論文目次 |
中文摘要 ............................................................................................................. i
英文摘要 ............................................................................................................ ii
謝誌 ................................................................................................................... iii
目錄 ................................................................................................................... iv
圖目錄 .............................................................................................................. xv
表目錄 ............................................................................................................. xvi縮寫對照表...................................................................................................... xvii
一、 緒 論(Introduction).............................................................................. 1
二、 結 果(Results)....................................................................................... 8
2-1 製備1-Adamantyl Isocyanate (2)化合物 …….....………..……… 8
2-2 合成含矽保護基Adenosine–Amantadine與
Vidarabine–Amantadine共軛化合物 (9–11) ...…………..……... 8
2-3 合成含矽保護基Guanosine–Amantadine與
Acyclovir–Amantadine共軛化合物 (18–20) ...……....….....….. 13
2-4 合成含矽保護基Cytidine–Amantadine與
Cytarabine–Amantadine共軛化合物 (27–29) ............................ 14
2-5 合成含矽保護基Ribavirin–Amantadine共軛化合物 (32) ….… 16
2-6 合成Nucleoside–Amantadine脲鍵化合物 (33–42) ………….... 16
三、 討 論 (Discussion) ............................................................................... 18
3-1 探討「腺苷」與「阿糖胞苷」在鹼性條件下的反應性差異 ... 18
3-2 探討合成共軛化合物之最佳試劑 .............................................. 19
3-3 探討目標產物抑制「腸病毒71型」的活性表現 .................... 20
3-4 探討合成目標化合物時去保護的合成步驟 .............................. 23
3-5 探討Cytarabine–Amantadine Conjugate的反應位置
..與結構確定 ..……………………………………………………. 24
3-6 利用1H NMR光譜鑑定共軛化合物的位向 ............................... 26
3-7 利用UV-VIS測定脲鍵化合物33、34與41之水溶性 ................ 26
3-8 利用UV-VIS測定脲鍵化合物33、34與41之脂溶性 ................ 28
四、 結 論(Conclusion)….......................................................................... 31
五、 實 驗 部 分(Experimental Section)…............................................. 32
1-Adamantyl isocyanate (2) ...……..……………………………..……. 33
3’,5’-Di-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-
deoxyadenosine (9) ...………….………………………….……...... 34
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-
adenosine (10) ...………………………………...………………… 35
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-9-β-D-
arabinofuranosyladenine (11) ...………………………….………... 36
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N3-adamantylcarbamoyl-1-
(β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide (32) ....….… 37
3’,5’-Di-O-(tert-butyldimethylsilyl)-N2-adamantylcarbamoyl-
deoxyguanosine (18) ...…………………..…………….………….. 38
N2-Adamantylcarbamoyl-9-[2’-(tert-butyldimethylsilyloxy)-
ethoxymethyl]guanine (20) ...……………….......………....……… 39
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N2-adamantylcarbamoyl-
guanosine (19) ...…………………..……………….……………… 40
3’,5’-Di-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyl-
deoxycytidine (27) ...…………………..………………………….. 41
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyl-
cytidine (28) ...…………………..……………….……...………… 42
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyl-1-β-D-
arabinofuranosylcytosine (29) ...……………………..……………. 43
N6-Adamantylcarbamoyldeoxyadenosine (33) ...…..….......................... 44
N6-Adamantylcarbamoyladenosine (34) ..…….....…………...………... 45
N6-Adamantylcarbamoyl-9-β-D-arabinofuranosyladenine (35) ..…........ 46
N2-Adamantylcarbamoyldeoxyguanosine (36) ...…..…..…..……….…. 46
N2-Adamantylcarbamoylguanosine (37) ..…..…...…………...………... 47
N2-Adamantylcarbamoyl-9-[(2-hydroxyethoxy)methyl]guanine (38) .... 48
N4-Adamantylcarbamoyldeoxycytidine (39) .......…............................... 49
N4-Adamantylcarbamoylcytidine (40) ...…..…....................................... 50
N4-Adamantylcarbamoyl-1-β-D-arabinofuranosylcytosine (41) ............. 51
N3-Adamantylcarbamoyl-1-(β-D-ribofuranosyl)-1H-1,2,4-triazole-3-
carboxamide (42) ....…………………………………….....……… 51
六、 參 考 文 獻(References)……............................................................ 53
七、 光 譜 ...................................................................................................... 60
3’,5’-Di-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-
deoxyadenosine (9) 1H NMR spectrum ...………………..……..…. 62
3’,5’-Di-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-
deoxyadenosine (9) 13C NMR spectrum ...……..…….....…………. 62
3’,5’-Di-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-
deoxyadenosine (9) IR spectrum ...………………...….………..…. 63
3’,5’-Di-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-
deoxyadenosine (9) HPLC chromatogram ….…………...……..…. 63
3’,5’-Di-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-
deoxyadenosine (9) UV spectrum ….……………...….………..…. 64
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-
adenosine (10) 1H NMR spectrum ...………….…………......……. 64
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-
adenosine (10) 13C NMR spectrum ...………………..……………. 65
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-
adenosine (10) IR spectrum ...………...……….……………….…. 65
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-
adenosine (10) HPLC chromatogram ...………...…….……..……. 66
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-
adenosine (10) UV spectrum ...………...……..……………..……. 66
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-9-β-D-
arabinofuranosyladenine (11) 1H NMR spectrum ...………..…..…. 67
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-9-β-D-
arabinofuranosyladenine (11) 13C NMR spectrum ...………...……. 67
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-9-β-D-
arabinofuranosyladenine (11) IR spectrum ...………….….………. 68
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-9-β-D-
arabinofuranosyladenine (11) HPLC chromatogram ...…...………. 68
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N6-adamantylcarbamoyl-9-β-D-
arabinofuranosyladenine (11) UV spectrum ...………....….………. 69
3’,5’-Di-O-(tert-butyldimethylsilyl)-N2-adamantylcarbamoyldeoxy-
guanosine (18) 1H NMR spectrum ....…….………..…...…………. 69
3’,5’-Di-O-(tert-butyldimethylsilyl)-N2-adamantylcarbamoyldeoxy-
guanosine (18) 13C NMR spectrum ...…………….….....…………. 70
3’,5’-Di-O-(tert-butyldimethylsilyl)-N2-adamantylcarbamoyldeoxy-
guanosine (18) IR spectrum ...………….………….……...………. 70
3’,5’-Di-O-(tert-butyldimethylsilyl)-N2-adamantylcarbamoyldeoxy-
guanosine (18) HPLC chromatogram ...…..….…….……...………. 71
3’,5’-Di-O-(tert-butyldimethylsilyl)-N2-adamantylcarbamoyldeoxy-
guanosine (18) UV spectrum ...…..……..………….……...………. 71
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N2-adamantylcarbamoyl-
guanosine (19) 1H NMR spectrum ...………….…..………………. 72
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N2-adamantylcarbamoyl-
guanosine (19) 13C NMR spectrum ...……………...…...…………. 72
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N2-adamantylcarbamoyl-
guanosine (19) IR spectrum ...………….……..……..……………. 73
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N2-adamantylcarbamoyl-
guanosine (19) HPLC chromatogram ...……...……....……………. 73
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N2-adamantylcarbamoyl-
guanosine (19) UV spectrum ...……...………...……..……………. 74
N2-Adamantylcarbamoyl-9-[2’-(tert-butyldimethylsilyloxy)ethoxy-
methyl]guanine (20) 1H NMR spectrum ...……...................…...…. 74
N2-Adamantylcarbamoyl-9-[2’-(tert-butyldimethylsilyloxy)ethoxy-
methyl]guanine (20) 13C NMR spectrum ...….……………………. 75
N2-Adamantylcarbamoyl-9-[2’-(tert-butyldimethylsilyloxy)ethoxy-
methyl]guanine (20) IR spectrum ...…………...….………………. 75
N2-Adamantylcarbamoyl-9-[2’-(tert-butyldimethylsilyloxy)ethoxy-
methyl]guanine (20) HPLC chromatogram ...…….....….…………. 76
N2-Adamantylcarbamoyl-9-[2’-(tert-butyldimethylsilyloxy)ethoxy-
methyl]guanine (20) UV spectrum ...…….....……..………………. 76
3’,5’-Di-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyldeoxy-
cytidine (27) 1H NMR spectrum ....…….………..…...…...………. 77
3’,5’-Di-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyldeoxy-
cytidine (27) 13C NMR spectrum ...…………….….....….…..……. 77
3’,5’-Di-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyldeoxy-
cytidine (27) IR spectrum ...………….………….……...…………. 78
3’,5’-Di-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyldeoxy-
cytidine (27) HPLC chromatogram ...………...………...…………. 78
3’,5’-Di-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyldeoxy-
cytidine (27) UV spectrum ...…………...……….……...…………. 79
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyl-
cytidine (28) 1H NMR spectrum ...………….…..…………...……. 79
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyl-
cytidine (28) 13C NMR spectrum ...……………...…...…...………. 80
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyl-
cytidine (28) IR spectrum ...………….……..……..………………. 80
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyl-
cytidine (28) HPLC chromatogram ...…..….……...………………. 81
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyl-
cytidine (28) UV spectrum …...…..….……..……..………………. 81
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyl-1-β-D-
arabinofuranosylcytosine (29) 1H NMR spectrum ...…….……..…. 82
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyl-1-β-D-
arabinofuranosylcytosine (29) 13C NMR spectrum ...……..………. 82
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyl-1-β-D-
arabinofuranosylcytosine (29) IR spectrum ...……………….……. 83
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyl-1-β-D-
arabinofuranosylcytosine (29) HPLC chromatogram ...……......…. 83
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N4-adamantylcarbamoyl-1-β-D-
arabinofuranosylcytosine (29) UV spectrum ...………………...…. 84
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N3-adamantyl-carbamoyl-1-(β-D-
ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide (32)
1H NMR spectrum ...………………………….…....…….……..…. 84
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N3-adamantyl-carbamoyl-1-(β-D-
ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide (32)
13C NMR spectrum ...…………………….………..………………. 85
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N3-adamantyl-carbamoyl-1-(β-D-
ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide (32)
IR spectrum ...…………...………….……………………..………. 85
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N3-adamantyl-carbamoyl-1-(β-D-
ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide (32)
HPLC chromatogram ...…...….…….……………………..………. 86
2’,3’,5’-Tri-O-(tert-butyldimethylsilyl)-N3-adamantyl-carbamoyl-1-(β-D-
ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide (32)
UV spectrum ...…………….…….….……………………..………. 86
N6-Adamantylcarbamoyldeoxyadenosine (33)
1H NMR spectrum ...…………….………………………………… 87
N6-Adamantylcarbamoyldeoxyadenosine (33)
13C NMR spectrum ...…………………………….………….…….. 87
N6-Adamantylcarbamoyldeoxyadenosine (33)
IR spectrum ...……………………….…………………………….. 88
N6-Adamantylcarbamoyldeoxyadenosine (33)
HPLC chromatogram ...….………….…………………………….. 88
N6-Adamantylcarbamoyldeoxyadenosine (33)
UV spectrum ...………...…………….…………………………….. 89
N6-Adamantylcarbamoyladenosine (34)
1H NMR spectrum ...……………………………………….……… 89
N6-Adamantylcarbamoyladenosine (34)
13C NMR spectrum ...……………………………….……….…….. 90
N6-Adamantylcarbamoyladenosine (34)
IR spectrum ...……….…………………………………………….. 90
N6-Adamantylcarbamoyladenosine (34)
HPLC chromatogram ...……….……….………………………….. 91
N6-Adamantylcarbamoyladenosine (34)
UV spectrum ...……….…….……..……………………………….. 91
N6-Adamantylcarbamoyl-9-β-D-arabinofuranosyladenine (35)
1H NMR spectrum ...……………………….……………………… 92
N6-Adamantylcarbamoyl-9-β-D-arabinofuranosyladenine (35)
13C NMR spectrum ...……………………………….……….…….. 92
N6-Adamantylcarbamoyl-9-β-D-arabinofuranosyladenine (35)
IR spectrum ...………………………….………………………….. 93
N6-Adamantylcarbamoyl-9-β-D-arabinofuranosyladenine (35)
HPLC chromatogram ...………………..………………………….. 93
N6-Adamantylcarbamoyl-9-β-D-arabinofuranosyladenine (35)
UV spectrum ...…………….……..…….………………………….. 94
N2-Adamantylcarbamoyldeoxyguanosine (36)
1H NMR spectrum ...………………….…………………………… 94
N2-Adamantylcarbamoyldeoxyguanosine (36)
13C NMR spectrum ...……………………….……………….…….. 95
N2-Adamantylcarbamoyldeoxyguanosine (36)
IR spectrum ...……………………….…………………………….. 95
N2-Adamantylcarbamoyldeoxyguanosine (36)
HPLC chromatogram ...………………..………………………….. 96
N2-Adamantylcarbamoyldeoxyguanosine (36)
UV spectrum ...………………..……..…………………………….. 96
N2-Adamantylcarbamoylguanosine (37)
1H NMR spectrum ...……………………………….……………… 97
N2-Adamantylcarbamoylguanosine (37)
13C NMR spectrum ...………………………………….…….…….. 97
N2-Adamantylcarbamoylguanosine (37)
IR spectrum ...…………………………….……………………….. 98
N2-Adamantylcarbamoylguanosine (37)
HPLC chromatogram ...……………..…………………………….. 98
N2-Adamantylcarbamoylguanosine (37)
UV spectrum ...…….…………..………….……………………….. 99
N2-Adamantylcarbamoyl-9-[(2-hydroxyethoxy)methyl]guanine (38)
1H NMR spectrum ...……………………….……………………… 99
N2-Adamantylcarbamoyl-9-[(2-hydroxyethoxy)methyl]guanine (38)
13C NMR spectrum ...………………………….…………….….... 100
N2-Adamantylcarbamoyl-9-[(2-hydroxyethoxy)methyl]guanine (38)
IR spectrum ...…………………….…………………………….... 100
N2-Adamantylcarbamoyl-9-[(2-hydroxyethoxy)methyl]guanine (38)
HPLC chromatogram ...…………………...…...……………...…. 101
N2-Adamantylcarbamoyl-9-[(2-hydroxyethoxy)methyl]guanine (38)
UV spectrum ...………………….…...…………………………… 101
N4-Adamantylcarbamoyldeoxycytidine (39)
1H NMR spectrum ...………………….………………………...…102
N4-Adamantylcarbamoyldeoxycytidine (39)
13C NMR spectrum ...……………………….………………...….. 102
N4-Adamantylcarbamoyldeoxycytidine (39)
IR spectrum ...……………………….………………………….... 103
N4-Adamantylcarbamoyldeoxycytidine (39)
HPLC chromatogram ...…………..……….…...……………….... 103
N4-Adamantylcarbamoyldeoxycytidine (39)
UV spectrum ...…………..…….…….………………………….... 104
N4-Adamantylcarbamoylcytidine (40)
1H NMR spectrum ...……………………………….………..…… 104
N4-Adamantylcarbamoylcytidine (40)
13C NMR spectrum ...………………………………….…...…….. 105
N4-Adamantylcarbamoylcytidine (40)
IR spectrum ...…………………………….………………..…….. 105
N4-Adamantylcarbamoylcytidine (40)
HPLC chromatogram ...………………..……………………..….. 106
N4-Adamantylcarbamoylcytidine (40)
UV spectrum ...…………………...……….………………..…….. 106
N4-Adamantylcarbamoyl-1-β-D-arabinofuranosylcytosine (41)
1H NMR spectrum ...……………………….……………..……… 107
N4-Adamantylcarbamoyl-1-β-D-arabinofuranosylcytosine (41)
13C NMR spectrum ...………………………………….…...…….. 107
N4-Adamantylcarbamoyl-1-β-D-arabinofuranosylcytosine (41)
IR spectrum ...……………………………….………………..….. 108
N4-Adamantylcarbamoyl-1-β-D-arabinofuranosylcytosine (41)
HPLC chromatogram ...…………..………....…………..……….. 108
N4-Adamantylcarbamoyl-1-β-D-arabinofuranosylcytosine (41)
UV spectrum ...…………..…….…………….………………..….. 109
N3-Adamantylcarbamoyl-1-(β-D-ribofuranosyl)-1H-1,2,4-triazole-3-
carboxamide (42) 1H NMR spectrum ...………………..….…..…. 109
N3-Adamantylcarbamoyl-1-(β-D-ribofuranosyl)-1H-1,2,4-triazole-3-
carboxamide (42) 13C NMR spectrum ...…………....……………. 110
N3-Adamantylcarbamoyl-1-(β-D-ribofuranosyl)-1H-1,2,4-triazole-3-
carboxamide (42) IR spectrum ...…………………..….…………. 110
N3-Adamantylcarbamoyl-1-(β-D-ribofuranosyl)-1H-1,2,4-triazole-3-
carboxamide (42) HPLC chromatogram ...………..……..….….... 111
N3-Adamantylcarbamoyl-1-(β-D-ribofuranosyl)-1H-1,2,4-triazole-3-
carboxamide (42) UV spectrum ...…………..……..….……..…... 111 |
參考文獻 |
1.Neyts, J.; Leyssen, P.; De Clercq, E. Molecular Strategies to Inhibit the Replication of RNA Viruses. Antiviral Res. 2008, 78, 9–25.
2.Seventh Framework Programme home page. http://cordis.europa.eu/fp7/home_en.html
3.Koonin, E. V.; Senkevich, T. G.; Dolja V. V. The Ancient Virus World and Evolution of Cells. Biol. Direct. 2006, 1, 29.
4.Sanjuan, R.; Elena, S. F. Adaptive Value of High Mutation Rates of RNA Viruses: Separating Causes from Consequences. J. Virol. 2005, 79, 11555–11558.
5.Jackwood, M. W.; Boynton, T. O.; Hilt, D. A.; McKinley, E. T.; Kissinger, J. C.; Paterson, A. H.; Robertson, J.; Lemke, C.; McCall, A. W.; Williams, S. M.; Jackwood, J. W.; Byrd, L. A. Emergence of a Group 3 Coronavirus Through Recombination. Virology. 2010, 398, 98–108.
6.Varshney, B.; Lal, S. K. SARS-CoV Accessory Protein 3b Induces AP-1 Transcriptional Activity through Activation of JNK and ERK Pathways. Biochemistry. 2011, 50, 5419–5425.
7.Zhang, H.-Z.; Zhang, H.; Kemnitzer, H.; Tseng, B.; Cinatl, J.; Jr.; Michaelis, M.; Doerr, H. W.; Cai, S. X. Design and Synthesis of Dipeptidyl Glutaminyl Fluoromethyl Ketones as Potent Severe Acute Respiratory Syndrome Coronovirus (SARS-CoV) Inhibitors. J. Med. Chem. 2006, 49, 1198–1201.
8.Cho, J. H.; Bernard, D. L.; Sidwell, R. W.; Kern, E. R.; Chu, C. K. Synthesis of Cyclopentenyl Carbocyclic Nucleosides as Potential Antiviral Agents Against Orthopoxviruses and SARS. J. Med. Chem. 2006, 49, 1140–1148.
9.Oberste, M. S.; Maher, K.; Kilpatrick, D. R.; Pallansch, M. A. Molecular Evolution of the Human Enteroviruses: Correlation of Serotype with VP1 Sequence and Application to Picornavirus Classification. J. Virol. 1999, 73, 1941–1948.
10.Ke, Y.-Y.; Lin, T.-H. Modeling the Ligand-Receptor Interaction for a Series of Inhibitors of the Capsid Protein of Enterovirus 71 Using Several Three-Dimensional Quantitative Structure-Activity Relationship Techniques. J. Med. Chem. 2006, 49, 4517–4525.
11.Arita, M.; Wakita, T.; Shimizu, H. Characterization of Pharmacologically Active Compounds that Inhibit Poliovirus and Enterovirus 71 Infectivity. J. Gen. Virol. 2008, 89, 2518–2530.0
12.Hwu, J. R.; Lin, S.-Y.; Tsay, S.-C.; Clercq, E. D.; Leyssen, P.; Neyts, J. Coumarin–Purine Ribofuranoside Conjugates as New Agents against Hepatitis C Virus. J. Med. Chem. 2011, 54, 2114–2126.
13.Whitley, R. J.; Tucker, B. C.; Kinkel, A. W.; Barton, N. H.; Pass, R. F.; Whelchel, J. D.; Cobbs, C. G.; Diethelm, A. G.; Buchanan, R. A. Pharmacology, Tolerance, and Antiviral Activity of Vidarabine Monophosphate in Humans. Antimicrob. Agents Chemother. 1980, 18, 709–715.
14.Renis, H. E. Antiviral Activity of Cytarabine in Herpesvirus- Infected Rats. Antimicrob. Agents Chemother. 1973, 4, 439–444.
15.Bacon, T. H.; Levin, M. J.; Leary, J. J.; Sarisky, R. T.; Sutton, D. Herpes Simplex Virus Resistance to Acyclovir and Penciclovir after Two Decades of Antiviral Therapy. Clin. Microbiol. Rev. 2003, 16, 114–128.
16.Crotty, S.; Cameron, C.; Andino, R. Ribavirin’s Antiviral Mechanism of Action: Lethal Mutagenesis. J. Mol. Med. 2002, 80, 86–95.
17.Balannik, V.; Wang, J.; Ohigashi, Y.; Jing, X.; Magavern, E.; Lamb, R. A.; DeGrado, W. F.; Pinto, L. H. Design and Pharmacological Characterization of Inhibitors of Amantadine-Resistant Mutants of the M2 Ion Channel of Influenza A Virus. Biochemistry. 2009, 48, 11872–11882.
18.Laohpongspaisan, C.; Rungrotmongkol, T.; Intharathep, P.; Malaisree, M.; Decha, P.; Aruksakunwong, O.; Sompornpisut, P.; Hannongbua, S. Why Amantadine Loses Its Function in Influenza M2 Mutants: MD Simulations. J. Chem. Inf. Model. 2009, 49, 847–852.
19.An, J.; Lee, C. W.; Law, H. Y.; Yang, L. H.; Poon, L. M.; Lau, S. Y.; Jones, J. M. A Novel Small-Molecule Inhibitor of the Avian Influenza H5N1 Virus Determined through Computational Screening against the Neuraminidase. J. Med. Chem. 2009, 52, 2667–2672.
20.Schiff, G. M.; Sherwood, J. R. Clinical Activity of Pleconaril in an Experimentally Induced Coxsackievirus A21 Respiratory Infection. J. Infect. Dis. 2000, 181, 20–26.
21.Wang, J.; Ma, C.; Wu, Y.; Lamb, R. A.; Pinto, L. H.; DeGrado, W. F. Exploring Organosilane Amines as Potent Inhibitors and Structural Probes of Influenza A Virus M2 Proton Channel. J. Am. Chem. Soc. 2011, 133, 13844–1384.
22.Mitsuya, H.; Weinhold, K. J.; Furman, P. A.; Clair, M.; Lehrman, S. N.; Gallo, R. C.; Bolognesi, D.; Barry, D. W.; Broder, S. 3’-Azido-3’-Deoxythymidine (BW A509U): An Antiviral Agent That Inhibits the Infectivity and Cytopathic Effect of Human T-Lymphotropic Virus Type III/Lymphadenopathy-Associated Virus in Vitro. Proc. Natl Acad. Sci. USA. 1985, 82, 7096–7100.
23.Dohnalek, J.; Hasek, J.; Duskova, J.; Petrokova, H. Hydroxyethylamine Isostere of an HIV-1 Protease Inhibitor Prefers Its Amine to the Hydroxy Group in Binding to Catalytic Aspartates. A Synchrotron Study of HIV-1 Protease in Complex with a Peptidomimetic Inhibitor. J. Med. Chem. 2002, 45, 1432-1438.
24.Gupta, S. V.; Gupta, D.; Sun, J.; Dahan, A.; Tsume, Y.; Hilfinger, J.; Lee, L.-D.; Amidon, G. L. Enhancing the Intestinal Membrane Permeability of Zanamivir: A Carrier Mediated Prodrug Approach. Mol. Pharmaceutics. 2011, 8, 2358–2367.
25.Clercq, E. D. Antiviral Drugs in Current Clinical Use. J. Clin. Virol. 2004, 30, 115– 133.
26.Yanada, R.; Obika, S.; Kobayashi, Y.; Inokuma, T.; Oyama, M.; Yanada, K.; Takemoto, Y. Stereoselective Synthesis of 3-Alkylideneoxindoles using Tandem Indium-Mediated Carbometallation and Palladium-Catalyzed Cross-Coupling Reactions. Adv. Synth. Catal. 2005, 347, 1632–1642.
27.Lebel, H.; Leogane, O. Boc-Protected Amines via a Mild and Efficient One-Pot Curtius Rearrangement. Org. Lett. 2005, 7, 4107–4110.
28.Zhu, X.-F.; Williams, H. J.; Scott, A. I. An Improved Transient Method for the Synthesis of N-Benzoylated Nucleosides. Syn. Comm. 2003, 33, 1233–1243.
29.Shelton, J. R.; Burt, S. R.; Peterson, M. A. A Broad Spectrum Anticancer Nucleoside with Selective Toxicity Against Human Colon Cells in Vitro. Bioorg. Med. Chem. Lett. 2011, 21, 1484–1487.
30.Brown, J. R.; North, E. J.; Hurdle, J. G.; Morisseau, C.; Scarborough, J. S.; Sun, D.; Kordulakova, J.; Scherman, M. S.; Jones, V.; Grzegorzewicz, A.; Crew, R. M.; Jackson, M.; McNeil, M. R.; Lee, E. E. The Structure–Activity Relationship of Urea Derivatives as Anti-Tuberculosis Agents. Bioorg. Med. Chem. 2011, 19, 5585–5595.
31.Shelton, J. R.; Cutler, C. E.; Oliveira, M.; Balzarini, J.; Peterson, M. A. Synthesis, SAR, and Preliminary Mechanistic Evaluation of Novel Antiproliferative N6,5’-Bis-ureido- and 5’-Carbamoyl-N6-ureidoadenosine Derivatives. Bioorg. Med. Chem. 2012, 20, 1008–1019.
32.Peterson, M. A.; Ke, P.; Shi. H.; Jones, C.; McDougall, B. R.; Robinson, W. E.; Jr. Design, Synthesis, and Antiviral Evaluation of Some 3’-Carboxymethyl-3’-deoxyadenosine Derivatives. Nucleosides, Nucleotides Nucleic Acids. 2007, 26, 499–519.
33.Kaloudis, P.; Paris, C.; Vrantza, D.; Encinas, S.; Perez-Ruiz, R.; Miranda, M. A.; Gimisis, T. Photolabile N-Hydroxypyrid-2(1H)-one Derivatives of Guanine Nucleosides: a New Method for Independent Guanine Radical Generation. Org. Biomol. Chem. 2009, 7, 4965–4972.
34.Park, T.; Todd, E. M.; Nakashima, S.; Zimmerman, S. C. A Quadruply Hydrogen Bonded Heterocomplex Displaying High-Fidelity Recognition. J. Am. Chem. Soc. 2005, 127, 18133–18142.
35.Wipf, P.; Li, W.; Adeyeye, C. M.; Rusnak, J. M.; Lazo, J. S. Synthesis of Chemoreversible Prodrugs of ara-C with Variable Time-Release Profiles. Biological Evaluation of Their Apoptotic Activity. Bioorgan. Med. Chem. 1996, 4, 1585–1596.
36.Douglass, J. G.; Patel, R. I.; Yerxa, B. R.; Shaver, S. R.; Watson, P. S.; Bednarski, K.; Plourde, R.; Redick, C. C.; Brubaker, K.; Jones, A. C.; Boyer, J. L. Lipophilic Modifications to Dinucleoside Polyphosphates and Nucleotides that Confer Antagonist Properties at the Platelet P2Y12 Receptor. J. Med. Chem. 2008, 51, 1007–1025.
37.Chung, D.-H.; Kumarapperuma, S. C.; Sun, Y.; Li, Q.; Chu, Y.-K.; Arterburn, J. B.; Parker, W. B.; Smith, J.; Spik, K.; Ramanathan, H. N.; Schmaljohn, C. S.; Jonsson, C. B. Synthesis of 1-β-D-Ribofuranosyl-3-ethynyl-[1,2,4]triazole and Its in Vitro and in Vivo Efficacy against Hantavirus. Antiviral Res. 2008, 79, 19–27.
38.Song, K. S.; Kim, M. J.; Seo, H. J.; Lee, S.-H.; Jung, M. E.; Kim, S.-U.; Kim, J.; Lee, J. Synthesis and Structure–Activity Relationship of Novel Diarylpyrazole Imide Analogues as CB1 Cannabinoid Receptor Ligands. Bioorg. Med. Chem. 2009, 17, 3080–3092.
39.Gerard, S.; Marchand-Brynaert, J. Protecting Group Migration in the Chemistry of 1-t-Butyldimethylsilyl-4-hydroxymethyl-2-azetidinone. Tetrahedron Lett. 2003, 44, 6339–6342.
40.Dawson, R.M.C. Data for Biochemical Research.; Oxford: Clarendon Press, 1959.
41.Pavia, D. L.; Lampman, G. M.; Kriz, G. S. Introduction to Spectroscopy.; Brooks Cole, 2008.
42.Ciuffreda, P.; Casati, S.; Manzocchi, A. Complete 1H and 13C NMR Spectral Assignment of α- and β-Adenosine, 2’-Deoxyadenosine and their Acetate Derivatives. Magn. Reson. Chem. 2007, 45, 781–784.
43.Takatsuki, K.; Ohgushi, S.; Kohmoto, S.; Kishikawa, K.; Yamamoto, M. A Simple and Efficient Synthesis of Puromycin, 2,2’-Anhydro-Pyrimidine Nucleosides, Cytidines and 2’,3’-Anhydroadenosine from 3’,5’-O-Sulfinyl Xylo-Nucleosides. Nucleosides, Nucleotides Nucleic Acids. 2006, 25, 719–734.
44.Ogilvie, K. K.; McGee, C. C.; Boisvert, S. M.; Hakimelahi, G. H.; Proba, Z. A. The Preparation of Protected Arabinonucleosides. Can. J. Chem. 1983, 61, 1204–1212.
45.Minakawa, N.; Kojima, N.; Matsuda, A. Nucleosides and Nucleotides. 184. Synthesis and Conformational Investigation of Anti-Fixed 3-Deaza-3-halopurine Ribonucleosides. J. Org. Chem. 1999, 64, 7158–7172.
46.Moriyama, K.; Suzuki, T.; Negishi, K.; Graci, J. D.; Thompson, C. N.; Cameron, C. E.; Watanabe, M. Effects of Introduction of Hydrophobic Group on Ribavirin Base on Mutation Induction and Anti-RNA Viral Activity. J. Med. Chem. 2008, 51, 159–166.
47.Patching, S. G.; Baldwin, S. A.; Baldwin, A. D.; Young, J. D.; Gallagher, M. P.; Hendersona, J. F.; Herbert, R. B. The Nucleoside Transport Proteins, NupC and NupG, from Escherichia Coli: Specific Structural Motifs Necessary for the Binding of Ligands. Org. Biomol. Chem. 2005, 3, 462–470.
48.Yan, F.; Cao, X.-X.; Jiang, H.-X.; Zhao, X.-L.; Wang, J.-Y.; Lin, Y.-H.; Liu, Q.-L.; Zhang, C.; Jiang, B.; Guo F. A Novel Water-Soluble Gossypol Derivative Increases Chemotherapeutic Sensitivity and Promotes Growth Inhibition in Colon Cancer. J. Med. Chem. 2010, 53, 5502–5510.
49.Bookser B. C.; Ugarkar B. G.; Matelich M. C.; Lemus R. H.; Allan M.; Tsuchiya M.; Nakane M.; Nagahisa A.; Wiesner J. B.; Erion M. D. Adenosine Kinase Inhibitors. 6. Synthesis, Water Solubility, and Antinociceptive Activity of 5-Phenyl-7-(5-deoxy-β-D- ribofuranosyl)pyrrolo[2,3-d]pyrimidines Substituted at C4 with Glycinamides and Related Compounds. J. Med. Chem. 2005, 48, 7808–7820.
50.Kraszni, M.; Banyai, I.; Noszal, B. Determination of Conformer-Specific Partition Coefficients in Octanol/Water Systems. J. Med. Chem. 2003, 46, 2241–2245.
51.Kerns, E. H.; Di, L. in Drug-like Properties: Concepts, Structure Design and Methods: from ADME to Toxicity Optimization.; Elsevier: NewYork, 2008.
52.Erion, M. D.; Reddy, K. R.; Boyer, S. H.; Matelich, M. C.; Gomez-Galeno, J.; Lemus, R. H.; Ugarkar, B. G.; Colby, T. J.; Schanzer, J.; van Poelje, P. D. Design, Synthesis, and Characterization of a Series of Cytochrome P450 3A-Activated Prodrugs (HepDirect Prodrugs) Useful for Targeting Phosph(on)ate-Based Drugs to the Liver. J. Am. Chem. Soc. 2004, 126, 5154–5163.
53.Qian, M.; Glaser, R. Demonstration of an Alternative Mechanism for G-to-G Cross-Link Formation. J. Am. Chem. Soc. 2005, 127, 880–887. |