(3.80.6.131) 您好!臺灣時間:2021/05/14 02:37
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:張怡婷
研究生(外文):Yi-Ting Chang
論文名稱:雙環磺胺雜環類抗癌化合物之合成和結構與活性關係的研究
論文名稱(外文):Synthesis and Structure-Activity Relationships of Biphenyl-Sulfonamides Heterocycles as Anticancer Agents
指導教授:劉景平劉景平引用關係
指導教授(外文):Jing-Ping Liou
學位類別:碩士
校院名稱:臺北醫學大學
系所名稱:藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:中文
論文頁數:157
中文關鍵詞:雙環磺胺雜環抗癌結構與活性關係
外文關鍵詞:Biphenyl-Sulfonamides HeterocyclesAnticancer Agents
相關次數:
  • 被引用被引用:0
  • 點閱點閱:142
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
以生物等效性的概念為基礎,先前已將N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4- methoxybenzene- sulfonamide(ABT-751)此基本骨架進行修飾,合成出兩個新系列7-苯胺基-6-氮基吲哚-1-磺胺和7-苯基-6-氮基吲哚-1-磺胺且均具抗增生活性之化合物。ABT-751是透過和微小管上的秋水仙素鹼鍵結位置鍵結產生作用的口服有活性的抗癌化合物。現正在美國進行人體臨床試驗第二期。在先前的研究中發現 7-苯基-6-氮基吲哚-1-磺胺類衍生物的活性較7-苯胺基-6-氮基吲哚-1-磺胺類衍生物的活性強,於是更進一步研究其抗增生機轉與結構之間關係,另合成了7-苯基吲哚-1-磺胺和7-苯基二氫吲哚-1-磺胺。7-苯基吲哚-1-磺胺類衍生物是以1-溴基-2-硝基苯與乙烯基鎂溴反應後與4-甲氧基-磺基氯苯反應得到7-溴基吲哚-1-磺胺。七號位碳上溴基與各種苯硼酸進行鈴木偶合反應即可得到7-苯基吲哚-1-磺胺。7-苯基二氫吲哚-1-磺胺類衍生物是將1-溴基-2-硝基苯與乙烯基鎂溴反應後得到之7-溴基吲哚以氰基硼氫化鈉還原後與4-甲氧基-磺基氯苯反應得到7-溴基二氫吲哚-1-磺胺。七號位碳上溴基再與各種苯硼酸進行鈴木偶合反應得到7-苯基二氫吲哚-1-磺胺。化合物1, 2, 4, 5, 9, 11, 12, 14, 15, 23及24表現出強效抗癌活性,IC50 在15-50 nM之間。而其結構與活性的關係顯示7位碳上接有拉電子基之苯環或五員、六員雜環皆可增加其活性,但真正之機轉仍待進一步確立。
Two novel series of 7-anilino-6-azaindole-1-sulfonamides and 7-aryl-6- azaindole-1-sulfonamides based on N-[2-[(4-hydroxyphenyl) amino]-3- pyridinyl]-4-methoxybenzenesulfonamide (ABT-751) as a template were synthesized as potent antiproliferative agents. ABT-751 is an orally-active anticancer agent acting through the binding with the colchicine binding site on the tubulin. It is now undergoing human clinical trial. Based on the more potent antiproliferative activity of 7-aryl-6-azaindole-1-sulfonamides, another two novel series of 7- arylindole-1-sulfonamides and 7-arylindoline-1-sulfonamides were synthesized. The synthesis of 7-aryl-6-azaindole-1-sulfonamide derivatives started from 2-bromo-3-nitropyridine, which was subjected to the vinyl magnesium bromide to give 7-bromo-6-azaindole, treated with 4-methoxybenzenesulfonyl chloride to afford the 6-azaindole -1-sulfonamides. A Suzuki reaction at 7-position, utilizing the 7-bromo -6-azaindole was treated with a variety of phenylboric acid to give the designed 7-aryl substituted 6-azaindoles. 7-arylindole-1-sulfonamides and 7-arylindoline-1-sulfonamide derivatives were prepared started from 1-bromo-2- nitrobenzene by the same procedure. Three types of core structure analogous, for example, 7-aryl-6-azaindoles (20-24), 7-arylindoles (18-19) and 7-arylindolines (1-17) were evaluated their antiproliferative activity against oral epidermoid carcinoma KB cells. In the preliminary data, compounds 1, 2, 4, 5, 9, 11, 12, 14, 15, 23, and 24 demonstrate substantial activity with IC50 values ranging from 15-50 nM. Structure- activity relationship information revealed that 7-aryl-6- azaindole-1- sulfonamide and 7-arylindoline-1-sulfonamide derivatives were more potent than 7-arylindole-1-sulfonamide derivatives. These findings have encouraged us to extensively explore these two novel sulfonamides and further investigate their mode of actions and mechanisms.
目錄 1
附表目錄 5
附圖目錄 6
中文摘要 10
英文摘要 12
壹、緒論 14
一、前言 14
二、化學治療藥物3 17
三、微管與細胞增殖週期 29
四、作用在微管之抗癌藥物9 33
貳、研究背景 38
参、研究目的 44
肆、結果及討論 45
一、化學合成 45
二、生物活性(KB cell line) 55
三、結構與活性(Structure-Activity Relationship) 58
伍、結論 59
陸、實驗 60
一、實驗儀器 60
二、試藥與試劑 61
三、合成步驟 64
7-(3,4-Difluorophenyl)-1-(4-methoxyphenylsulfonyl)indoline (1) 64
7-(4-Hydroxyphenyl)-1-(4-methoxyphenylsulfonyl)indoline (2) 65
7-(4-Methoxyphenyl)-1-(4-methoxyphenylsulfonyl)indoline (3) 66
7-(4-Fluorophenyl)-1-(4-methoxyphenylsulfonyl)indoline (4) 67
7-(Furanyl-2-yl)-1-(4-methoxyphenylsulfonyl)indoline (5) 68
1-(4-Methoxyphenylsulfonyl)-7-(thiophen-2-yl)indoline (6) 69
7-(4-(N,N-dimethylamino)phenyl)-1-(4-methoxyphenylsulfonyl)indoline (7) 70
1-(4-Methoxyphenylsulfonyl)-7-(3,4,5-trimethoxyphenyl)indoline (8) 71
7-(4-Chlorophenyl)-1-(4-methoxyphenylsulfonyl)indoline (9) 72
1-(4-Methoxyphenylsulfonyl)-7-(4-(trifluoromethyl)phenyl)indoline (10) 73
7-(3-Fluorophenyl)-1-(4-methoxyphenylsulfonyl)indoline (11) 74
1-(4-Methoxyphenylsulfonyl)-7-phenylindoline (12) 75
1-(4-Methoxyphenylsulfonyl)-7-(3-pyridinyl)indoline (13) 76
1-(4-Methoxyphenylsulfonyl)-7-(4-nitrophenyl)indoline (14) 77
1-(4-Methoxyphenylsulfonyl)-7-(4-pyridinyl)indoline (15) 78
7-(4-Fluorophenyl)-1-(4-sulfonamidephenylsulfonyl)indoline (16) 79
7-(Pyridine-4-yl)-1-(4-sulfonamidephenylsulfonyl)indoline (17) 80
7-(4-Fluorophenyl)-1-(4- methoxyphenylsulfonyl)indole (18) 81
7-(4-Cyanophenyl)-1-(4- methoxyphenylsulfonyl)indole (19) 82
7-(4-Hydrophenyl)-1-(4-methoxyphenylsulfonyl)-6-azaindole (20) 83
1-(4-Methoxyphenylsulfonyl)-7-(4-pyridinyl)-6-azaindole (21) 84
1-(4-Methoxyphenylsulfonyl)-7-(4-nitrophenyl)-6-azaindole (22) 85
7-(2-Furanyl)-1-(4-methoxyphenylsulfonyl)-6-azaindole (23) 86
1-(4-Methoxyphenylsulfonyl)-7-(2-thiophenyl)-6-azaindole (24) 87
7-Bromo-1-(4-methoxyphenylsulfonyl)indoline (25) 88
7-Bromo-1-(4-sulfonamidephenylsulfonyl)indoline (26) 89
7-Bromo-1-(4-methoxyphenylsulfonyl)indole (27) 90
7-Bromo-1(4-methoxyphenylsulfonyl)-6-aza-indole (28) 91
7-Bromoindole (29) 92
7-Bromo-6-azaindole (30) 93
四、生物活性 94
柒、參考文獻 95
捌、附圖部分 100

附表目錄
表一、民國九十五年十大死因2 15
表二、化合物1-24抑制KB細胞株生長之活性 55

附圖目錄
圖一、民國九十五年臺灣地區主要死因死亡率趨勢圖2 16
圖二、細胞週期8 30
圖三、細胞週期 31
圖四、微小管的構造與動態性5 32
圖五、抗有絲分裂藥物於微小管的結合部位3 36
圖六、以苯磺醯胺(arylsulfonamide)為結構的藥物 39
圖七、ABT-751衍生化合物 43
圖八、化合物1的氫核磁共振圖 101
圖九、化合物1的碳核磁共振圖 102
圖十、化合物1的質譜圖 103
圖十一、化合物2的氫核磁共振圖 104
圖十二、化合物2的碳核磁共振圖 105
圖十三、化合物2的質譜圖 106
圖十四、化合物3的氫核磁共振圖 107
圖十五、化合物3的碳核磁共振圖 108
圖十六、化合物3的質譜圖 109
圖十七、化合物4的氫核磁共振圖 110
圖十八、化合物4的質譜圖 111
圖十九、化合物5的氫核磁共振圖 112
圖二十、化合物5的質譜圖 113
圖二十一、化合物6的氫核磁共振圖 114
圖二十二、化合物6的質譜圖 115
圖二十三、化合物7的氫核磁共振圖 116
圖二十四、化合物7的質譜圖 117
圖二十五、化合物8的氫核磁共振圖 118
圖二十六、化合物8的質譜圖 119
圖二十七、化合物9的氫核磁共振圖 120
圖二十八、化合物9的質譜圖 121
圖二十九、化合物10的氫核磁共振圖 122
圖三十、化合物10的質譜圖 123
圖三十一、化合物11的氫核磁共振圖 124
圖三十二、化合物11的質譜圖 125
圖三十三、化合物12的氫核磁共振圖 126
圖三十四、化合物12的質譜圖 127
圖三十五、化合物13的氫核磁共振圖 128
圖三十六、化合物13的質譜圖 129
圖三十七、化合物14的氫核磁共振圖 130
圖三十八、化合物14的質譜圖 131
圖三十九、化合物15的氫核磁共振圖 132
圖四十、化合物15的質譜圖 133
圖四十一、化合物16的氫核磁共振圖 134
圖四十二、化合物16的碳核磁共振圖 135
圖四十三、化合物16的質譜圖 136
圖四十四、化合物17的氫核磁共振圖 137
圖四十五、化合物17的質譜圖 138
圖四十六、化合物18的氫核磁共振圖 139
圖四十七、化合物18的碳核磁共振圖 140
圖四十八、化合物18的質譜圖 141
圖四十九、化合物19的質譜圖 142
圖五十、化合物20的氫核磁共振圖 143
圖五十一、化合物20的質譜圖 144
圖五十二、化合物21的氫核磁共振圖 145
圖五十三、化合物21的質譜圖 146
圖五十四、化合物22的氫核磁共振圖 147
圖五十五、化合物22的質譜圖 148
圖五十六、化合物23的氫核磁共振圖 149
圖五十七、化合物23的質譜圖 150
圖五十八、化合物24的氫核磁共振圖 151
圖五十九、化合物24的質譜圖 152
圖六十、化合物25的氫核磁共振圖 153
圖六十一、化合物26的氫核磁共振圖 154
圖六十二、化合物27的氫核磁共振圖 155
圖六十三、化合物4 的晶體結構圖 156
圖六十四、化合物15 的晶體結構圖 157
1.http://www.who.int/mediacentre/factsheets/fs297/en/index.html.
2.http://www.doh.gov.tw/statistic/index.htm.
3.Jordan, M. A.; Wilson, L. Microtubules as a target for anticancer drugs. Nat. Rev. Cancer 2004, 4, 253-265.
4.Chen, W.; Zhang, D. Kinetochore fibre dynamics outside the context of the spindle during anaphase. Nat. Cell Biol. 2004, 6, 227-231.
5.Akhmanova, A.; Steinmetz, M. O. Tracking the ends: a dynamic protein network controls the fate of microtubule tips. Nat. Rev. Mol. Cell Bio. 2008, 9, 309-322.
6.Jordan, A.; Hadfield, J. A.; Lawrence, N. J.; McGown, A. T. Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med. Res. Rev. 1998, 18, 259-296.
7.Dinu, C. Z.; Chrisey, D. B.; Diez, S.; Howard, J. Cellular motors for molecular manufacturing. Anat. Rec. 2007, 290, 1203-1212.
8.http://fig.cox.miami.edu/~cmallery/255/255mitos/255division.htm.
9.Mahindroo, N.; Liou, J. P.; Chang, J. Y.; Hsieh, H. P. Antitubulin Agents for the Treatment of Cancer - a Medicinal Chemistry Update. Expert Opin. Ther. Patents 2006, 16, 647-691.
10.Eckhardt, S. Recent progress in the development of anticancer agents. Cur. Med. Chem. 2002, 2, 419-439.
11.Davis, P. D.; Dougherty, G. J.; Blakey, D. C.; Galbraith, S. M.; Tozer, G. M.; Holder, A. L.; Naylor, M. A.; Nolan, J.; Stratford, M. R.; Chaplin, D. J.; Hill, S. A. ZD6126: a novel vascular-targeting agent that causes selective destruction of tumor vasculature. Cancer Res. 2002, 62, 7247-7253.
12.Chaplin, D. J.; Horsman, M. R.; Siemann, D. W. Current development status of small-molecule vascular disrupting agents. Curr. Opin. Investig Drugs 2006, 7, 522-528.
13.Drews, J. Drug discovery: a historical perspective. Science 2000, 287, 1960-1964.
14.Supuran, C. T.; Scozzafava, A. Carbonic Anhydrase Inhibitors and their Therapeutic Potential. Exp. Opin.Ther. Patents 2000, 10, 575-600.
15.Maren, T. H. Relatons between structure and biological activity of sulfonamides. Annu. Rev. Pharmacol Toxicol 1976, 16, 309-327.
16.Wouters, J.; Michaux, C.; Durant, F.; Dogne, J. M.; Delarge, J.; Masereel, B. Isosterism among analogues of torasemide: conformational, electronic and lipophilic properties. Eur. J. Med. Chem. 2000, 35, 923-929.
17.Flores Toque, H. A.; Priviero, F. B. M.; Teixeira, C. E.; Perissutti, E.; Fiorino, F.; Severino, B.; Frecentese, F.; Lorenzetti, R.; Baracat, J. S.; Santagada, V.; Caliendo, G.; Antunes, E.; De Nucci, G. Synthesis and Pharmacological Evaluations of Sildenafil Analogues for Treatment of Erectile Dysfunction. J. Med. Chem. 2008, 51, 2807-2815.
18.Habeeb, A. G.; Rao, P. N. P.; Knaus, E. E. Design and Synthesis of Celecoxib and Rofecoxib Analogues as Selective Cyclooxygenase-2 (COX-2) Inhibitors: Replacement of Sulfonamide and Methylsulfonyl Pharmacophores by an Azido Bioisostere. J. Med. Chem. 2001, 44, 3039-3042.
19.Szabo, G.; Fischer, J.; Kis-Varga, A.; Gyires, K. New Celecoxib Derivatives as Anti-Inflammatory Agents. J. Med. Chem. 2008, 51, 142-147.
20.Weber, A.; Casini, A.; Heine, A.; Kuhn, D.; Supuran, C. T.; Scozzafava, A.; Klebe, G. Unexpected Nanomolar Inhibition of Carbonic Anhydrase by COX-2-Selective Celecoxib: New Pharmacological Opportunities Due to Related Binding Site Recognition. J. Med. Chem. 2004, 47, 550-557.
21.Wilkinson, B. L.; Bornaghi, L. F.; Wright, A. D.; Houston, T. A.; Poulsen, S.-A. Anti-mycobacterial activity of a bis-sulfonamide. Bioorg. Med. Chem. Lett. 2007, 17, 1355-1357.
22.Josien, H.; Bara, T.; Rajagopalan, M.; Asberom, T.; Clader, J. W.; Favreau, L.; Greenlee, W. J.; Hyde, L. A.; Nomeir, A. A.; Parker, E. M.; Pissarnitski, D. A.; Song, L.; Wong, G. T.; Zhang, L.; Zhang, Q.; Zhao, Z. Small conformationally restricted piperidine N-arylsulfonamides as orally active g-secretase inhibitors. Bioorg. Med. Chem. Lett. 2007, 17, 5330-5335.
23.Fuwa, H.; Hiromoto, K.; Takahashi, Y.; Yokoshima, S.; Kan, T.; Fukuyama, T.; Iwatsubo, T.; Tomita, T.; Natsugari, H. Synthesis of biotinylated photoaffinity probes based on arylsulfonamide g-secretase inhibitors. Bioorg. Med. Chem. Lett.2006, 16, 4184-4189.
24.Link, J. T.; Sorensen, B.; Patel, J.; Grynfarb, M.; Goos-Nilsson, A.; Wang, J.; Fung, S.; Wilcox, D.; Zinker, B.; Nguyen, P.; Hickman, B.; Schmidt, J. M.; Swanson, S.; Tian, Z.; Reisch, T. J.; Rotert, G.; Du, J.; Lane, B.; Von Geldern, T. W.; Jacobson, P. B. Antidiabetic Activity of Passive Nonsteroidal Glucocorticoid Receptor Modulators. J. Med. Chem. 2005, 48, 5295-5304.
25.Sawa, M.; Mizuno, K.; Harada, H.; Tateishi, H.; Arai, Y.; Suzuki, S.; Oue, M.; Tsujiuchi, H.; Furutani, Y.; Kato, S. Tryptamine-based human b3-adrenergic receptor agonists. Part 3: Improved oral bioavailability via modification of the sulfonamide moiety. Bioorg. Med. Chem. Lett.2005, 15, 1061-1064.
26.Senger, S.; Convery, M. A.; Chan, C.; Watson, N. S. Arylsulfonamides: A study of the relationship between activity and conformational preferences for a series of factor Xa inhibitors. Bioorg. Med. Chem. Lett.2006, 16, 5731-5735.
27.Kirby, S.; Gertler, S. Z.; Mason, W.; Watling, C.; Forsyth, P.; Aniagolu, J.; Stagg, R.; Wright, M.; Powers, J.; Eisenhauer, E. A. Phase 2 study of T138067-sodium in patients with malignant glioma: Trial of the National Cancer Institute of Canada Clinical Trials Group. Neuro Oncol. 2005, 7, 183-188.
28.Takagi, M.; Honmura, T.; Watanabe, S.; Yamaguchi, R.; Nogawa, M.; Nishimura, I.; Katoh, F.; Matsuda, M.; Hidaka, H. In vivo antitumor activity of a novel sulfonamide, HMN-214, against human tumor xenografts in mice and the spectrum of cytotoxicity of its active metabolite, HMN-176. Invest. New Drugs 2003, 21, 387-399.
29.Garland, L. L.; Taylor, C.; Pilkington, D. L.; Cohen, J. L.; Von Hoff, D. D. A phase I pharmacokinetic study of HMN-214, a novel oral stilbene derivative with polo-like kinase-1-interacting properties, in patients with advanced solid tumors. Clin. Cancer Res. 2006, 12, 5182-5189.
30.Owa, T.; Yoshino, H.; Okauchi, T.; Yoshimatsu, K.; Ozawa, Y.; Sugi, N. H.; Nagasu, T.; Koyanagi, N.; Kitoh, K. Discovery of novel antitumor sulfonamides targeting G1 phase of the cell cycle. J. Med. Chem. 1999, 42, 3789-3799.
31.Supuran, C. T. Indisulam: an anticancer sulfonamide in clinical development. Expert Opin. Investig. Drugs 2003, 12, 283-287.
32.Talbot, D. C.; von Pawel, J.; Cattell, E.; Yule, S. M.; Johnston, C.; Zandvliet, A. S.; Huitema, A. D.; Norbury, C. J.; Ellis, P.; Bosquee, L.; Reck, M. A randomized phase II pharmacokinetic and pharmacodynamic study of indisulam as second-line therapy in patients with advanced non-small cell lung cancer. Clin. Cancer Res. 2007, 13, 1816-1822.
33.Yoshino, H.; Ueda, N.; Niijima, J.; Sugumi, H.; Kotake, Y.; Koyanagi, N.; Yoshimatsu, K.; Asada, M.; Watanabe, T.; Nagasu, T.; et al. Novel sulfonamides as potential, systemically active antitumor agents. J. Med. Chem. 1992, 35, 2496-2497.
34.Yamamoto, K.; Noda, K.; Yoshimura, A.; Fukuoka, M.; Furuse, K.; Niitani, H. Phase I study of E7010. Cancer Chemother Pharmacol 1998, 42, 127-134.
35.Hande, K. R.; Hagey, A.; Berlin, J.; Cai, Y.; Meek, K.; Kobayashi, H.; Lockhart, A. C.; Medina, D.; Sosman, J.; Gordon, G. B.; Rothenberg, M. L. The pharmacokinetics and safety of ABT-751, a novel, orally bioavailable sulfonamide antimitotic agent: results of a phase 1 study. Clin. Cancer Res. 2006, 12, 2834-2840.
36.http://clinicaltrials.gov/ct/search;jsessionid=9A28592ABE12A3415D802076DEA08FE4?term=ABT-751.
37.Segreti, J. A.; Polakowski, J. S.; Koch, K. A.; Marsh, K. C.; Bauch, J. L.; Rosenberg, S. H.; Sham, H. L.; Cox, B. F.; Reinhart, G. A. Tumor selective antivascular effects of the novel antimitotic compound ABT-751: an in vivo rat regional hemodynamic study. Cancer Chemother Pharmacol 2004, 54, 273-281.
38.Gwaltney, S. L., 2nd; Imade, H. M.; Li, Q.; Gehrke, L.; Credo, R. B.; Warner, R. B.; Lee, J. Y.; Kovar, P.; Frost, D.; Ng, S. C.; Sham, H. L. Novel sulfonate derivatives: potent antimitotic agents. Bioorg. Med. Chem. Lett. 2001, 11, 1671-1673.
39.Chang, J. Y.; Hsieh, H. P.; Chang, C. Y.; Hsu, K. S.; Chiang, Y. F.; Chen, C. M.; Kuo, C. C.; Liou, J. P. 7-Aroyl-aminoindoline-1-sulfonamides as a novel class of potent antitubulin agents. J. Med. Chem. 2006, 49, 6656-6659.
40.Lebegue, N.; Gallet, S.; Flouquet, N.; Carato, P.; Pfeiffer, B.; Renard, P.; Leonce, S.; Pierre, A.; Chavatte, P.; Berthelot, P. Novel benzopyridothiadiazepines as potential active antitumor agents. J. Med. Chem. 2005, 48, 7363-7373.
41.Zhang, Z.; Yang, Z.; Meanwell, N. A.; Kadow, J. F.; Wang, T. A general method for the preparation of 4- and 6-azaindoles. J. Org. Chem. 2002, 67, 2345-2347.
42.Joule, J. A.; Joule, J.; Mills, K. Heterocyclic Chemistry. 4 ed.; Blackwell Science Oxford, 2000; p 361.
43.Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Couling Reaction of Organoboron Compounds. Chem. Rev. 1995, 95, 2457-2483.
44.Gellibert, F.; de Gouville, A. C.; Woolven, J.; Mathews, N.; Nguyen, V. L.; Bertho-Ruault, C.; Patikis, A.; Grygielko, E. T.; Laping, N. J.; Huet, S. Discovery of 4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-
N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388): a potent, selective, and orally active transforming growth factor-beta type I receptor inhibitor. J. Med. Chem. 2006, 49, 2210-2221.
45.Prieto, M.; Zurita, E.; Rosa, E.; Munoz, L.; Lloyd-Williams, P.; Giralt, E. Arylboronic acids and arylpinacolboronate esters in Suzuki coupling reactions involving indoles. Partner role swapping and heterocycle protection. J. Org. Chem. 2004, 69, 6812-6820.
46.Finlay, G. J.; Baguley, B. C.; Wilson, W. R. A semiautomated microculture method for investigating growth inhibitory effects of cytotoxic compounds on exponentially growing carcinoma cells. Anal. Biochem. 1984, 139, 272-277.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文
 
無相關期刊
 
1. 芳醯喹啉與苯基喹啉為新穎微管蛋白聚合抑制劑之合成和結構與活性關係
2. 含氮之[6,5]雜環類緣物之合成與抗癌活性研究
3. N-苯胺和雙環系統磺胺類緣物之合成與抗癌活性之研究
4. 5,6,7-trimethoxyindoles和5,6,7-trimethoxy-2-oxoindoles抗癌化合物之合成和結構活性關係研究
5. 壹、N1-芳香基和苯甲基-4,5,6-三甲氧基吲哚為新穎微管蛋白聚合抑制劑之合成和結構與活性關係的研究貳、開發苯磺醯取代之5-6騈環雜環為新穎組蛋白去乙醯酶抑制劑的研究
6. 合成及結構與活性關係之1-磺基苯-6氮基吲哚類有效抗癌化合物
7. 2-胺基與2’-胺基Combretastatins衍生物做為強效抗有絲分裂劑
8. 壹、設計與合成2-胺基-3,4,5-三甲氧基二苯甲酮作為強效微管蛋白聚合抑制劑貳、設計與合成聯苯基苯磺醯胺衍生物作為新穎抗癌試劑之合成和結構與活性關係研究參、設計與合成2-胺基苯醯胺之苯磺醯胺衍生物作為強效抗癌試劑
9. 合成二羥苯基衍生物作為新穎抗癌化合物
10. 我國Losartan生體相等性試驗之回溯性研究
11. Warfarin療效與安全性評估
12. 比較兩非麥角多巴胺受體致效劑的小型第四期臨床試驗:帕金森氏症病人由力必平劑量逐步調整為樂伯克之評估
13. 雙效類澱粉胜肽凝聚調控劑作為潛能的阿茲海默症治療
14. I、開發以Lovastatin為基礎之羥基醯胺作為選擇性組蛋白去乙醯酶抑制劑;II、黃酮類Hispidulin之全合成研究
15. 含有反式二苯乙烯發色團的雙偶極有機材料應用於染料敏化太陽能電池
 
系統版面圖檔 系統版面圖檔