 |
|
|
|
以作者查詢圖書館館藏 、以作者查詢臺灣博碩士 、以作者查詢全國書目 、勘誤回報 、線上人數：9 、訪客IP：3.149.235.63
姓名 徐靖汭(Ching-Jui Hsu) 查詢紙本館藏 畢業系所 化學學系 論文名稱 研究「二苯並環庚烯」及「脂芳烴」之「阿昔洛韋」共軛化合物 的結構與抗病毒活性的關係
(Study on the Structure to Antiviral Activity Relationship of Dibenzocycloheptene– and Arene–Acyclovir Conjugates)相關論文 檔案 [Endnote RIS 格式]
[相關文章]
[文章引用]
[完整記錄]
[館藏目錄]
至系統瀏覽論文 ( 永不開放)
摘要(中) 全球每年約有一千萬到一千五百萬人感染「腸病毒」(Enteroviruses)，而「腸病毒71型」(Enterovirus 71)是其中最具傳染性及致命性之病毒。台灣近二十年來爆發多次「腸病毒71型」感染，最嚴重的爆發為1998年的流行，13萬兒童得到「手足口病」、405名重症病患和78人死亡。然而對其病毒了解有限、無可使用之疫苗或專一性抗「腸病毒71型」藥物，使研發對抗「腸病毒71型」之新藥具有急迫的需要。
本實驗室以「阿昔洛韋」(Acyclovir)與「去甲替林」(Nortriptyline)做化學鍵之結合，所得分子經抗病毒測試後對「腸病毒71型」具有良好抑制的活性，但類似性質之「阿昔洛韋」與「金剛胺」(Amantadine)的共軛分子則不具有活性。據此本人改變「去甲替林」的分子結構，合成較少碳鏈之「去甲替林」、置換「脂芳烴」以增加平面性等方法，研究抗病毒活性與結構的關係，以利於未來開發出更具有抑制作用的抗「腸病毒71型」藥物。
其合成方法為將「芳烴胺」藉由「三光氣」反應成「異氰酸酯」，與含矽保護基阿昔洛韋進行加成反應，再去保護合成目標分子，並利用核磁共振光譜儀、傅立葉轉換紅外線光譜儀和高解析質譜儀鑑定其結構。摘要(英) Up to 1,500,000 individuals worldwide are infected with enteroviruses annually. Of those enteroviruses, Enterovirus71 (EV71) has spread globally, as evidenced by its highly infectious and fatal nature. A dangerous outbreak of EV71 in Taiwan over the past two decades occurred in 1998, in which nearly 130,000 children were infected with hand-foot-and-mouth disease (HFMD); 405 experienced severe neurological complications; and 78 died. Unfortunately, no effective antiviral drug treat EV71 disease. The above situation highlights the urgency of developing antienteroviral agents.
Given the above predicament, our laboratory commits itself to developing antiviral drugs, with our results demonstrating that nortriptyline–acyclovir conjugate have high replication activity, based on test results of the anti-virus "EV71." However, a similar compound, amantadine–acyclovir conjugate has no activity. Therefore, in this study, the molecular structure in which nortriptyline carbon chain length is reduced and nortriptyline is replaced by " arene " to increase the flatness of structure in order to examine the structure that describes the antiviral activity relationship.
The synthesis involved reacting arene amines with triphosgene, allowing the functional group transfer from amine to isocyanate, then reacting with acyclovir analogous by addition reaction. The target structures were examined by nuclear magnetic resonance, FT–IR spectra, and high-resolution mass spectrometry.關鍵字(中) ★ 二苯並環庚烯
★ 脂芳烴
★ 阿昔洛韋
★ 抗病毒關鍵字(英) ★ Dibenzocycloheptene
★ Arene
★ Acyclovir
★ Antiviral論文目次 目 錄
中文摘要 ............................................................................................................. i
英文摘要 ............................................................................................................ ii
謝誌 ....................................................................................................................iii
目錄 ....................................................................................................................iv
圖目錄 ................................................................................................................ x
表目錄 ............................................................................................................... xi縮寫對照表......................................................................................................... xi
一、 緒 論（Introduction）............................................................................... 1
二、 結 果（Results）....................................................................................... 7
2-1 合成含矽保護基Acyclovir–Naphthalene共軛化合物13 ...…...… 7
2-2 合成含矽保護基Acyclovir–Anthracene共軛化合物21與22 ..... 11
2-3 合成含矽保護基Acyclovir–Dibenzocycloheptene
2-4 共軛化合物27 ………...……………………………………….... 13
2-4 合成Acyclovir–Arene共軛化合物(6–9) ...……………....……... 14
三、 討 論 (Discussion) ............................................................................... 16
3-1 「Acyclovir–Naphthalene共軛化合物」的反應位置與結構 ..... 16
3-1-1 FT–IR光譜探討「Acyclovir–Naphthalene共軛化合物」
之結構……………………………...…………………...….….. 16
3-1-2 1H NMR光譜探討「Acyclovir–Naphthalene共軛化合物」
之結構 ....................................................................................... 18
3-2 形成「矽保護基Acyclovir–anthracene共軛化合物21的」
最佳化條件 ................................................................................... 19
3-3 利用UV-VIS測定「Acyclovir–Arene共軛化合物」之脂溶性 .... 20
3-4 利用UV-VIS測定「Acyclovir–Arene共軛化合物」之脂溶性 .... 22
四、 結 論（Conclusion）….......................................................................... 25
五、 實 驗 部 分（Experimental Section）….............................................. 26
N2-[(1-Naphthylmethyl)carbamoyl]-9-[(2’-hydroxyethoxy)methyl]
Guanine (6) ................................................................................... 27
N2-(9’’-Anthrcarbamoyl)-9-[(2’-hydroxyethoxy)methyl]guanine (7) ..... 28
N2-[(9’’-Anthrylmethyl)carbamoyl]-9-[(2’-hydroxyethoxy)methyl]
guanine (8) ...……..……………………………………………... 29
N2-[2-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-yliden)
ethylcarbamoyl]-9-[(2’-hydroxyethoxy)methyl]guanine (9) …..... 30
N2-(9-Anthrcarbamoyl)-9-[2’-(tert-butyldimethylsilyloxy)
ethoxymethyl]guanine (22) ...………..………….………………. 32
N2-[(9-Anthrylmethyl)carbamoyl)]-9-[2’-(tert-butyldimethylsilyloxy)
ethoxymethyl]guanine (23) ..….…………….………………...... 33
N2-[(1-Naphthylmethyl)carbamoyl]-9-[2’-(tert-butyldimethylsilyloxy)
ethoxymethyl]guanine (14) ..…………………….…….……….. 34
N2-[2-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-yliden)
ethylcarbamoyl]-9-[2’-(tert-butyldimethylsilyloxy)
ethoxymethyl]guanine (28) ...…..............................………..…… 35
六、 參 考 文 獻 （References） .................................................................. 37
七、 光 譜 ...................................................................................................... 43
1H NMR spectrum of N2-[(1-Naphthylmethyl)carbamoyl]-9-
[(2’-hydroxyethoxy)methyl]guanine (6) ...….…….…...…..……… 45
13C NMR spectrum of N2-[(1-Naphthylmethyl)carbamoyl]-9- [(2’-hydroxyethoxy)methyl]guanine (6) ....……………..….…….. 45
IR spectrum of N2-[(1-Naphthylmethyl)carbamoyl]-9- [(2’-hydroxyethoxy)methyl]guanine (6) .………..….…………….. 46
HPLC chromatogram of N2-[(1-Naphthylmethyl)carbamoyl]-9- [(2’-hydroxyethoxy)methyl]guanine (6) .………..….…………….. 46
UV spectrum of N2-[(1-Naphthylmethyl)carbamoyl]-9- [(2’-hydroxyethoxy)methyl]guanine (6) .………..….…………….. 47
1H NMR spectrum of N2-(9’’-Anthrcarbamoyl)-9-
[(2’-hydroxyethoxy)-methyl]guanine (7) ..……………….……… 47
13C NMR spectrum of N2-(9’’-Anthrcarbamoyl)-9-
[(2’-hydroxyethoxy)-methyl]guanine (7) ...……………….……… 48
IR spectrum of N2-(9’’-Anthrcarbamoyl)-9-
[(2’-hydroxyethoxy)-methyl]guanine (7) ...……………….……… 48
HPLC chromatogram of N2-(9’’-Anthrcarbamoyl)-9-
[(2’-hydroxyethoxy)-methyl]guanine (7) ..……………….……… 49
IR spectrum of N2-(9’’-Anthrcarbamoyl)-9-
[(2’-hydroxyethoxy)-methyl]guanine (7) ..……………….……… 49
1H NMR spectrum of N2-[(9’’-Anthrylmethyl)carbamoyl]-9-
[(2’-hydroxyethoxy)-methyl]guanine (8) ..……..………………… 50
13C NMR spectrum of N2-[(9’’-Anthrylmethyl)carbamoyl]-9-
[(2’-hydroxyethoxy)-methyl]guanine (8) ..……..………………… 50
IR spectrum of N2-[(9’’-Anthrylmethyl)carbamoyl]-9-
[(2’-hydroxyethoxy)-methyl]guanine (8) ..……..………………… 51
HPLC chromatogram of N2-[(9’’-Anthrylmethyl)carbamoyl]-9-
[(2’-hydroxyethoxy)-methyl]guanine (8) ..……..………………… 51
UV spectrum of N2-[(9’’-Anthrylmethyl)carbamoyl]-9-
[(2’-hydroxyethoxy)-methyl]guanine (8) ..……..………………… 52
1H NMR spectrum of N2-[2-(10,11-Dihydro-5H-dibenzo-
[a,d]cyclohepten-5-yliden)-ethylcarbamoyl]-9-
[(2’-hydroxyethoxy) methyl]guanine (9) ……………………….… 52
13C NMR spectrum of N2-[2-(10,11-Dihydro-5H-dibenzo-
[a,d]cyclohepten-5-yliden)-ethylcarbamoyl]-9-
[(2’-hydroxyethoxy) methyl]guanine (9) ……………………….… 53
IR spectrum of N2-[2-(10,11-Dihydro-5H-dibenzo-
[a,d]cyclohepten-5-yliden)-ethylcarbamoyl]-9-
[(2’-hydroxyethoxy) methyl]guanine (9) ……………………….… 53
HPLC chromatogram of N2-[2-(10,11-Dihydro-5H-dibenzo-
[a,d]cyclohepten-5-yliden)-ethylcarbamoyl]-9-
[(2’-hydroxyethoxy) methyl]guanine (9) ……………………….… 54
UV spectrum of N2-[2-(10,11-Dihydro-5H-dibenzo-
[a,d]cyclohepten-5-yliden)-ethylcarbamoyl]-9-
[(2’-hydroxyethoxy) methyl]guanine (9) ……………………….… 54
1H NMR spectrum of N2-[(1-Naphthylmethyl)carbamoyl]-9-
[2’-(tert-butyldimethylsilyloxy)ethoxymethyl]guanine (13) .…..… 55
13C NMR spectrum of N2-[(1-Naphthylmethyl)carbamoyl]-9-
[2’-(tert-butyldimethylsilyloxy)ethoxymethyl]guanine (13) .…..… 55
IR spectrum of N2-[(1-Naphthylmethyl)carbamoyl]-9-
[2’-(tert-butyldimethylsilyloxy)ethoxymethyl]guanine (13) .…..… 56
HPLC chromatogram of N2-[(1-Naphthylmethyl)carbamoyl]-9-
[2’-(tert-butyldimethylsilyloxy)ethoxymethyl]guanine (13) .…..… 56
UV spectrum of N2-[(1-Naphthylmethyl)carbamoyl]-9-
[2’-(tert-butyldimethylsilyloxy)ethoxymethyl]guanine (13) .…..… 57
1H NMR spectrum of N2-(9-Anthrcarbamoyl)-9-
[2’-(tert-butyldimethylsilyloxy)ethoxymethyl]guanine (21) ...…… 57
13C NMR spectrum of N2-(9-Anthrcarbamoyl)-9-
[2’-(tert-butyldimethylsilyloxy)ethoxymethyl]guanine (21) ..…… 58
IR spectrum of N2-(9-Anthrcarbamoyl)-9-
[2’-(tert-butyldimethylsilyloxy)ethoxymethyl]guanine (21) ..…… 58
HPLC chromatogram of N2-(9-Anthrcarbamoyl)-9-
[2’-(tert-butyldimethylsilyloxy)ethoxymethyl]guanine (21) ..…… 59
UV spectrum of N2-(9-Anthrcarbamoyl)-9-
[2’-(tert-butyldimethylsilyloxy)ethoxymethyl]guanine (21) ..…… 59
1H NMR spectrum of N2-[(9-anthrylmethyl)carbamoyl)]-9-
[2’-(tert-Butyldimethylsilyloxy)ethoxymethyl]guanine (22) …….. 60
13C NMR spectrum of N2-[(9-anthrylmethyl)carbamoyl)]-9-
[2’-(tert-Butyldimethylsilyloxy)ethoxymethyl]guanine (22) ..….... 60
IR spectrum of N2-[(9-anthrylmethyl)carbamoyl)]-9-
[2’-(tert-Butyldimethylsilyloxy)ethoxymethyl]guanine (22) ....….. 61
HPLC chromatogram of N2-[(9-anthrylmethyl)carbamoyl)]-9-
[2’-(tert-Butyldimethylsilyloxy)ethoxymethyl]guanine (22) ..….... 61
IR spectrum of N2-[(9-anthrylmethyl)carbamoyl)]-9-
[2’-(tert-Butyldimethylsilyloxy)ethoxymethyl]guanine (22) ....….. 62
1H NMR spectrum of N2-[2-(10,11-Dihydro-5H-dibenzo[a,d]-
cyclohepten-5-yliden)ethylcarbamoyl]-9-[2’-(tert-butyldimethyl-
silyloxy)ethoxymethyl]guanine (27) ...………………………….... 62
13C NMR spectrum of N2-[2-(10,11-Dihydro-5H-dibenzo[a,d]-
cyclohepten-5-yliden)ethylcarbamoyl]-9-[2’-(tert-butyldimethyl-
silyloxy)ethoxymethyl]guanine (27) ..………………………….... 63
IR spectrum of N2-[2-(10,11-Dihydro-5H-dibenzo[a,d]-
cyclohepten-5-yliden)ethylcarbamoyl]-9-[2’-(tert-butyldimethyl-
silyloxy)ethoxymethyl]guanine (27) ..………………………….... 63
HPLC chromatogram of N2-[2-(10,11-Dihydro-5H-dibenzo[a,d]-
cyclohepten-5-yliden)ethylcarbamoyl]-9-[2’-(tert-butyldimethyl-
silyloxy)ethoxymethyl]guanine (27) ..………………………….... 64
IR spectrum of N2-[2-(10,11-Dihydro-5H-dibenzo[a,d]-
cyclohepten-5-yliden)ethylcarbamoyl]-9-[2’-(tert-butyldimethyl-
silyloxy)ethoxymethyl]guanine (27) ..………………………….... 64參考文獻 1. Schmidt, N. J.; Lennette, E. H.; Ho, H. H. An apparently new enterovirus isolated from
patients with disease of the central nervous system J. Infect.Dis. 1974, 129, 304–309.
2. Wu, C.-Y.; Wang, H.-C.; Wang, K.- T.; Weng, S.-C.; Chang, W.-H.; Shih, D. Y.-C.;
Lo, C.-F.; Wang, D.-Y. Neutralization of five subgenotypes of enterovirus 71 by Taiwanese human plasma and Taiwanese plasma derived intravenous immunoglobulin.
Biologicals 2013, 41, 154–157.
3. McMinn, P. C. Recent advances in the molecular epidemiology and control of human enterovirus 71 infection. Curr. Opin. Virol. 2012, 2, 199–205.
4. McMinn PC. An overview of the evolution of enterovirus 71 and its clinical and public health significance FEMS Microbiol. Rev. 2002, 26, 91–107.
5. Huang, M.-L.; Chiang, P.-S.; Chia, M.-Y.; Luo, S.-T.; Chang, L.-Y.; Lin, T.-Y.;
Ho, M.-S.; Lee, M.-S. Cross-reactive neutralizing antibody responses to enterovirus 71 infections in young children: implications for vaccine development.
PLoS Negl. Trop. Dis. 2013, 7, e2067, 1–9.
6. Lim, X. F.; Jia, Q.; Khong, W. X.; Yan, B.; Premanand, B.; Alonso, S.; Chow, V. T. K.; Kwang, J. Characterization of an isotype-dependent monoclonal antibody against linear neutralizing epitope effective for prophylaxis of enterovirus 71 infection. PLoS ONE
2012, 7, e29751, 1-11.
7. Ho, M.; Chen, E. R.; Hsu, K. H.; Twu, S. J.; Chen, K. T.; Tsai, S. F.; Wang, J. R.; Shih, S. R. An epidemic of enterovirus 71 infection in Taiwan. New Engl. J. Med. 1999, 341, 929–935.
8. Leitch, E. C. M.; Cabrerizo, M.; Cardosa, J.; Harvala, H.; Ivanova, O. E.; Koike, S.; Kroes, A. C. M.; Lukashev, A.; Perera, D.; Roivainen, M.; Susi, P.; Trallero, G.; Evans, D. J.; Simmond, P. The association of recombination events in the founding and emergence of subgenogroup evolutionary lineages of human enterovirus 71. J. Virol. 2012, 86, 2676–2685.
9. Brown, B. A.; Pallansch, M. A. Complete nucleotide sequence of enterovirus 71 is distinct from poliovirus. Virus Res. 1995, 39, 195–205.
10. Basavappa, R.; Syed, R.; Flore, O.; Icenogle, J. P.; Filman, D. J.; Hogle, J. M. Role and mechanism of the maturation cleavage of VPO in poliovirus assembly: Structure of the empty capsid assembly intermediate at 2.9 Å resolution. Protein Sci.1994, 3, 1651–1669.
11. Blair, W. S.; Hwang, S. S.; Y.-W., M. F. ; Semler, B. L. A mutant poliovirus containing a novel proteolytic cleavage site in VP3 is altered in viral maturation. J. Virol. 1990, 64, 1784–1793.
12. Larsen, G. R.; Anderson, C. W.; Dorner, A. J.; Semler, B. L.; Wimmer, E. Cleavage sites within the poliovirus capsid protein precursors. J. Virol.1982, 41, 340–344.
13. Nagata, N.; Shimizu, H.; Ami, Y.; Tano, Y.; Harashima, A.; Suzaki, Y.; Sato, Y.; Miyamura, T.; Sata, T.; Iwasaki, T. Pyramidal and extrapyramidal involvement in experimental infection of cynomolgus monkeys with enterovirus 71. J. Med. Virol. 2002, 67, 207–216.
14. Nagata, N.; Iwasaki, T.; Ami, Y. ; Tano, Y.; Harashima, A. ; Suzaki, Y.; Sato, Y.; Hasegawa, H.; Sata, T.; Miyamura, T.; Shimizu, H. Differential localization of neurons susceptible to enterovirus 71 and poliovirus type 1 in the central nervous system of cynomolgus monkeys after intravenous inoculation. J. Gen. Virol. 2004, 85, 2981–2989.
15. Chang, L. Y.; Lin, T. Y.; Hsu, K. H.; Huang, Y. C.; Lin, K. L.; Hsueh, C.; Shih, S. R.;Ning, H. C.; Hwang, M. S.; Wang, H. S.; Lee, C. Y. Clinical features and risk factors of pulmonary oedema after enterovirus-71-related hand, foot , and mouth disease. Lancet 1999, 354, 1682–1686.
16. Bible, J. M.; Pantelidis, P.; Chan, P. K.; Tong, C. Y. Genetic evolution of enterovirus 71: epidemiological and pathological implications. Rev. Med. Virol. 2007, 17, 371–379.
17. Wang, S.-M.; Ho, T.-S.; Lin, H.-C.; Lei, H.-Y.; Wang, J.-R.; Liu, C.-C. Reemerging of enterovirus 71 in Taiwan: the age impact on disease severity. Eur. J. Clin. Microbiol. Infect. Dis. 2012, 31, 1219–1224.
18. Chang, L. Y.; Huang, L. M.; Gau, S. S.; Wu, Y. Y.; Hsia, S. H.; Fan, T. Y.; Lin, K. L.; Huang, Y. C.; Lu, C. Y.; Lin, T. Y. Neurodevelopment and cognition in children after enterovirus 71 infection. Lancet 2007, 356, 1226–1234.
19. Gau, S. S.; Chang, L. M.; Fan, T. Y.;Wu, Y. Y.; Lin, T. Y. Attention-deficit/hyperactivity–related symptoms among children with enterovirus 71 infection of the central nervous system. Pediatrics 2008, 122, 452–458.
20. Seventh Framework Programme home page. http://cordis.europa.eu/fp7/home_en.html
21. 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.
22. 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.
23. 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.
24. Arita, M.; Takebe, Y.; Wakita1, T.; Shimizu1, H. A bifunctional anti-enterovirus compound that inhibits replication and the early stage of enterovirus 71 infection.
J. Gen. Virol. 2010, 91, 2734–2744.
25. Glaser, R.; Qian, M. Demonstration of an alternative mechanism for G-to-G cross-link formation. J. Am. Chem. Soc. 2005, 127, 880–887.
26. Charalambides, Y. C.; Moratti, S. C. Comparison of base-promoted and self-catalyzed conditions in the synthesis of isocyanates from amines using triphosgene.
Synthetic Commun. 2007, 37, 1037–1044.
27. Franks, W. R.; Creec, H. J. Anthranyl and 1,2,5,6-Dibenzanthranyl Isocyanates. I
J. Am. Chem. Soc, 1938, 60, 127–128.
28. Xu, W.; Su, L.; Cao, J.; Jia, Y.; Zhang, X.; Fang, H. Development of synthetic aminopeptidase N/CD13 inhibitors to overcome cancer metastasis and angiogenesis. ACS Med. Chem. Lett. 2012, 3, 959–964.
29. Boudou, V.; Langridge, J.; van Aerschot, A. Synthesis of the Anticodon Hairpin tRNAfMet Containing N-{[9-(b-d-Ribofuranosyl)-9H-purin-6-yl]carbamoyl}-l-threonine (=N6-{{[(1S,2R)-1-Carboxy-2-hydroxypropyl]amino}carbonyl}adenosine, t6A)
Helv. Chim. Acta 2000, 83, 152–161.
30. Adams, H.; Bawa, R. A.; McMillan, K. G.; Jones, S. Asymmetric control in Diels–Alder cycloadditions of chiral 9-aminoanthracenes by relay of stereochemical information. Tetrahedron : Asymmetry 2007, 18, 1003–1012.
31. Horiguchi, M.; Ito, Y. Solvent-dependent effect by carbon dioxide on the photoreactions of (9-anthryl)alkylamines. Tetrahedron 2007, 63, 12286–12293.
32. 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.
33. Bent, A.; Blommaert, A. G. S.; Melman, C. T. M.; IJzerman, A. P.; Wijngaarden, I.; Soudijn, W. Hybrid cholecystokinin-A antagonists based on molecular modeling of lorglumide and L-364,718. J. Med. Chem. 1992, 35, 1042–1049.
34. Gerard, S.; M.-B., J. Protecting group migration in the chemistry of 1-t-butyldimethylsilyl-4-hydroxymethyl-2-azetidinone. Tetrahedron Lett. 2003, 44, 6339–6342.
35. Reddy, A. S.; Sastry, G. N. Cation [M = H+, Li+, Na+, K+, Ca2+, Mg2+, NH4+, and NMe4+] interactions with the aromatic motifs of naturally occurring amino acids: A theoretical study. J. Phys. Chem. 2005, 109, 8893–8903.
36. Jennifer, C. M.; Dennis, A. D. The Cation-π Interaction. Chem. Rev. 1997, 97, 1303–1324.
37. Peter, K. B.; Wojciech, T. M.; Colin, B. R. Acylation of 2’,3’,5’ -Tri-Q –acetylguanosine. J.C.S. Chem. Commun. 1977, 791–792.
38. Pavia, D. L.; Lampman, G. M.; Kriz, G. S. in Introduction to spectroscopy, 4nd ed.; Brooks Cole, 2008.
39. Ten, C. A. T.; Dankers, P. Y. W.; Kooijman, H.; Spek, A. L.; Sijbesma, R. P.; Meijer, E.W. enantioselective cyclization of racemic supramolecular polymers.
J. Am. Chem. Soc. 2003, 125, 6860–6861.
40. 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.
41. Dawson, R. M. C. in Data for Biochemical Research, 3nd ed.; Oxford, Clarendon Press, 2002.
42. Paquette L. A. in Encyclopedia of reagents for organic synthesis, 1nd ed.; John Wiley & Sons, cop., 1995
43. Smith, D. A.; Beaumont, K.; Walker, D. K.; van de Waterbeemd, H. Property-based design: Optimization of drug absorption and pharmacokinetics. J. Med. Chem. 2001, 44, 1313–1333.
44. Ishikawa, M.; Hashimoto, Y. Improvement in aqueous solubility in small molecule drug discoveryprograms by disruption of molecular planarity and symmetry. J. Med. Chem. 2011, 54, 1539–1554.
45. 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.
46. Kraszni, M.; Banyai, I.; Noszal, B. Determination of conformer-specific partition coefficients in octanol/water systems. J. Med. Chem. 2003, 46, 2241–2245.
47. Kerns, E. H.; Di, L. in Drug-like Properties: Concepts, Structure Design and Methods: from ADME to Toxicity Optimization, 1nd ed.; Elsevier: NewYork, 2008.指導教授 胡紀如(Jih-Ru Hwu) 審核日期 2013-8-12 推文 plurk
funp
live
udn
HD
myshare
netvibes
friend
youpush
delicious
baidu
網路書籤 Google bookmarks
del.icio.us
hemidemi
facebook
twitter
google
reddit