Synthesis and in vitro activity of novel N-3 acylated TSAO-T compounds against HIV-1 and HCV

European Journal of Medicinal Chemistry

Volumn 46, Issue 10, 2011, Pages 5046-5056

  Moura, Marina ^a   Josse, Solen ^a   Van Nhien, Albert Nguyen ^a   Fournier, Carole ^a,b   Duverlie, Gilles ^a,b   Castelain, Sandrine ^a,b   Soriano, Elena ^c   Marco Contelles, José ^c   Balzarini, Jan ^d   Postel, Denis ^a  

^a UNIVERSITÉ DE PICARDIE JULES VERNE   (France)

^b AMIENS UNIVERSITY HOSPITAL   (France)

^c INSTITUTO DE QUÍMICA ORGÁNICA GENERAL   (Spain)

^d REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

HCV; HIV 1; N 3 acylated nucleoside; RT inhibitor; TSAO T

Indexed keywords

[1 (2',5' BIS O TERT BUTYLDIMETHYLSILYL BETA DEXTRO RIBOFURANOSYL) 3 N (AMINOGLUTARYL)THYMINE] 3' SPIRO 5'' (4'' AMINO 1'',2'' OXATHIOLE 2'',2'' DIOXIDE); [1 (2',5' BIS O TERT BUTYLDIMETHYLSILYL BETA DEXTRO RIBOFURANOSYL) 3 N (BENZYLOXYGLUTARYL) THYMINE] 3' SPIRO 5'' (4'' AMINO 1'',2'' OXATHIOLE 2'',2''DIOXIDE); [1 (2',5' BIS O TERT BUTYLDIMETHYLSILYL BETA DEXTRO RIBOFURANOSYL) 3 N (BROMOBUTANOYL)THYMINE] 3' SPIRO 5'' (4'' AMINO 1'',2'' OXATHIOLE 2'',2'' DIOXIDE); [1 (2',5' BIS O TERT BUTYLDIMETHYLSILYL BETA DEXTRO RIBOFURANOSYL) 3 N (CYCLOPROPANOYL)THYMINE] 3' SPIRO 5'' (4'' AMINO 1'',2'' OXATHIOLE 2'',2'' DIOXIDE); [1 (2',5' BIS O TERT BUTYLDIMETHYLSILYL BETA DEXTRO RIBOFURANOSYL) 3 N (METHOXYCARBONYL)THYMINE] 3' SPIRO 5'' (4'' AMINO 1'',2'' OXATHIOLE 2'',2'' DIOXIDE); [1 (2',5' BIS O TERT BUTYLDIMETHYLSILYL BETA DEXTRO RIBOFURANOSYL) 3 N (METHOXYISOPHTALOYL) THYMINE] 3' SPIRO 5'' (4'' AMINO 1'',2'' OXATHIOLE 2'',2''DIOXIDE); [1 (2',5' BIS O TERT BUTYLDIMETHYLSILYL BETA DEXTRO RIBOFURANOSYL) 3 N (N BENZYLAMINOGLUTARYL) THYMINE] 3' SPIRO 5'' (4'' AMINO 1'',2'' OXATHIOLE 2'',2''DIOXIDE); [1 (2',5' BIS O TERT BUTYLDIMETHYLSILYL BETA DEXTRO RIBOFURANOSYL) 3 N (N METHYLAMINOGLUTARYL)THYMINE] 3' SPIRO 5'' (4'' AMINO 1'',2'' OXATHIOLE 2'',2'' DIOXIDE); [1 (2',5' BIS O TERT BUTYLDIMETHYLSILYL BETA DEXTRO RIBOFURANOSYL) 3 N (N,N DIMETHYLAMINOGLUTARYL)THYMINE] 3' SPIRO 5'' (4'' AMINO 1'',2'' OXATHIOLE 2'',2''DIOXIDE); [1 (2',5' BIS O TERT BUTYLDIMETHYLSILYL BETA DEXTRO RIBOFURANOSYL) 3 N (O METHOXYGLUTARYL)THYMINE] 3' SPIRO 5'' (4'' AMINO 1'',2'' OXATHIOLE 2'',2'' DIOXIDE); [1 (2',5' BIS O TERT BUTYLDIMETHYLSILYL BETA DEXTRO RIBOFURANOSYL) 3 N (TERT BUTOXYGLUTARYL) THYMINE] 3' SPIRO 5'' (4'' AMINO 1'',2'' OXATHIOLE 2'',2''DIOXIDE); [1 (2',5' BIS O TERT BUTYLDIMETHYLSILYL BETA DEXTRO RIBOFURANOSYL) 3 N (THIOMETHYLGLUTARYL) THYMINE] 3' SPIRO 5'' (4'' AMINO 1'',2'' OXATHIOLE 2'',2''DIOXIDE); [1 (2',5' BIS O TERT BUTYLDIMETHYLSILYL BETA DEXTRO RIBOFURANOSYL) 3 N BENZOYLTHYMINE] 3' SPIRO 5'' (4''AMINO 1'',2'' OXATHIOLE 2'',2'' DIOXIDE); ANTIVIRUS AGENT; GLUTARIC ACID; RNA DIRECTED DNA POLYMERASE INHIBITOR; THYMINE DERIVATIVE; UNCLASSIFIED DRUG;

ACYLATION; ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; CROSS COUPLING REACTION; CRYSTAL STRUCTURE; CYTOSTASIS; DRUG STRUCTURE; DRUG SYNTHESIS; HEPATITIS C VIRUS; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; IN VITRO STUDY; MOLECULAR DOCKING; NONHUMAN; NUCLEOPHILICITY; ONE POT SYNTHESIS; SUBSTITUTION REACTION; T LYMPHOCYTE; VIRUS INHIBITION;

CELL LINE; CHEMISTRY TECHNIQUES, SYNTHETIC; HEPACIVIRUS; HEPATITIS C; HIV INFECTIONS; HIV REVERSE TRANSCRIPTASE; HIV-1; HUMANS; MODELS, MOLECULAR; REVERSE TRANSCRIPTASE INHIBITORS; SMALL MOLECULE LIBRARIES; SPIRO COMPOUNDS; THYMIDINE;

EID: 80053194272     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2011.08.017     Document Type: Article

References (40)

1. M.J. Camarasa, M.J. Perez-Perez, A. San-Felix, J. Balzarini, and E. De Clercq 3′-Spiro nucleosides, a new class of specific human immunodeficiency virus type 1 inhibitors: synthesis and antiviral activity of [2′, 5′-bis-O-(tert-butyldimethylsilyl)-β-D-xylo- and -ribofuranose]-3′-spiro-5′-[4′-amino-1′, 2′-oxathiole 2′, 2′-dioxide] (TSAO) pyrimidine nucleosides J. Med. Chem. 35 1992 2721 2727
2. M.J. Perez-Perez, A. San-Felix, M.J. Camarasa, J. Balzarini, and E. De Clercq Synthesis of {1-[2′,5′-bis-O-(tert-butyldimethylsilyl)- β-D-xylo- and β-D-ribofuranosyl]thymine}-3′-spiro-5′- {4′-amino-1′,2′-oxathiole 2′,2′-dioxide} (TSAO). A novel type of specific anti-HIV agents Tetrahedron Lett. 33 1992 3029 3032
3. J. Balzarini, M.J. Perez-Perez, A. San-Felix, D. Schols, C.F. Perno, A.M. Vandamme, M.J. Camarasa, and E. De Clercq 2′,5′-Bis-O-(tert- butyldimethylsilyl)-3′-spiro-5′-(4′-amino-1′, 2′-oxathiole-2′,2′-dioxide)pyrimidine (TSAO) nucleoside analogs: highly selective inhibitors of human immunodeficiency virus type 1 that are targeted at the viral reverse transcriptase Proc. Natl. Acad. Sci. U. S. A. 89 1992 4392 4396
4. M.J. Camarasa, A. San-Felix, M.J. Perez-Perez, S. Velazquez, R. Alvarez, C. Chamorro, M.L. Jimeno, C. Perez, F. Gago, E. De Clercq, and J. Balzarini HIV-1 specific reverse transcriptase inhibitors: why are TSAO-nucleosides so unique? J. Carbohydr. Chem. 19 2000 451 469
5. M.-J. Camarasa, A. San-Felix, S. Velazquez, M.-J. Perez-Perez, F. Gago, and J. Balzarini TSAO compounds: the comprehensive story of a unique family of HIV-1 specific inhibitors of reverse transcriptase Curr. Top. Med. Chem. (Sharjah, United Arab Emirates) 4 2004 945 963 (Pubitemid 38864692)
6. J. Balzarini, A. Karlsson, M.J. Perez-Perez, M.J. Camarasa, W.G. Tarpley, and E. De Clercq Treatment of human immunodeficiency virus type 1 (HIV-1)-infected cells with combinations of HIV-1-specific inhibitors results in a different resistance pattern than does treatment with single-drug therapy J. Virol. 67 1993 5353 5359 (Pubitemid 23241368)
7. M.-C. Bonache, C. Chamorro, S. Velazquez, E. De Clercq, J. Balzarini, M.-J. Camarasa, and A. San-Felix N-3 substituted TSAO derivatives as a probe to explore the dimeric interface of HIV-1 reverse transcriptase Nucleosides, Nucleotides Nucleic Acids 22 2003 947 949 (Pubitemid 37139297)
8. M.-C. Bonache, C. Chamorro, S. Velazquez, E. De Clercq, J. Balzarini, B.F. Rodriguez, F. Gago, M.-J. Camarasa, and A. San-Felix Improving the antiviral efficacy and selectivity of HIV-1 reverse transcriptase inhibitor TSAO-T by the introduction of functional groups at the N-3 position J. Med. Chem. 48 2005 6653 6660 (Pubitemid 41509181)
9. M.-C. Bonache, E. Quesada, C.-W. Sheen, J. Balzarini, N. Sluis-Cremer, M.J. Perez-Perez, M.-J. Camarasa, and A. San-Felix Novel N-3 substituted TSAO-T derivatives: synthesis and anti-HIV-evaluation Nucleosides, Nucleotides Nucleic Acids 27 2008 351 367 (Pubitemid 351521135)
10. C. Chamorro, E. De Clercq, J. Balzarini, M.J. Camarasa, and A. San-Felix TSAO-T analogues bearing amino acids at position N-3 of thymine: synthesis and anti-human immunodeficiency virus activity Antivir. Chem. Chemother. 11 2000 61 69 (Pubitemid 30083896)
11. A. Nguyen Van Nhien, C. Tomassi, C. Len, J.L. Marco-Contelles, J. Balzarini, C. Pannecouque, E. De Clercq, D. Postel, and J. Med First synthesis and evaluation of the inhibitory effects of aza analogues of TSAO on HIV-1 replication Chem 48 2005 4276 4284 (Pubitemid 40884931)
12. C. Tomassi, A. Nguyen Van Nhien, J. Marco-Contelles, J. Balzarini, C. Pannecouque, E. De Clercq, and D. Postel Synthesis and anti-HIV1 biological activity of novel 5′-ATSAO compounds Bioorg. Med. Chem. 16 2008 4733 4741 (Pubitemid 351539016)
13. C. Tomassi, A. Nguyen Van Nhien, J. Marco-Contelles, J. Balzarini, C. Pannecouque, E. De Clercq, E. Soriano, and D. Postel Synthesis, anti-HIV-1 activity, and modeling studies of N-3 Boc TSAO compound Bioorg. Med. Chem. Lett. 18 2008 2277 2281 (Pubitemid 351442912)
14. E. Szabo, G. Lotz, C. Paska, A. Kiss, and Z. Schaff Viral hepatitis: new data on hepatitis C infection Pathol. Oncol. Res. 9 2003 215 221 (Pubitemid 38250161)
15. K.E. Sherman, S.D. Rouster, R.T. Chung, N. Rajicic, and C. Hepatitis Virus prevalence among patients infected with human immunodeficiency Virus: a cross-sectional analysis of the US adult AIDS clinical trials group Clin. Infect. Dis. 34 2002 831 837 (Pubitemid 34194855)
16. K.B. Anderson, J.L. Guest, and D. Rimland Hepatitis C virus coinfection increases mortality in HIV-infected patients in the highly active antiretroviral therapy era: data from the HIV Atlanta VA Cohort Study Clin. Infect. Dis. 39 2004 1507 1513 (Pubitemid 39518216)
17. L.K. Tsou, G.E. Dutschman, E.A. Gullen, M. Telpoukhovskaia, Y.-C. Cheng, and A.D. Hamilton Discovery of a synthetic dual inhibitor of HIV and HCV infection based on a tetrabutoxy-calix[4]arene scaffold Bioorg. Med. Chem. Lett. 20 2010 2137 2139
18. Y. Wei, C.-M. Ma, and M. Hattori Synthesis of dammarane-type triterpene derivatives and their ability to inhibit HIV and HCV proteases Bioorg. Med. Chem. 17 2009 3003 3010
19. R. De Francesco, and A. Carfi Advances in the development of new therapeutic agents targeting the NS3-4A serine protease or the NS5B RNA-dependent RNA polymerase of the hepatitis C virus Adv. Drug Deliv. Rev. 59 2007 1242 1262 (Pubitemid 350047514)
20. K. Das, J.D. Bauman, A.S. Rim, C. Dharia, A.D. Clark, M.-J. Camarasa, J. Balzarini, and E. Arnold Crystal structure of tert-Butyldimethylsilyl- spiroaminooxathioledioxide-thymine (TSAO-T) in complex with HIV-1 reverse transcriptase (RT) redefines the elastic limits of the non-nucleoside inhibitor-binding pocket J. Med. Chem. 54 2011 2727 2737
21. M. Sekine General method for the preparation of N3- and O4-substituted uridine derivatives by phase-transfer reactions J. Org. Chem. 54 1989 2321 2326 (Pubitemid 19135943)
22. J.F. Polienko, T. Schanding, Y.V. Gatilov, I.A. Grigor′ev, and M.A. Voinov Studies toward the synthesis of 4-(2-R-ethyl)amino-2,2,5,5-tetramethyl- 3-imidazoline 1-Oxyls. Nucleophilic substitution of bromide in the N-Alkyl chain of the 1,2,4-Oxadiazol-2-one precursor J. Org. Chem. 73 2008 502 510 (Pubitemid 351437408)
23. L. Bassit, J. Grier, M. Bennett, and R.F. Schinazi Combinations of 2′-C-methylcytidine analogues with interferon-α2b and triple combination with ribavirin in the hepatitis C virus replicon system Antivir. Chem. Chemother. 19 2008 25 31
24. J.-P. Sommadossi, and P. Lacolla Methods and compositions using modified nucleosides for treating flaviviruses and pestiviruses 2001 Novirio Pharmaceuticals Limited, Cayman I.; Universita Degli Studi Di Cagliari 302pp.
25. L.J. Stuyver, T. Whitaker, T.R. McBrayer, B.I. Hernandez-Santiago, S. Lostia, P.M. Tharnish, M. Ramesh, C.K. Chu, R. Jordan, J. Shi, S. Rachakonda, K.A. Watanabe, M.J. Otto, and R.F. Schinazi Ribonucleoside analogue that blocks replication of bovine viral diarrhea and hepatitis C viruses in culture Antimicrob. Agents Chemother. 47 2003 244 254 (Pubitemid 36070371)
26. J.L. Clark, L. Hollecker, J.C. Mason, L.J. Stuyver, P.M. Tharnish, S. Lostia, T.R. McBrayer, R.F. Schinazi, K.A. Watanabe, M.J. Otto, P.A. Furman, W.J. Stec, S.E. Patterson, K.W. Pankiewicz, Synthesis Design, and Antiviral Activity Of 2′-Deoxy-2′-fluoro-2′-C-methyl-cytidine, a potent inhibitor of hepatitis C virus replication J. Med. Chem. 48 2005 5504 5508 (Pubitemid 41209247)
27. A.B. Eldrup, C.R. Allerson, C.F. Bennett, S. Bera, B. Bhat, N. Bhat, M.R. Bosserman, J. Brooks, C. Burlein, S.S. Carroll, P.D. Cook, K.L. Getty, M. MacCoss, D.R. McMasters, D.B. Olsen, T.P. Prakash, M. Prhavc, Q. Song, J.E. Tomassini, and J. Xia Structure-Activity Relationship of Purine Ribonucleosides for inhibition of hepatitis C virus RNA-dependent RNA polymerase J. Med. Chem. 47 2004 2283 2295 (Pubitemid 38478852)
28. S.S. Carroll, J.E. Tomassini, M. Bosserman, K. Getty, M.W. Stahlhut, A.B. Eldrup, B. Bhat, D. Hall, A.L. Simcoe, R. LaFemina, C.A. Rutkowski, B. Wolanski, Z. Yang, G. Migliaccio, F.R. De, L.C. Kuo, M. MacCoss, and D.B. Olsen Inhibition of hepatitis C virus RNA replication by 2′-Modified nucleoside analogs J. Biol. Chem. 278 2003 11979 11984 (Pubitemid 36800172)
29. G.M. Morris, D.S. Goodsell, R. Huey, W.E. Hart, S. Halliday, R. Belew, and A.J. Olson AutoDock: Automated Docking of Flexible Ligands to Receptors, Version 3.05 2000 The Scripps Research Institute La Jolla
30. J. Ding, K. Das, C. Tantillo, W. Zhang, A.D. Clark Jr., S. Jessen, X. Lu, Y. Ysiou, and A. Jacobo-Molina a. et, Structure of HIV-1 reverse transcriptase in a complex with the non-nucleoside inhibitor α-APA R 95845 at 2.8 resolution Structure (London) 3 1995 365 379
31. M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, V.G. Zakrzewski, J.A. Montgomery Jr., R.E. Stratmann, J.C. Burant, S. Dapprich, J.M. Millam, A.D. Daniels, K.N. Kudin, M.C. Strain, O. Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski, G.A. Petersson, P.Y. Ayala, Q. Cui, K. Morokuma, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J. Cioslowski, J.V. Ortiz, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, C. Gonzalez, M. Challacombe, P.M.W. Gill, B.G. Johnson, W. Chen, M.W. Wong, J.L. Andres, M. Head-Gordon, E.S. Replogle, and J.A. Pople Gaussian98, Revision A.11.2 2001 Gaussian, Inc. Pittsburgh, PA
32. C.I. Bayly, P. Cieplak, W. Cornell, and P.A. Kollman A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: the RESP model J. Phys. Chem. 97 1993 10269 10280
33. W.L. Jorgensen, J. Chandrasekhar, J.D. Madura, R.W. Impey, and M.L. Klein Comparison of simple potential functions for simulating liquid water J. Chem. Phys. 79 1983 926 935
34. W.D. Cornell, P. Cieplak, C.I. Bayly, I.R. Gould, K.M. Merz Jr., D.M. Ferguson, D.C. Spellmeyer, T. Fox, J.W. Caldwell, and P.A. Kollman A second generation force field for the simulation of proteins, nucleic acids, and organic molecules J. Am. Chem. Soc. 117 1995 5179 5197
35. J.P. Ryckaert, G. Ciccotti, and H.J.C. Berendsen Numerical integration of the Cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes J. Comput. Phys. 23 1977 327 341
36. M.J. Perez-Perez, A. San-Felix, J. Balzarini, E. De Clercq, and M.J. Camarasa TSAO analogs. Stereospecific synthesis and anti-HIV-1 activity of 1-[2′,5′-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl] -3′-spiro-5′-(4′-amino-1′,2′-oxathiole-2′, 2′-dioxide)pyrimidine and pyrimidine-modified nucleosides J. Med. Chem. 35 1992 2988 2995
37. H. Nakabayashi, K. Taketa, K. Miyano, T. Yamane, and J. Sato Growth of human hepatoma cell lines with differentiated functions in chemically defined medium Cancer Res. 42 1982 3858 3863 (Pubitemid 12054507)
38. J.M. Vrolijk, A. Kaul, B.E. Hansen, V. Lohmann, B.L. Haagmans, S.W. Schalm, and R. Bartenschlager A replicon-based bioassay for the measurement of interferons in patients with chronic hepatitis C J. Virol. Methods 110 2003 201 209 (Pubitemid 36645265)
39. T. Wakita, T. Pietschmann, T. Kato, T. Date, M. Miyamoto, Z. Zhao, K. Murthy, A. Habermann, H.-G. Kraeusslich, M. Mizokami, R. Bartenschlager, and T.J. Liang Production of infectious hepatitis C virus in tissue culture from a cloned viral genome Nat. Med. (N. Y., NY, U. S.) 11 2005 791 796 (Pubitemid 41021213)
40. D. Delgrange, A. Pillez, S. Castelain, L. Cocquerel, Y. Rouille, J. Dubuisson, T. Wakita, G. Duverlie, and C. Wychowski Robust production of infectious viral particles in Huh-7 cells by introducing mutations in hepatitis C virus structural proteins J. Gen. Virol. 88 2007 2495 2503 (Pubitemid 47323895)