New 6-benzylisocytosine derivatives were synthesized by aminolysis of 6-benzyl-2-(methylsulfanyl)pyrimidin-4(3H)-ones with aliphatic aromatic and cage-structured amines. Some of the synthesized compounds appeared to be effective HIV-1 reverse transcriptase inhibitors. Among these, 6-(2,6-difluorobenzyl)-5-methyl-2-[(2-phenylethyl)amino]pyrimidin-4(3H)-one showed the most pronounced inhibitory properties, being nine times more effective than the reference anti-HIV drug nevirapine.
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References
M. B. Navrotskii, Khim.-farm. Zh., 37(9), 22–24 (2003).
M. B. Navrotskii, Khim.-farm. Zh., 38(9), 16–18 (2004).
M. B. Navrotskii, Khim.-farm. Zh., 39(9), 16–17 (2005).
A. Mai, M. Artico, D. Rotili, et al., J. Med. Chem., 50(22), 5412–5424 (2007).
M. B. Nawrozkij, D. Rotili, D. Tarantino, et al., J. Med. Chem., 51(15), 4641–4652 (2008).
D. Rotili, D. Tarantino, M. Artico, et al., J. Med. Chem., 54(8), 3091–3096 (2011).
R. Ragno, A. Mai, G. Sbardella, et al., J. Med. Chem., 47(4), 928–934 (2004).
F. Manetti, J. A. Este, I. Clotet-Codina, et al., J. Med. Chem., 48(25), 8000–8008 (2005).
A. Mai, M. Artico, G. Sbardella, S. Massa, et al., J. Med. Chem., 38(17), 3258–3263 (1995).
A. Mai, M. Artico, G. Sbardella, S. Massa, et al., J. Med. Chem., 42(4), 619–627 (1999).
I. A. Novakov, B. S. Orlinson, M. B. Navrotskii, et al., Zh. Org. Khim., 46(11), 1684–1687 (2010).
R. Cancio, A. Mai, D. Rotili, et al., Chem. Med. Chem., 2(4), 445–448 (2007).
D. Tarantino, D. Rotili, M. B. Nawrozkij, et al., in: Abstrs. of the Nuove Prospettive in Chimica Farmaceutica (NPCF 2009): III Meeting-Workshop, Pisa (2009), Sec. 1.
G. Sbardella, A. Mai, M. Artico, et al., Med. Chem. Res., 10(1), 30–39 (2000).
L. F. Tietze and T. Eicher, Preparative Organic Chemistry [translated from Ger.], Mir, Moscow (1999).
I. A. Novakov, I. A. Kulev, S. S. Radchenko, et al., Khim.-farm. Zh., 21(4), 454–458 (1987).
A. D. Averin, E. R. Ranyuk, S. L. Golub, et al., Synthesis, 14, 2215–2221 (2007).
E. Baril, J. Mitchener, L. Lee, and B. Baril, Nucleic Acid Res., 4(8), 2641–2654 (1977).
V. O. Rechinskii, S. F. Barbashov, I. L. Dertyarev, et al., Molek. Biol., 25(5), 1248–1257 (1991).
M. Dixon, Biochem. J., 55(1), 170–171 (1953).
Acknowledgments
The present work was carried out with support from a grant from the RF President for State Support of Young Russian Scientists and Candidates of Science MK-1351.2011.3; FTP “Research and Development in Priority Directions of the Russian Science and Technology Complex for 2007 – 2012 (State Contract No. 16.512.11.2194), and the RAS Presidium Program Molecular and Cellular Biology. We thank Dr. A. V. Ten’kovtsev, Head of the Laboratory of Anisotropic and Structured Systems, RAS Institute of High-Molecular-Weight Compounds, for useful discussions during the experimental chemical part of the work and E. N. Savel’ev, Assistant in the Department of Analytical and Physical Chemistry and Polymer Physical Chemistry, Volgagrad State Technical University, for supplying the cage-structure amines.
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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 46, No. 7, pp. 11 – 14, July, 2012.
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Valuev-Elliston, V.T., Ivanov, A.V., Orlinson, B.S. et al. Synthesis and biological activity of new 6-benzylisocytosine derivatives: non-nucleoside HIV-1 reverse transcriptase inhibitors. Pharm Chem J 46, 397–401 (2012). https://doi.org/10.1007/s11094-012-0808-y
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DOI: https://doi.org/10.1007/s11094-012-0808-y