Novel L-lyxo and 5'-deoxy-5'-modified TSAO-T analogs: Synthesis and anti-HIV-1 activity

Antiviral Research

Volumn 32, Issue 3, 1996, Pages 149-164

  Ingate, Simon ^a   De Clercq, Erik ^b   Balzarini, Jan ^b   Camarasa, María José ^a  

^a INSTITUTO DE QUÍMICA MÉDICA   (Spain)

^b REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

3' Spironucleoside; 5' Deoxy 5' modified TSAO T; AIDS; HIV; HIV 1 specific reverse transcriptase inhibitor; L lyxo TSAO T; Reverse transcriptase inhibitor; TSAO T

Indexed keywords

NUCLEOSIDE DERIVATIVE; RNA DIRECTED DNA POLYMERASE INHIBITOR; THYMINE DERIVATIVE;

ANTIVIRAL ACTIVITY; ARTICLE; CELL CULTURE; CHIRALITY; CONTROLLED STUDY; CYTOTOXICITY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 2; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; REACTION ANALYSIS; STEREOCHEMISTRY;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 2;

EID: 0030297958     PISSN: 01663542     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0166-3542(95)00989-2     Document Type: Article

References (45)

1. Alvarez, R., Velázquez, S., San-Félix, A., Aquaro, S., De Clercq, E., Perno, C.F., Karlsson, A., Balzarini, J. and Camarasa, M.J. (1994) 1,2,3-Triazole-[2′,5′-bis-O-tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3′-spiro-5″-(4″-amino-1″,2″-oxathiole-2″,2″-dioxide) (TSAO) analogues: synthesis and anti-HIV-1 activity. J. Med. Chem. 37, 4185-4194.
2. Baba, M., Tanaka, H., De Clercq, E., Pauwels, R., Balzarini, J., Schols, D., Nakashima, H., Perno, C.F., Walker, R.T. and Miyasaka, T. (1989) Highly specific inhibition of human immunodeficiency virus type 1 by a novel 6-substituted acyclouridine derivative. Biochem. Biophys. Res. Commun. 165, 1375-1381.
3. Balzarini, J., Pérez-Pérez, M.J., San-Félix, A., Camarasa, M.J., Bathurst, I.C., Barr, P.J. and De Clercq, E. (1992a) Kinetics of inhibition of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase by the novel HIV-1 specific nucleoside analogue 2′,5′-bis-O-(tert-butyldimethylsilyl)-3′-spiro-5″-(4″-amino-1″,2″-oxathiole-2″,2″-dioxide)thymine (TSAO-T). J. Biol. Chem. 267, 11831-11838.
4. Balzarini, J., Pérez-Pérez, M.J., San-Félix, A., Schols, D., Perno, C.F., Vandamme, A.M., Camarasa, M.J. and De Clercq, E. (1992b) 2′,5′-Bis-O-(tert-butyldimethylsilyl)-3′-spiro-5″-(4″-amino-1″,2″-oxathiole-2″,2″-dioxide) pyrimidine (TSAO) nucleoside analogues: highly selective inhibitors of human immunodeficiency virus type 1 that are targeted at the viral reverse transcriptase. Proc. Natl. Acad. Sci. USA 89, 4392-4396.
5. Balzarini, J., Pérez-Pérez, M.J., San-Félix, A., Velázquez, S., Camarasa, M.J. and De Clercq, E. (1992c) [2′,5′-Bis-O-(tert-butyldimethylsilyl)-3′-spiro-5″-[4″-amino-1″,2″-oxathiole-2″,2″-dioxide] (TSAO) derivatives of purine and pyrimidine nucleosides as potent selective inhibitors of human immunodeficiency virus type 1. Antimicrob. Agents Chemother. 36, 1073-1080.
6. Balzarini, J., Camarasa, M.J. and Karlsson, A. (1993a) TSAO derivatives: highly specific human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitors. Drugs Future 18, 1043-1055.
7. Balzarini, J., Karlsson, A., Pérez-Pérez. M.J., Vrang, L., Öberg, B., Vandamme, A.M., Camarasa, M.J. and De Clercq, E. (1993b) Differential sensitivity of HIV-1 mutant strains to HIV-1 specific RT inhibitors depending on the aminoacid substitution in the mutated reverse transcriptase (RT). Virology 192, 246-253.
8. Balzarini, J., Karlsson, A., Vandamme A.M., Pérez-Pérez, M.J., Zhang H., Vrang, E., Öberg. B., Bäckbro, K., Unge, T., San-Félix, A., Velázquez S., Camarasa, M.J. and De Clercq, E. (1993c) Human immunodeficiency virus type 1 (HIV-1) strains selected for resistance against the HIV-1-specific [2′,5′-bis-O-(tert/-butyldimethylsilyl)-3′-spiro-5″-(4″-amino-1″,2″-oxathiole-2″,2″-dioxide)-β-D-pentofuranosyl (TSAO) nucleoside analogues retain sensitivity to HIV-1-specific non-nucleoside inhibitors. Proc. Natl. Acad. Sci. USA 90, 6952-6956.
9. 3T). Biochem. Pharmacol. 46, 69-77.
10. Balzarini, J., Kleim, J.-P., Riess, G., Camarasa, M.J., De Clercq, E. and Karlsson, A. (1994) Sensitivity of (138-Glu → Lys) mutated human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) to HIV-1-specific RT inhibitors. Biochem. Biophys. Res. Commun. 201, 1305-1312.
11. Bourgeois, J.M. (1974) Synthèse de sucres aminés ramifiés II. Synthèse et réactions de spiro-aziridines. Helv. Chim. Acta 57, 2553-2557.
12. Boyer P.L., Ding, J., Arnold E. and Hughes S.H. (1994) Subunit specificity of mutations that confer resistance to non-nucleoside inhibitors in human immunodeficiency-virus type 1 reverse transcriptase. Antimicrob. Agents Chemother. 38, 1909-1914.
13. Calvo-Mateo, A., Camarasa, M.J., Díaz-Ortíz, A., and de las Heras, F.G. (1988) Novel aldol-type cyclocondensation of O-mesyl (methylsulphonyl)cyanohydrins. Application to the stereo specific synthesis of branched-chain sugars. J. Chem. Soc., Chem. Commun, 1114-1115.
14. Camarasa, M.J., Pérez-Pérez, M.J., San-Félix, A., Balzarini, J. and De Clercq, E. (1992) 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 β-D-ribofuranose] -3′-spiro-5″-[4″-amino-1″,2″-oxathiole-2″,2″-dioxide] (TSAO) pyrimidine nucleosides. J. Med. Chem. 35, 2721-2727.
15. Camarasa, MJ., Pérez-Pérez, M.J., Velázquez, S., San-Félix, A., Alvarez, R., Ingate, S., Jimeno, M.L., Karlsson, A., De Clercq, E. and Balzarini, J. (1995) TSAO derivatives: highly specific inhibitors of human immunodeficiency virus type-1 (HIV-1) replication. Nucleosides Nucleotides 14, 585-594.
16. Génu-Dellac, C., Gosselin, G. and Imbach, J.L. (1991) Preparation of new acylated derivatives of L-arabinofuranose and 2-deoxy-L-erythro-pentofuranose as precursors for the synthesis of L-pentofuranosyl nucleosides. Carbohydr. Res. 216, 249-255.
17. Goldman, M.E., Nunberg, J.H., O'Brien, J.A., Quintero, J.C., Schleif, W.A., Freund, K.F., Gaul, S.L., Saari, W.S., Wai, J.S., Hoffman, J.M., Anderson, P.S., Hupe, D.J., Emini, E.A. and Stern, A.M. (1991) Pyridinone derivatives: specific human immunodeficiency virus type 1 reverse transcriptase inhibitors with antiviral activity. Proc. Natl. Acad. Sci. USA 88, 6863-6867.
18. Hildebrandt, B., Nakamura, Y. and Ogawa, S. (1991) Practical synthesis of optically pure 3,4-epoxy-5-methyldihydro-2(3H)-furanones from D-xylose by regio-and stereo-selective functionalisation. Carbohydr. Res. 214, 87-93.
19. Hollemberg, D.H., Klein R.S. and Fox. J.J. (1978) Pyridinium dichromate for the oxidation of carbohydrates. Carbohydr. Res. 67, 491-494.
20. Ingate, S., Camarasa, M.J., De Clercq, E. and Balzarini, J. (1995a) Synthesis and anti-HIV-1 activity of [1-[2′,5′-Bis-O-(tert-butyldimethylsilyl)-β-L-ribofuranosyl]thymine]-3′-spiro-5″-(4″-amino-1″,2″-oxathiole-2″,2″-dioxide) (L-TSAO), the L-enantiomer of the highly specific HIV-1 reverse transcriptase inhibitor TSAO-T. Antiviral Chem. Chemother. 6, 365-370.
21. Ingate, S., Pérez-Pérez, M.J., De Clercq, E., Balzarini, J. and Camarasa, M.J. (1995b) Synthesis and anti-HIV-1 activity of novel TSAO-T derivatives modified at the 2′-and 5′-positions of the sugar moiety. Antiviral Res. 27, 281-299.
22. Ingate, S., San-Félix, A., De Clercq, E., Balzarini, J. and Camarasa, M.J. (1995c) Synthesis of [1-[2′,5′-bis-O-(t-butyldimethylsilyl)-β-L-ribofuranosyl]thymine]-3′-spiro-5″-(4″-amino-1″,2″-oxathiole-2″,2″-dioxide) (L-TSAO-T). Nucleosides Nucleotides. 14, 299-301.
23. Jonckheere, H., Taymans, J.M., Balzarini, J., Velázquez, S., Camarasa, M.J., Desmyter, J., De Clercq, E. and Anné, J. (1994) Resistance of HIV-1 reverse transcriptase (RT) against TSAO derivatives is determined by the mutation 138Glu → Lys on the p51 subunit. J. Biol. Chem. 269, 25255-25258.
24. Kleim, J.P., Bender, R., Billhardt, U.M., Meichsner, C., Rieb, G., Rosner, M., Winkler, I. and Paessens, A. (1993) Activity of a novel quinoxaline derivative against human immunodeficiency virus type 1 reverse transcriptase and viral replication. Antimicrob. Agents Chemother. 37, 1659-1664.
25. Koup, R.A., Merluzzi, V.J., Hargrave, K.D., Adams, J., Grozinger, K., Eckner, R.J. and Sullivan, J.L. (1991) Inhibition of human immunodeficiency virus type 1 (HIV-1) replication by the dipyridodiazepinone BI-RG-587. J. Infect. Dis. 163, 966-970.
26. Levene, P.A. and Raymond, A.L. (1933) Derivatives of monoacetone xylose. J. Biol. Chem. 102, 317-330.
27. Merluzzi, V.J., Hargrave, K.D., Labadia, M., Grozinger, K., Skoog, M., Wu, J.C., Shih, C.K., Eckner, K., Hattox, S., Adams. J., Rosenthal, A.S., Faanes, R., Eckner, R.J., Koup, R.A. and Sullivan, J.L. (1990) Inhibition of HIV-I replication by a nonnucleoside reverse transcriptase inhibitor. Science 250, 1411-1413.
28. Miyasaka, T., Tanaka, H., Baba, M., Hayakawa, H., Walker, R.T., Balzarini, J. and De Clercq, E. (1989) A novel lead for specific anti-HIV-1 agents: 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine. J. Med. Chem. 32, 2507-2509.
29. Pauwels, R., Andries, K., Desmyter, J., Schols, D., Kukla, M.J., Breslin, H.J., Raeymaeckers, A., Van Gelder, J., Woestenborghs, R., Heykants, J., Schellekens, K., Janssen, M.A.C., De Clercq, E. and Janssen, P.A.J. (1990) Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives. Nature 343, 470-474.
30. Pauwels, R., Andries, K., Debyser, Z., Van Daele, P., Schols, D., Stoffels, P., De Vreese, K., Woestenborghs, R., Vandamme, A.-M., Janssen, M.G.C., Anné, J., Cauwenbergh, G., Desmyter, J., Heykants. J., Janssen, M.A.C., De Clercq, E. and Janssen, P.A.J. (1993) Potent and highly selective HIV-1 inhibition by a new series of x-anilino phenyl acetamide (x-APA) derivatives targeted at HIV-1 reverse transcriptase. Proc. Natl. Acad. Sci. USA 90, 1711-1715.
31. Pérez-Pérez, M.J., Camarasa, M.J., Diaz-Ortiz, A., San Félix, A. and de las Heras, E.G. (1991) Stereospecific synthesis of branched-chain sugars by a novel aldol-type cyclocondensation. Carbohydr. Res. 216, 399-411.
32. Pérez-Pérez, M.J., San-Félix, A., Balzarini, J., De Clercq, E. and Camarasa, M.J. (1992) TSAO analogues. Stereospecific synthesis and anti-HIV-1 activity of 1-[2́,5́-Bis-O-(tert-butyldimetylsilyl)-β-D-ribofuranosyl]-3′-spiro-5″-(4″-amino-1″,2″-oxathiole-2″,2″-dioxide) pyrimidine and pyrimidine modified nucleosides. J. Med. Chem. 35, 2988-2995.
33. Pougny, J.-R. and Sinay, P. (1978) Synthesis of (+) and (-) tetrahydrocerulenin from D-xylose revised stereochemistry of natural (+) cerulenin. Tetrahedron Lett. 35, 3301-3304.
34. Ren, J., Esnouf, R., Carman, E., Somers, D., Ross, C., Kirby, I., Keeling, J., Darby, G., Jones, Y., Stuart. D. and Stammers, D. (1995) High resolution structures of HIV-1 RT from four RT-inhibitor complexes. Nature Struct. Biol. 2(4), 293-302.
35. Romero, D.L., Busso, M., Tan, C.K., Reusser, F., Palmer, J.R., Poppe, S.M., Aristoff, P.A., Downey, K.M., So, A.C., Resnick, L. and Tarpley, W.G. (1991) Nonnucleoside reverse transcriptase inhibitors that potently and specifically block human immunodeficiency virus type-1 replication. Proc. Natl. Acad. Sci. USA 88, 8806-8810.
36. Romero, D.L., Morge, R.A., Biles, C., Berrios-Peña, N., May, P.D., Palmer, J.R., Johnson, P.D., Smith, H.W., Busso, M., Tan, C.-K., Voorman, R.L., Reusser, F., Althaus, I.W., Downey. K.M., So, A.G., Resnick, L., Tarpley, W.G. and Aristoff, P.A. (1994) Discovery, synthesis, and bioactivity of bis(heteroaryl)piperazines 1. A novel class of non-nucleoside HIV-1 reverse transcriptase inhibitors. J. Med. Chem. 37, 337-345.
37. San-Félix, A., Velázquez, S., Pérez-Pérez, M.J., Balzarini, J., De Clercq, E. and Camarasa, M.J. (1994) Novel series of TSAO-T derivatives. Synthesis and anti-HIV-1 activity of 4-, 5-, and 6-substituted pyrimidine analogues. J. Med. Chem. 37, 453-460.
38. Smerdon, S.J., Jäger, J., Wang, J., Kohlstaedt, L.A., Chirino, A.J., Freidma, J.M.. Rice, P.A. and Steitz, T.A. (1994) Structure of the binding site for nonnucleoside inhibitors of the reverse transcriptase of human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. USA 91, 3911-3915.
39. Tantillo, C., Ding, J., Jacobo-Molina, A., Nanni, R.G., Boyer, P.L., Hughes, S.H., Pauwels, R., Andries, K., Janssen, P.A.J. and Arnold, E. (1994) Locations of anti-AIDS drug binding sites and resistance mutations in the three-dimensional structure of HIV-1 reverse transcriptase. J. Mol. Biol. 243, 369-387.
40. Thang, T.T., Winternitz, F., Lagrange, A., Oleste, A. and Lukas, G. (1980) Stereospecific access to branched-chain carbohydrate synthons. Tetrahedron Lett. 21, 4495-4498.
41. Tatsuta, K., Amemiya, Y., Kanemura, Y. and Kinoshita, M. (1981) Total synthesis of tylonolide, an aglycone of tylosin. Tetrahedron Lett. 40, 3997-4000.
42. Velázquez, S., San-Félix, A., Pérez-Pérez, M.J., Balzarini, J., De Clercq. E. and Camarasa, M.J. (1993) TSAO analogues 3. Synthesis and anti-HIV-1 activity of 2′,5′-bis-O-(tert-butyldimetylsilyl)-β-D-ribofuranosyl]-3′-spiro-5″-(4″-amino -1″,2″-oxathiole-2″,2″-dioxide) purine and purine-modified nucleosides. J. Med. Chem. 36, 3230-3239.
43. Velázquez, S., Jimeneo, M.L. and Camarasa, M.J. (1994) Synthesis of [1-[3́,5́-bis-O-(tert-butyldimethylsilyl)-β-D-arabino-and β-D-ribofuranosyl]cytosine]-2′-spiro-5″-(4″-amino-1″,2″-oxathiole-2″,2″-dioxide). Analogues of the highly specific anti-HIV-1 agent TSAO-T. Tetrahedron 37, 11013-11022.
44. Vorbrüggen, H., Krolikiewicz, K. and Bennua, B. (1981) Nucleoside synthesis with trimethylsilyl triflate and as catalysts. Chem. Ber. 114, 1234-1256.
45. Yoshimura, J., Aqeel, A., Hong, N., Sato, K. and Hashimoto, H. (1986) Syntheses of D-rubranitrose and methyl x-D-tetrorithose by cyanomesylation of hexopyranosid-3-uloses. Carbohydr. Res. 155, 236-246.