Synthesis and anti-HIV-1 activity evaluation of N-1-alkyl-5-halogeno-6-alkylamino uracils as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

doi:10.5246/jcps.2011.02.018

• Full Papers • Previous Articles Next Articles

Synthesis and anti-HIV-1 activity evaluation of N-1-alkyl-5-halogeno-6-alkylamino uracils as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

Han Yan, Xiao-Wei Wang^*, Ying Guo, Zhi-Li Zhang, Jun-Yi Liu^*

1. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. State key Laboratory of Natural and Biomimetic Drug, Peking University Health Science Center, Beijing 100191 China

Received:2010-11-29 Revised:2011-02-10 Online:2011-03-15 Published:2011-03-15
Contact: Xiao-Wei Wang*, Jun-Yi Liu*

Abstract

Abstract: N-1-alkyl-5-halogeno-6-alkylamino uracils, which are novel 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio) thymine (HEPT) analogues, were synthesized as the selective and potent non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitors. Some of the compounds showed potent inhibitory activity against HIV-1 reverse transcriptase. For instance, compounds 1d, 1m and 1n exhibited potent anti-HIV-1 activity with the IC50 values of 13.3, 11.7 and 3.15 µM, respectively, which are comparable to that of nevirapine (IC50 8.38 µM).

Key words: HIV-1 reverse transcriptase, Non-nucleoside reverse transcriptase inhibitors, HEPT analogues

CLC Number:

R916

Supporting:

Han Yan, Xiao-Wei Wang^*, Ying Guo, Zhi-Li Zhang, Jun-Yi Liu^* . Synthesis and anti-HIV-1 activity evaluation of N-1-alkyl-5-halogeno-6-alkylamino uracils as novel non-nucleoside HIV-1 reverse transcriptase inhibitors [J]. , DOI: 10.5246/jcps.2011.02.018.

References

[1] Gallo, R.C.; Sarin, P.S.; Gelmann, E.P.; Robert-Guroff, M.; Richardson, E. Science. 1983, 220, 865-867.
[2] Barré-Sinoussi, F.; Chermann, J.C.; Rey, F.; Nugeyre, M.T.; Chamaret, S.; Gruest, J.; Dauguet, C.; Axler-Blin, C. Science. 1983, 220, 868-870.
[3] Essex, M.; Mclane, M.F.; Lee, T.H.; Falk, L.; Howe, C.W.S.; Mullins, J.I. Science. 1983, 220, 859-862.
[4] Gelmann, E.P.; Popovic, M.; Blayney, D.; Masur, H.; Sidhu, G.; Stahl, R.E.; Gallo, R.C. Science. 1983, 220, 862-865.
[5] Arnold, E.; Das, K.; Ding, J.; Yadav, P.N.S.; Hsiou, Y.; Boyer, P.L.; Hughes, S.H. Drug Des. Discov. 1996, 13, 29-47.
[6] Gait, M.J.; Karn, J. Trends Biotechnol. 1995, 13, 430-438.
[7] Giovanni, M.; Marco, R.; Marie-Aline, G.; Maurizio, B.; Eric, E. Viruses. 2010, 2, 880-899.
[8] Pedersen, O.S.; Pedersen, E.B. Synthesis. 2000, 4, 479-495.
[9] De Clercq, E. Chem. Biodivers. 2004, 1, 44-64.
[10] Delaugerre, C.; Rohban, R.; Simon, A. J. Med. Virol. 2001, 65, 445-448.
[11] Youcef, M.; Erik, D.C. J. Med. Chem. 2010, 53, 521-538.
[12] Tanaka, H.; Takashima, H.; Ubasawa, M.; Sekiya, K.; Nitta, I.; Baba, M.; Shigeta, S.; Walker, R.T.; De Clercq, E.; Miyasaka, T. J. Med. Chem. 1993, 35, 337-345.
[13] Andrew, L.H.; Jing, S.R.; Hiromichi, T.; Masanori, B.; Mika, O.; David, I.; Stuart, M.; David, K. J. Med. Chem. 1999, 42, 4500-4505.
[14] Debra, J.T.; George, E.W.; Neal, C.B. J. Med. Chem. 1986, 29, 676-681.
[15] Ishikawa, I.; Itoh, T.; Melik-Ohanjanian, R.G.; Takayanagi, H.; Mizuno, Y. Heterocycles. 1990, 31, 1641-1646.
[16] Murray, P.E.; McNally, V.A.; Lockyer, S.D.; Williams, K.J.; Stratford, I.J.; Jaffar, M.; Freeman, S. Bioorg. Med. Chem. 2002, 10, 525-530.
[17] Petersen, L.; Erik, B.; Nielsen, C. Synthesis. 2001, 4, 559-564.
[18] Wang, X.; Lou, Q.; Guo, Y.; Xu, Y.; Zhang, Z.; Liu, J. Org. Biomol. Chem. 2006, 4, 3252-3258.

[19] Danel, K.; Larsen, E.; Pedersen, E.B. Synthesis. 1995, 10, 934-936.

Synthesis and anti-HIV-1 activity evaluation of N-1-alkyl-5-halogeno-6-alkylamino uracils as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 6

Recommended Articles

Metrics

Comments

[1]	Yunqi Liu, Xixi Li, Xiaodong Dou, Chao Tian, Zhili Zhang, Junyi Liu, Xiaowei Wang. Similar pyridinone compounds with different activities of anti-HIV-1 reverse transcriptase [J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(7): 469-477.
[2]	Ningning Fan, Zhenming Liu, Xiaowei Wang, Junyi Liu. Docking and field-based QSAR studies of S-DABOs as HIV-1 reverse transcriptase inhibitors [J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(7): 512-520.
[3]	Xiangyi Liu, Yuanyuan Cao, Yu Zhang, Quanzhi Yang, Xiaowei Wang, Junyi Liu. Route improvement of 3-substituted-4-(2-methylcyclohexyloxy)-6-phenethylpyridinone [J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(4): 220-224.
[4]	Liang Zhang, Xiao-Wei Wang, Jun-Yi Liu^* . Synthesis and biological evaluation of novel 2-arylalkylthio-5-iodo-6-benzyl S-DABOs as potent non-nucleoside HIV-1 reverse transcriptase inhibitors [J]. , 2012, 21(1): 28-32.
[5]	Wei Wang, Li Li, Chang Liu, Liang Zhang, Han Yan, Zhi-Li Zhang, Xiao-Wei Wang, Jun-Yi Liu^*. Synthesis and biological evaluation of novel 1-aryl-5-iodo-6-benzyluracils as potent HIV-1 non-nucleoside reverse transcriptase inhibitors [J]. , 2010, 19(4): 312-317.
[6]	Xiao-Yan Ma, Zhi-Jian Cheng, Yan-Li Chen, A-Min Li, Zhi-Li Zhang, Xiao-Wei Wang, Jun-Yi Liu^* . A convenient synthesis of 1-alkyl-5-amino-6-phenylethyluracils as potential non-nucleoside HIV-1RT inhibitors [J]. , 2008, 17(4): 281-284.