agents. 291. Isolation and Synthesis of Combretastatins A-4, A-5, and A-6. J. Med. Chem. 1995, 28, 1666–1672.
4.Pettit, G. R.; Rhodes, M. R.; Herald, D. L.; Hamel, E.; Schmidt, J. M.; Pettit, R. K. Antineoplastic agents. 445. Synthesis and Evaluation of Structural Modifications of (Z)- and (E)-Combretastatin A-4. J. Med. Chem. 2005, 48, 4087–4099.
5.McGown, A. T.; Fox, B. W. Differential cytotoxicity of combretastatins A1 and A4 in two daunorubicin-resistant P388 cell lines. Cancer Chemother. Pharmacol. 1990, 26, 79–81.
6.Pettit, G. R.; Grealish, M. P.; Jung, M. K.; Hamel, E.; Pettit, R. K.; Chapuis, J.-C.; Schmidt, J. M. Antimitotic Natural Products Combretastatin A-4 and Combretastatin A-2: Studies on the Mechanism of Their Inhibition of the Binding of Colchicine to Tubulin. J. Med. Chem. 2002, 45, 2534–2542.
7.Lin, C. M.; Singh S. B.; Chu, P S.; Dempcy, R. O.; Schmidt, J. M; Pettit, G. R.; Hamel, E. Interactions of Tubulin with Potent Natural and Synthetic Analogues of the Antimitotic Agent Combretastatin; A Structure-Activity Study. Mol. Pharmacol. 1988, 34, 200–208.
8.Chaplin, D. J.; Pettit, G. R.; Hill, S. A. Anti-vascular Approaches to Solid Tumour Therapy: Evaluation of Combretastatin A-4 Phosphate. Anticancer Res. 1999, 19, 189–195.
9.Grosios, K.; Holwell, S. E.; McGown, A. T.; Pettit, G. R.; Bibby, M. C. In Vivo and in Vitro Evaluation of Combretastatin A-4 and Its Sodium Phosphate Prodrug. Br. J. Cancer 1999, 81, 1318–1327.
10.Ohsumi, K.; Hatanaka, T.; Fujita, K.; Nakagawa, R.; Fukuda, Y.; Nihei, Y.; Suga, Y.; Morinaga, Y.; Akiyama, Y.; Tsuji, T. Synthesis and Antitumor Activity of Cis-Restricted Combretastatins: 5-Membered Heterocyclic Analogues. Bioorg. Med. Chem. Lett. 1998, 8, 3153–3158.
11.Wang, L.; Woods, K. W.; Li, Q.; Barr, K. J.; McCroskey, R. W.; Hannick, S. M.; Gherke, L.; Credo, R. B.; Hui, Y. H.; Marsh, K.; Warner, R.; Lee, J. Y.; Zielinski, N.; Frost, D.; Rosenberg, S. H.; Sham, H. L. Potent, Orally Active Heterocycle-Based Combretastatin A-4 Analogues: Synthesis, Structure-Activity Relationship, Pharmacokinetics, and in Vivo Antitumor Activity Evaluation. J. Med. Chem. 2002, 45, 1697–1711.
12.Kim, Y.; Nam, N.-H.; You, Y.-J.; Ahn, B.-Z. Synthesis and Cytotoxicity of 3,4-Diaryl-2(5H)-furanones. Bioorg. Med. Chem. Lett. 2002, 12, 719–722.
13.Wu, M.; Sun, Q.; Yang, C.; Chen, D. ; Ding, J.; Chen, Y.; Lin, L.; Xie, Y. Synthesis and Activity of Combretastatin A-4 Analogues: 1,2,3-Thiadiazoles as Potent Antitumor Agents. Bioorg. Med. Chem. Lett. 2007, 17, 869–873.
14.Sun, C.-M.; Lin, L.-G.; Yu, H.-J.; Cheng, C.-Y.; Tsai, Y.-C.; Chu, C.-W.; Din, Y.-H.; Chau, Y.-P.; Don, M.-J. Synthesis and Cytotoxic activities of 4,5-Diarylisoxazoles, Bioorg. Med. Chem. Lett. 2007, 17, 1078–1081.
15.Gupton, J. T.; Krumpe, K. E.; Burnham, B. S.; Dwornik, K. A.; Petrich, S. A.; Du, K. X.; Bruce, M. A.; Vu, P.; Vargas, M.; Keertikar, K. M.; Hosein, K. N.; Jones, C. R.; Sikorski, J. A. The Application of Disubstituted Vinylogous Iminium Salts and Related Synthons to the Regiocontrolled Preparation of Unsymmetrical 2,3,4-Trisubstituted Pyrroles. Tetrahedron 1998, 54, 5075–5088.
16.Pati, H. N.; Wicks, M.; Holt, H. L.; LeBlanc, R.; Weisbruch, P.; Forrest, L.; Lee, M. Heterocycl. Commun. 2005, 2, 117–120.
17.Prasad A.; Wim D.; Valery V. F.; Erik V. E. A Microwave-Assisted Click Chemistry Synthesis of 1,4-Disubstituted 1,2,3-Triazoles via a Copper(I)-Catalyzed Three-Component Reaction. Org. Lett. 2004, 6, 4223–4225.
18.Stepan C.; Natalia C.; Alexander S. D.; Vladimir G. Direct Pd-Catalyzed Arylation of 1,2,3-Triazoles. Org. Lett. 2007, 9, 2333–2336.
19.Ken S. F. Cyclization Pathways of a(Z)-Stilbene-Derived Bis(orthoquinonemonoketal). J. Org. Chem. 1997, 62, 4983–4990.
20.Mekhman S. Y.; Elena N. T. Solvent-Free Iodination of Arenes using Iodine–Silver Nitrate Combination. Synthetic Commun. 2007, 37, 1259–1265.
21.Lingjun Li.; Guisheng Z.; Anlian Z.; Lihe Z. A Convenient Preparation of 5-Iodo-1,4-disubstituted-1,2,3-triazole: Multicomponent One-Pot Reaction of Azide and Alkyne Mediated by CuI-NBS. J. Org. Chem. 2008, 73, 3630–3633.
22.Pranjal K. B.; Sreedevi N. K.; Rajesh G.; Sapna R.; Krishnan D. Enforcing Periodic Secondary Structures in Hybrid Peptides: A Novel Hybrid Foldamer Containing Periodic g-Turn Motifs. J. Org. Chem. 2007, 72, 636–639.


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