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2019 , Vol. 39 >Issue 4: 974 - 981

DOI: https://doi.org/10.6023/cjoc201808018

综述与进展

开环膦酸核苷类抗病毒药物前药的研究进展

  • 高梦远 ,
  • 刘洪涛 ,
  • 连玉菲 ,
  • 高欣丰 ,
  • 耿云鹤 ,
  • 李文燕
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  • a 河北师范大学化学与材料科学学院 石家庄 050024;
    b 河北省人民医院药学部 石家庄 050051

收稿日期: 2018-08-16

  修回日期: 2018-10-15

  网络出版日期: 2018-11-30

基金资助

河北省自然科学基金（No.H2018307055）、河北师范大学技术创新基金（No.L2017K06）资助项目.

收起

Research Progress in Prodrugs of Acyclic Nucleoside Phosphonates Antiviral Agents

  • Gao Mengyuana ,
  • Liu Hongtaob ,
  • Lian Yufeib ,
  • Gao Xinfenga ,
  • Geng Yunhea ,
  • Li Wenyan
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  • a Hebei Normal University, College of Chemistry & Material Science, Shijiazhuang 050024;
    b Department of Pharmacy, Hebei General Hospital, Shijiazhuang 050051

Received date: 2018-08-16

  Revised date: 2018-10-15

  Online published: 2018-11-30

Supported by

Project supported by the Natural Science Foundation of Hebei Province (No.H2018307055) and the Technology Innovation Foundation of Hebei Normal University (No.L2017K06).

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摘要

开环膦酸核苷类（Acyclic nucleoside phosphonates，ANPs）抗病毒药物在临床上的广泛应用使其越来越受到关注.但其结构中的游离电荷使其生物利用度较低，毒性较大，特别在治疗乙肝或艾滋病毒感染时需要长期用药，其毒性更加不可忽视.将开环膦酸核苷类抗病毒药制备成适当形式的前药，可以使其顺利吸收并在靶部位释放出原药，大幅提高生物利用度，降低毒副作用.以替诺福韦、阿德福韦和西多福韦的结构出发，综述了近几年开环膦酸核苷类前药的研究和应用近况.

关键词： 开环膦酸核苷类; 抗病毒药; 前药

本文引用格式

高梦远 , 刘洪涛 , 连玉菲 , 高欣丰 , 耿云鹤 , 李文燕 . 开环膦酸核苷类抗病毒药物前药的研究进展[J]. 有机化学, 2019 , 39(4) : 974 -981 . DOI: 10.6023/cjoc201808018

Abstract

More and more attention has been focused on acyclic nucleoside phosphonates (ANPs) antiviral agents which were wildly used in clinical therapy. However, poor oral bioavailability and high toxicity directly related to the phosphonate charge were serious and unnegligible especially for the treatment of chronic diseases such as hepatitis B virus (HBV) and human immunodeficiency virus (HIV). Preparing appropriate forms of prodrug could enhance the oral bioavailability and reduce the toxicity because of the smooth absorption of prodrugs and the release of active drug only at the target. This review summarizes some recent progress in prodrugs of ANPs antiviral agents based on the structures of tenofovir, adefovir and cidofovir.

Key words： acyclic nucleoside phosphonates (ANPs); antiviral agents; prodrug

参考文献

[1] (a) De Clercq, E. Biochem. Pharmacol. 2013, 86, 711.
(b) De Clercq, E. Adv. Pharmacol. 2013, 67, 293.
(c) De Clercq, E.; Holy, A. Nat. Rev. Drug Discovery 2005, 4, 928.
(d) Liu, K.; Xie, L. Acta Pharm. Sin. 2006, 41, 689(in Chinese).(刘琨, 谢蓝, 药学学报, 2006, 41, 689.)
[2] (a) De Clercq, E. Expert. Rev. Anti-Infect. Ther. 2003, 1, 21.
(b) De Clercq, E. Biochem. Pharmacol. 2011, 82, 99.
(c) De Clercq, E. Med. Res. Rev. 2013, 33, 1278.
[3] Peng, Y. M.; Yu, W. Q.; Li, E. T.; Kang, J. F.; Wang, Y. F.; Yang, Q. H.; Liu, B. J.; Zhang, J. M.; Li, L. Y.; Wu, J.; Jiang, J. H.; Wang, Q. D.; Chang, J. B. J. Med. Chem. 2016, 59, 3661.
[4] Pertusati, F.; Serpi, M.; McGuigan, C. Antivir. Chem. Chemother. 2012, 22, 181.
[5] De Clercq, E. Clin. Microbiol. Rev. 2003, 16, 569.
[6] De Clercq, E. Antiviral Res. 2007, 75, 1.
[7] (a) Krecmerova, M. Mini-Rev. Med. Chem. 2017, 17, 818.
(b) Hecker, S. J.; Erion, M. D. J. Med. Chem. 2008, 51, 2328.
(c) Wiemer, A. J.; Wiemer, D. F. Top. Curr. Chem. 2015, 360, 115.
(d) Xie, M. S.; Chen, Y. G.; Wu, X. X.; Qu, G. R.; Guo, H. M. Org. Lett. 2018, 20, 1212.
[8] (a) Yang, K. H.; Wang, J. T.; Li, Q. B.; Xu, W. F. Food Drug 2018, 10, 60(in Chinese).(杨康辉, 王举涛, 李乾斌, 徐文方, 食品与药品, 2018, 10, 60.)
(b) Wang, S. X.; Duan, H. D.; Meng, X.; Qin, D. W.; Wang, L. Z.; Li, X. M. J. Beijing Union Univ. (Nat. Sci.) 2010, 24, 29(in Chinese).(王世潇, 段洪东, 孟霞, 秦大伟, 王利振, 李晓萌, 北京联合大学学报(自然科学版), 2010, 24, 29.)
(c) Li, W. B.; Dong, F. H.; Sun, C. J. Prog. Pharm. Sci. 2012, 36, 300(in Chinese).(李文保, 董芳华, 孙昌俊, 药学进展, 2012, 36, 300.)
[9] Kearney, B. P.; Flaherty, J. F.; Shah, J. Clin. Pharmacokinet. 2004, 43, 595.
[10] Nelson, M. R.; Katlama, C.; Montaner, J. S.; Cooper, D. A.; Gazzard, B.; Clotet, B.; Lazzari, A.; Schewe, K.; Lange, J.; Wyatt, C. AIDS 2007, 21, 1273.
[11] Barditch-Crovo, P.; Deeks, S. G.; Collier, A.; Safrin, S.; Coakley, D. F.; Miller, M.; Kearney, B. P.; Coleman, R. L.; Lamy, P. D.; Kahn, J. O. Antimicrob. Agents Chemother. 2001, 45, 2733.
[12] Ray, A. S.; Fordyce, M. W.; Hitchcock, M. J. M. Antiviral Res. 2016, 125, 63.
[13] Ruane, P. J.; DeJesus, E.; Berger, D.; Markowitz, M.; Bredeek, U. F.; Callebaut, C.; Zhong, L.; Ramanathan, S.; Rhee, M. S.; Fordyce, M. W. J. Acquired Immune Defic. Syndr. 2013, 63, 449.
[14] (a) Sax, P. E.; Zolopa, A.; Brar, I.; Elion, R.; Ortiz, R.; Post, F.; Wang, H.; Callebaut, C.; Martin, H.; Fordyce, M. W. J. J. Acquired Immune Defic. Syndr. 2014, 67, 52.
(b) Zhang, X. Q. Acta. Pharm. Sin. 2015, 50, 509(in Chinese).(张兴权, 药学学报, 2015, 50, 509.)
[15] Painter, G. R.; Almond, M. R.; Trost, L. C.; Lampert, B. M.; Neyts, J.; De Clercq, E.; Korba, B. E.; Aldern, K. A.; Beadle, J. R.; Hostetler, K. Y. Antimicrob. Agents Chemother. 2007, 51, 3505.
[16] Lanier, E. R.; Lampert, B.; Trost, L.; Painter, G.; Almond, M. Antiviral Ther. 2008, 13, A6.
[17] Tanwandee, T.; Chatsiricharoenkul, S.; Thongsawat, S.; Sukeepaisarnjaroen, W.; Tangkijvanich, P.; Komolmit, P.; Avihingsanon, A.; Piratvisuth, T.; Sunthi, P.; Mahasanprasert, T. J. Hepatol. 2017, 66, S24.
[18] Chatsiricharoekul, S.; Jutasompakorn, P.; Niyomnaitham, S.; Matkovits, T.; Conover, M.; Cobb, J.; Greytok, J.; Sullivan-Bolyai, J. Clin. Pharmacol. Ther. 2017, 101, S48.
[19] Giesler, K. E.; Marengo, J.; Liotta, D. C. J. Med. Chem. 2016, 59, 7097.
[20] Giesler, K. E.; Liotta, D. C. J. Med. Chem. 2016, 59, 10244.
[21] Marcellin, P.; Chang, T.-T.; Lim, S. G.; Tong, M. J.; Sievert, W.; Shiffman, M. L.; Jeffers, L.; Goodman, Z.; Wulfsohn, M. S.; Xiong, S. N. Engl. J. Med. 2003, 348, 808.
[22] Marcellin, P.; Chang, T.-T.; Lim, S. G. L.; Sievert, W.; Tong, M.; Arterburn, S.; Borroto-Esoda, K.; Frederick, D.; Rousseau, F. Hepatology 2008, 48, 750.
[23] Ingiliz, P.; Valantin, M.-A.; Thibault, V.; Duvivier, C.; Dominguez, S.; Katlama, C.; Poynard, T.; Benhamou, Y. Antivir. Ther. 2008, 13, 895.
[24] Reddy, K. R.; Matelich, M. C.; Ugarkar, B. G.; Gomez-Galeno, J. E.; DaRe, J.; Ollis, K.; Sun, Z.; Craigo, W.; Colby, T. J.; Fujitaki, J. M. J. Med. Chem. 2008, 51, 666.
[25] Lin, C. C.; Fang, C.; Benetton, S.; Xu, G. F.; Yeh, U. T. Antimicrob. Agents Chemother. 2006, 50, 2926.
[26] Ding, Y.; Zhang, H.; Li, X.; Li, C.; Chen, G.; Chen, H.; Wu, M.; Niu, J. Hepatol. Int. 2017, 11, 390.
[27] Fu, X.; Jiang, S.; Li, C.; Xin, J.; Yang, Y.; Ji, R. Bioorg. Med. Chem. Lett. 2007, 17, 465.
[28] Fu, X. Z.; Wang, Y. L.; Lan, Y. Y.; Wang, A. M.; Ou, Y.; Luo, C.; Li, Y. Acta Pharm. Sin. 2010, 45, 1017(in Chinese).(傅晓钟, 王永林, 兰燕宇, 王爱民, 欧瑜, 罗春, 李燕, 药学学报, 2010, 45, 1017.)
[29] Fu, X.-Z.; Ou, Y.; Pei, J.-Y.; Liu, Y.; Li, J.; Zhou, W.; Lan, Y.-Y.; Wang, A.-M.; Wang, Y.-L. Eur. J. Med. Chem. 2012, 49, 211.
[30] Magee, W. C.; Evans, D. H. Antiviral Res. 2012, 96, 169.
[31] (a) De Clercq, E. Trends Pharmacol. Sci. 2002, 23, 456.
(b) Andrei, G.; Topalis, D.; De Schutter, T.; Snoeck, R. Antiviral Res. 2015, 114, 21.
[32] Cundy, K. C.; Bidgood, A. M.; Lynch, G.; Shaw, J. P.; Griffin, L.; Lee, W. A. Drug. Metab. Dispos. 1996, 24, 745.
[33] (a) Beadle, J. R.; Hartline, C.; Aldern, K. A.; Rodriguez, N.; Harden, E.; Kern, E. R.; Hostetler, K. Y. Antimicrob. Agents Chemother. 2002, 46, 2381.
(b) Hostetler, K. Y. Viruses 2010, 2, 2213.
[34] Marty, F. M.; Winston, D. J.; Rowley, S. D.; Vance, E.; Papanicolaou, G. A.; Mullane, K. M.; Brundage, T. M.; Robertson, A. T.; Godkin, S.; Mommeja-Marin, H. N. Engl. J. Med. 2013, 369, 1227.
[35] Marty, F. M.; Winston, D. J.; Chemaly, R. F.; Boeckh, M. J.; Mullane, K. M.; Shore, T. B.; Papanicolaou, G. A.; Morrison, M. E.; Brundage, T. M.; Mommeja-Marin, H. Biol. Blood Marrow. Transplant. 2016, 22, S23.
[36] (a) Florescu, D.; Grimley, M.; Papanicolaou, G.; Prasad, V.; Vainorius, E.; Chittick, G.; Brundage, T.; Nichols, G. Am. J. Transplant. 2018, 18, S360.
(b) Chittick, G.; Morrison, M.; Brundage, T.; Nichols, W. G. Antivir. Res. 2017, 143, 269.
[37] Dunning, J.; Kennedy, S. B.; Antierens, A.; Whitehead, J.; Ciglenecki, I.; Carson, G.; Kanapathipillai, R.; Castle, L.; Howell-Jones, R.; Pardinaz-Solis, R. PLoS One 2016, 11, e0162199.
[38] Lampertico, P. Gut 2014, 63, 869.
[39] Mak, L.-Y.; Seto, W.-K.; Lai, C.-L.; Yuen, M.-F. Expert Opin. Drug Metab. Toxicol. 2018, 14, 101.
[40] Ahn, S. H.; Kim, W.; Jung, Y. K.; Yang, J. M.; Jang, J. Y.; Kweon, Y. O.; Cho, Y. K.; Kim, Y. J.; Hong, G. Y.; Kim, D. J. J. Hepatol. 2017, 66, S88.
[41] Lai, C.-L.; Ahn, S. H.; Lee, K. S.; Um, S. H.; Cho, M.; Yoon, S. K.; Lee, J.-W.; Park, N. H.; Kweon, Y.-O.; Sohn, J. H. Gut 2014, 63, 996.
[42] Yuen, M.-F.; Ahn, S. H.; Lee, K. S.; Um, S. H.; Cho, M.; Yoon, S. K.; Lee, J.-W.; Park, N. H.; Kweon, Y. O.; Sohn, J. H. Hepatology 2013, 58, 693A.
[43] Yuen, M.-F.; Ahn, S. H.; Lee, K. S.; Um, S. H.; Cho, M.; Yoon, S. K.; Lee, J.-W.; Park, N. H.; Kweon, Y.-O.; Sohn, J. H. J. Hepatol. 2015, 62, 526.
[44] Baszczynski, O. Janeba, Z. Med. Res. Rev. 2013, 33, 1304.
[45] Luo, M.; Groaz, E.; Andrei, G.; Snoeck, R.; Kalkeri, R.; Ptak, R. G.; Hartman, T.; Buckheit, R. W., Jr.; Schols, D.; De Jonghe, S. J. Med. Chem. 2017, 60, 6220.
[46] Holy, A.; Gunter, J.; Dvorakova, H.; Masojidkova, M.; Andrei, G.; Snoeck, R.; Balzarini, J.; De Clercq, E. J. Med. Chem. 1999, 42, 2064.
[47] Jansa, P.; Baszczyňski, O.; Dracínský, M.; Votruba, I.; Zídek, Z.; Bahador, G.; Stepan, G.; Cihlar, T.; Mackman, R.; Holý, A; Jansa, Z. Eur. J. Med. Chem. 2011, 46, 3748.

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