1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazine (TTD) derivatives: A new class of nonnucleoside human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitors with anti-HIV-1 activity

Antimicrobial Agents and Chemotherapy

Volumn 42, Issue 3, 1998, Pages 618-623

  Witvrouw, M ^a   Arranz, M E ^b   Pannecouque, C ^a   Declercq, R ^c   Jonckheere, H ^a   Schmit, J C ^a   Vandamme, A M ^a   Diaz, J A ^b   Ingate, S T ^b   Desmyter, J ^a   Esnouf, R ^a   Van Meervelt, L ^c   Vega, S ^b   Balzarini, J ^a   De Clercq, E ^a  

^a REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^b INSTITUTO DE QUÍMICA MÉDICA   (Spain)

^c UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

2 (3 FLUOROBENZYL) 4 CYANOMETHYLENE 1,1,3 TRIOXO 2H,4H THIENO[3,4 E][1,2,4]THIADIAZINE; 2 BENZYL 4 CYANOMETHYLENE 1,1,3 TRIOXO 2H,4H THIENO[3,4 E][1,2,4]THIADIAZINE; 3 [(4,7 DICHLORO 2 BENZOXAZOLYLMETHYL)AMINO] 5 ETHYL 6 METHYL 2(1H) PYRIDONE; 3 [2 (2 BENZOXAZOLYL)ETHYL] 5 ETHYL 6 METHYL 2(1H) PYRIDONE; DELAVIRDINE; DIDANOSINE; LAMIVUDINE; LOVIRIDE; NEVIRAPINE; RNA DIRECTED DNA POLYMERASE INHIBITOR; THIADIAZINE DERIVATIVE; TIVIRAPINE; UNCLASSIFIED DRUG; ZIDOVUDINE;

ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; CROSS RESISTANCE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 2; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; PRIORITY JOURNAL; SIMIAN IMMUNODEFICIENCY VIRUS; VIRUS REPLICATION; VIRUS RESISTANCE; VIRUS STRAIN;

EID: 0031938084     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/aac.42.3.618     Document Type: Article

References (52)

1. Ahgren, C., K. Backro, F. W. Bell, A. S. Cantrell, M. Clemens, J. M. Colacino, J. B. Deeter, J. A. Engelhardt, M. Hogberg, S. R. Jaskunas, N. G. Johansson, C. L. Jordan, J. S. Kasher, M. D. Kinnick, P. Lind, C. Lopez, J. M. Morin, M. A. Muesing, R. Noreen, B. Oberg, C. J. Paget, J. A. Palkowitz, C. A. Parrish, P. Pranc, M. K. Rippy, C. Rydergard, C. Sahlberg, S. Swanson, R. J. Ternansky, T. Unge, R. T. Vasileff, L. Vrang, S. J. West, H. Zhang, and X.-X. Zhou. 1995. The PETT series, a new class of potent nonnucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. Antimicrob. Agents Chemother. 39:1329-1335.
2. Baba, M., M. Ito, S. Shigeta, and E. De Clercq. 1984. Synergistic antiviral effects of antiherpes compounds and human leukocyte interferon on varicella-zoster virus in vitro. Antimicrob. Agents Chemother. 25:515-517.
3. Baba, M., H. Tanaka, E. De Clercq, R. Pauwels, J. Balzarini, D. Schols, H. Nakashima, C.-F. Perno, R. T. Walker, and T. Miyasaka. 1989. Highly specific inhibition of human immunodeficiency virus type 1 by a novel 6-substituted acyclouridine derivative. Biochem. Biophys. Res. Commun. 165: 1375-1381.
4. Baba, M., E. De Clercq, H. Tanaka, M. Ubasawa, H. Takashima, K. Sekiya, I. Nitta, K. Umezu, H. Nakashima, S. Mori, S. Shigeta, R. T. Walker, and T. Miyasaka. 1991. Potent and selective inhibition of human immunodeficiency virus type 1 (HIV-1) by 5-ethyl-6-phenylthiouracil derivatives through their interaction with the HIV-1 reverse transcriptase. Proc. Natl. Acad. Sci. USA 88:2356-2360.
5. Baba, M., E. De Clercq, H. Tanaka, M. Ubasawa, H. Takashima, K. Sekiya, I. Nitta, K. Umezu, R. T. Walker, S. Mori, M. Ito, S. Shigeta, and T. Miyasaka. 1991. Highly potent and selective inhibition of human immunodeficiency virus type 1 by a novel series of 6-substituted acyclouridine derivatives. Mol. Pharmacol. 39:805-810.
6. Bader, J. P., J. B. McMahoo, R. J. Schultz, V. L. Narayanan, J. B. Pierce, W. A. Harrison, O. S. Weislow, C. F. Midelfort, S. F. Stinson, and M. R. Boyd. 1991. Oxathiin carboxanilide, a potent inhibitor of human immunodeficiency virus reproduction. Proc. Natl. Acad. Sci. USA 88:6740-6744.
7. Balzarini, J., M.-J. Pérez-Pérez, A. San-Félix, D. Schols, C.-F. Perno, A.-M. Vandamme, M.-J. Camarasa, and E. De Clercq. 1992. 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.
8. Balzarini, J., M.-J. Pérez-Pérez, A. San-Félix, S. Velázquez, M.-J. Camarasa, and E. De Clercq. 1992. [2′,5′-Bis-O-(tert-buryldimethylsilyl)]-3′-spiro-5″- (4″-amino-1″,2″-oxathiole-2″,2″-dioxide) (TSAO) derivatives of purine and pyrimidine nucleosides as potent and selective inhibitors of human immunodeficiency virus type 1. Antimicrob. Agents Chemother. 36:1073-1080.
9. Balzarini, J., A. Karlsson, and E. De Clercq. 1993. Human immunodeficiency virus type 1 drug resistance patterns with different 1-(2-hydroxyethoxy)methyl-6-(phenylthio)thymine derivatives. Mol. Pharmacol. 44:694-701.
10. Balzarini, J., A. Karlsson, M.-J. Pérez-Pérez, M.-J. Camarasa, and E. De Clercq. 1993. Knocking-out concentrations of HIV-1-specific inhibitors completely suppress HIV-1 infection and prevent the emergence of drug-resistant virus. Virology 196:576-585.
11. Balzarini, J., A. Karlsson, M.-J. Pérez-Pérez, M.-J. Camarasa, W. G. Tarpley, and E. De Clercq. 1993. Treatment of human immunodeficiency virus type 1 (HIV-1)-infected cells with combinations of HIV-1-specific inhibitors result in a different resistance pattern than does treatment with single-drug therapy. J. Virol. 67:5353-5359.
12. Balzarini, J., A. Karlsson, M.-J. Pérez-Pérez, L. Vrang, J. Walbers, H. Zhang, B. Oberg, A.-M. Vandamme, M.-J. Camarasa, and E. De Clercq. 1993. HIV-1-specific reverse transcriptase inhibitors show differential activity against HIV-1 mutant strains containing different amino acid substitutions in the reverse transcriptase. Virology 192:246-253.
13. Balzarini, J., A. Karlsson, A.-M. Vandamme, M.-J. Pérez-Pérez, H. Zhang, L. Vrang, B. Öberg, K. Bäckbro, T. Unge, A. San-Félix, S. Velázquez, M.-J. Camarasa, and E. De Clercq. 1993. 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 nonnucleoside inhibitors. Proc. Natl. Acad. Sci. USA 90:6952-6956.
14. Barré-Sinoussi, F., J. C. Chermann, F. Rey, M. T. Nugeyre, S. Chamaret, J. Gruest, C. Dauguet, C. Axler-Blin, F. Vézinet-Brun, C. Rouzioux, W. Rozenbaum, and L. Montagnier. 1983. Isolation of a T-lymphotropic retrovirus from a patient at risk for AIDS. Science 220:868-871.
15. Daniel, M. D., N. L. Letvin, P. K. Sehgal, G. Hunsmann, D. K. Schmidt, N. W. King, and R. C. Desrosiers. 1987. Long-term persistent infection of macaque monkeys with the simian immunodeficiency virus. J. Gen. Virol. 68:3183-3189.
16. Debyser, Z., R. Pauwels, K. Andries, J. Desmyter, M. Kukla, P. A. J. Janssen, and E. De Clercq. 1991. An antiviral target on reverse transcriptase of human immunodeficiency virus type 1 revealed by tetrahydroimidazo[4,5,1-jk] [1,4]benzodiazepin-2(1H)-one and thione derivatives. Proc. Natl. Acad. Sci. USA 88:1451-1455.
17. De Clercq, E. 1996. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) for the treatment of human immunodeficiency virus type 1 (HIV-1) infections: strategies to overcome drug resistance development. Med. Res. Rev. 16:125-157.
18. De Clercq, E. 1996. What can be expected from non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the treatment of human immunodeficiency virus type 1 (HIV-1) infections? Rev. Med. Virol. 6:97-117.
19. Dueweke, T. J., T. Pushkarskaya, S. M. Poppe, S. M. Swaney, J. Q. Zhao, I. S. Y. Chen, M. Stevenson, and W. G. Tarpley. 1993. A mutation in reverse transcriptase of bis(heteroaryl)piperazine-resistant human immunodeficiency virus type 1 that confers increased sensitivity to other nonnucleoside inhibitors. Proc. Natl. Acad. Sci. USA 90:4713-4717.
20. Elion, G. B., S. Singer, and G. H. Hitchings. 1954. Antagonists of nucleic acid derivatives. VIII. Synergism in combination of biochemically related antimetabolites. J. Biol. Chem. 208:477-488.
21. Esnouf, R. M. 1997. An extensively modified version of MolScript which includes greatly enhanced colouring capabilities. J. Mol. Graphics 15:132-134.
22. Esnouf, R. M., J. Ren, A. L. Hopkins, C. K. Ross, E. Y. Jones, D. K. Stammers, and D. I. Stuart. 1997. Unique features in the structure of the complex between HIV-1 reverse transcriptase and the bis(heteroaryl)piperazine U-90152 explain resistance mutations for this nonnucleoside inhibitor. Proc. Natl. Acad. Sci. USA 94:3984-3989.
23. Esnouf, R. M, D. I. Stuart, E. De Clercq, E. Schwartz, and J. Balzarini. 1997. Models which explain the inhibition of reverse transcriptase by HIV-1-specific (thio)carboxanilide derivatives. Biochem. Biophys. Res. Commun. 234:458-464.
24. Ferrin, T. E., C. C. Huang, L. E. Jarvis, and R. Langridge. 1988. The MIDAS display system. J. Mol. Graphics 6:13-27.
25. Foley, G. E., H. Lazarus, S. Farber, B. G. Uzman, B. A. Boone, and R. E. McCarthy. 1965. Continuous culture of human lymphoblasts from peripheral blood of a child with acute leukemia. Cancer 18:522-529.
26. Gallo, R. C., S. Z. Salahuddin, M. Popovic, G. M. Shearer, M. Kaplan, B. F. Haynes, T. J. Palker, R. Redfield, J. Oleske, and B. Safai. 1984. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science 224:500-503.
27. Goldman, M. E., J. H. Nunberg, J. A. O'Brien, J. C. Quintero, W. A. Schleif, K. F. Fruend, S. L. Gaul, W. S. Saari, J. S. Wai, J. M. Hoffman, P. S. Anderson, D. J. Hupe, E. A. Emini, and A. M. Stern. 1991. Pyridinone derivatives: specific human immunodeficiency virus type 1 reverse transcriptase inhibitors with antiviral activity. Proc. Natl. Acad. Sci. USA 88:6863-6867.
28. Goldman, M. E., J. A. O'Brien, T. L. Ruffing, J. H. Nunberg, W. A. Schleif, J. C. Quintero, P. K. S. Siegl, J. M. Hoffman, A. M. Smith, and E. A. Emini. 1992. L-696,229 specifically inhibits human immunodeficiency virus type 1 reverse transcriptase and possesses antiviral activity in vitro. Antimicrob. Agents Chemother. 36:1019-1023.
29. Hopkins, A. L., J. Ren, R. M. Esnouf, B. E. Willcox, E. Y. Jones, C. Ross, T. Miyasaka, R. T. Walker, H. Tanaka, D. K. Stammers, and D. I. Stuart. 1996. Complexes of HIV-1 reverse transcriptase with inhibitors of the HEPT series reveal conformational changes relevant to the design of potent non-nucleoside inhibitors. J. Med. Chem. 39:1589-1600.
30. Kleim, J.-P., R. Bender, U.-M. Billhardt, C. Meichsner, G. Riess, M. Rösner, I. Winkler, and A. Paessens. 1993. Activity of a novel quinoxaline derivative against human immunodeficiency virus type 1 reverse transcriptase and viral replication. Antimicrob. Agents Chemother. 37:1659-1664.
31. Kraulis, P. J. 1991. MolScript: a program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24:946-950.
32. Larder, B. A., and S. D. Kemp. 1989. Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT). Science 246: 1155-1158.
33. Merluzzi, V. J., K. D. Hargrave, M. Labodia, K. Grozinger, M. Skoog, J. C. Wu, C.-K. Shin, K. Eckner, S. Hattox, J. Adams, A. S. Rosenthal, R. Faanes, R. J. Eckner, R. A. Koup, and J. L. Sullivan. 1990. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science 250: 1411-1413.
34. Miyasaka, T., H. Tanaka, M. Baba, H. Hayakawa, R. T. Walker, J. Balzarini, and E. De Clercq. 1989. A novel lead for specific anti-HIV-1 agents: 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine. J. Med. Chem. 32:2507-2509.
35. Miyoshi, I., H. Taguchi, I. Kobonishi, S. Yoshimoto, Y. Ohtsuki, Y. Shiraishi, and T. Agaki. 1982. Type C virus-producing cell lines derived from adult T cell leukemia. Gann Monogr. 28:219-228.
36. Mohamadi, F., N. G. J. Richards, W. C. Guida, R. Liskamp, M. Lipton, C. Caufield, G. Chang, T. Hendrickson, and W. C. Still. 1990. Macro-Model - an integrated software system for modeling organic and bioorganic molecules using molecular mechanics. J. Comput. Chem. 11:440-467.
37. Pauwels, R., E. De Clercq, J. Desmyter, J. Balzarini, P. Goubau, P. Herdewijn, H. Vanderhaeghe, and M. Vandeputte. 1987. Sensitive and rapid assay on MT-4 cells for the detection of antiviral compounds against the AIDS virus. J. Virol. Methods 16:171-185.
38. Pauwels, R., J. Balzarini, M. Baba, R. Snoeck, D. Schols, P. Herdewijn, J. Desmyter, and E. De Clercq. 1988. Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds. J. Virol. Methods 20:309-321.
39. Pauwels, R., K. Andries, J. Desmyter, D. Schols, M. J. Kukla, H. J. Breslin, A. Raeymaeckers, J. Van Gelder, R. Woestenborghs, J. Heykants, K. Schellekens, M. A. C. Janssen, E. De Clercq, and P. A. J. Janssen. 1990. Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives. Nature 343:470-474.
40. Pauwels, R., K. Andries, Z. Debyser, P. Van Daele, D. Schols, P. Stoffels, K. De Vreese, R. Woestenborghs, A.-M. Vandamme, C. G. M. Janssen, J. Anné, G. Cauwenbergh, J. Desmyter, J. Heykants, M. A. C. Janssen, E. De Clercq, and P. A. J. Janssen. 1993. Potent and highly selective human immunodeficiency virus type 1 (HIV-1) inhibition by a series of α-anilinophenylacetamide derivatives targeted at HIV-1 reverse transcriptase. Proc. Natl. Acad. Sci. USA 90:1711-1715.
41. Pearlman, D. A., D. A. Case, J. W. Caldwell, W. S. Ross, T. E. Cheatham, D. M. Ferguson, G. L. Seibel, U. C. Singh, P. K. Weiner, and P. A. Kollman. 1995. AMBER 4.1, University of California, San Francisco, Calif.
42. Popovic, M., M. G. Saragadharan, E. Read, and R. C. Gallo. 1984. Detection, isolation and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224:497-500.
43. Ren, J., R. Esnouf, E. Garman, D. Somers, C. Ross, J. Kirby, J. Keeling, G. Darby, Y. Jones, D. Stuart, and D. Stammers. 1995. High resolution structures of HIV-1 RT from four RT-inhibitor complexes. Nature Struct. Biol. 2:293-302.
44. Romero, D. L., M. Busso, C.-K. Tan, F. Reusser, J. R. Palmer, S. M. Poppe, P. A. Aristoff, K. M. Downey, A. G. So, L. Resnick, and W. G. Tarpley. 1991. Nonnucleoside reverse transcriptase inhibitors that potently and specifically block human immunodeficiency virus type 1 replication. Proc. Natl. Acad. Sci. USA 88:8806-8810.
45. Romero, D. L., R. A. Morge, M. J. Genin, C. Biles, M. Busso, L. Resnick, I. W. Althaus, F. Reusser, R. C. Thomas, and W. G. Tarpley. 1993. Bis(heteroaryl-piperazine (BHAP) reverse transcriptase inhibitors: structure-activity relationships of novel substituted indole analogues and the identification of 1-[(5-methanesulfonamido-1H-indol-2-yl)-carbonyl]-4-[3[(1-methylethyl)-amino] pyridinyl]piperazine monomethanesulfonate (U-90152S), a second-generation clinical candidate. J. Med. Chem. 36:1505-1508.
46. Schinazi, R. F., B. A. Larder, and J. W. Mellors. 1996. Mutations in retroviral genes associated with drug resistance. Int. Antiviral News 4:95-107.
47. Schols, D., M. Baba, R. Pauwels, J. Desmyter, and E. De Clercq. 1989. Specific interaction of aurintricarboxylic acid with the human immunodeficiency/CD4 cell receptor. Proc. Natl. Acad. Sci. USA 86:3322-3326.
48. Spire, B., J. Sire, V. Zachar, F. Rey, F. Barré-Sinoussi, F. Galibert, A. Hampe, and J. C. Chermann. 1989. Nucleotide sequence of HIV1-NDK: a highly cytopathic strain of human immunodeficiency virus. Gene 81:275-284.
49. St. Clair, M. H., J. L. Martin, G. Tudor-Williams, M. C. Bach, C. L. Vavro, D. M. King, P. Kellam, S. D. Kemp, and B. A. Larder. 1991. Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase. Science 253:1557-1559.
50. Tisdale, M., S. D. Kemp, N. R. Parry, and B. A. Larder. 1993. Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3′-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. Proc. Natl. Acad. Sci. USA 90:5653-5656.
51. Witvrouw, M., J. Balzarini, C. Pannecouque, S. Jhaumeer-Laulloo, J. A. Esté, D. Schols, P. Cherepanov, J.-C. Schmit, Z. Debyser, A.-M. Vandamme, J. Desmyter, S. R. Ramadas, and E. De Clercq. 1997. SRR-SB3, a disulfidecontaining macrolide that inhibits a late stage of the replicative cycle of human immunodeficiency virus. Antimicrob. Agents Chemother. 41:262-268.
52. Wu, J. C., T. C. Warren, J. Adams, J. Proudfoot, J. Skils, P. Raghavan, C. Perry, J. Pataki, P. R. Forina, and P. M. Grob. 1991. A novel dipyridodiazepinone inhibitor of HIV-1 reverse transcriptase acts through a nonsubstrate binding site. Biochemistry 30:2022-2026.