Highly favorable antiviral activity and resistance profile of the novel thiocarboxanilide pentenyloxy ether derivatives UC-781 and UC-82 as inhibitors of human immunodeficiency virus type 1 replication

Molecular Pharmacology

Volumn 50, Issue 2, 1996, Pages 394-401

  Balzarini, J ^a   Pelemans, H ^a   Aquaro, S ^b   Perno, C F ^b   Witvrouw, M ^a   Schols, D ^a   De Clercq, E ^a   Karlsson, A ^c  

^a REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^b UNIVERSITY OF ROME TOR VERGATA   (Italy)

^c KAROLINSKA INSTITUTE   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; DELAVIRDINE; N [4 CHLORO 3 (3 METHYL 2 BUTENYLOXY)PHENYL] 2 METHYL 3 FURANCARBOTHIOAMIDE; N [4 CHLORO 3 (3 METHYL 2 BUTENYLOXY)PHENYL] 2 METHYL 3 THIOPHENECARBOTHIOAMIDE; NEVIRAPINE; THIOCARBOXANILIDE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANTIVIRAL ACTIVITY; ARTICLE; DRUG CONFORMATION; DRUG POTENCY; DRUG RESISTANCE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MOUSE; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION; VIRUS INHIBITION; VIRUS MUTATION; VIRUS REPLICATION;

ANILIDES; ANTIVIRAL AGENTS; BASE SEQUENCE; BLOOD PROTEINS; CELLS, CULTURED; DELAVIRDINE; DRUG RESISTANCE; FURANS; HIV-1; HIV-1 REVERSE TRANSCRIPTASE; HUMANS; INDOLES; MOLECULAR SEQUENCE DATA; PIPERAZINES; PROTEIN BINDING; RNA-DIRECTED DNA POLYMERASE; THIOPHENES; VIRUS REPLICATION;

EID: 0029809694     PISSN: 0026895X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (27)

1. De Clercq, E. HIV resistance to reverse transcriptase inhibitors. Biochem. Pharmacol. 47:155-169 (1994).
2. De Clercq, E. Non-nucleoside reverse transcriptase inhibitors (NNRTIs). Exp. Opin. Invest. Drugs 3:253-271 (1994).
3. De Clercq, E. Antiviral therapy for human immunodeficiency virus infections. Clin. Microbiol. Rev. 8:200-239 (1995).
4. De Clercq, E. Toward improved anti-HIV chemotherapy: therapeutic strategies for intervention with HIV infections. J. Med. Chem. 38:2491-2517 (1995).
5. Mellors, J. W., B. A. Larder, and R. F. Schinazi. Mutations in HIV-1 reverse transcriptase and protease associated with drug resistance. Int. Antiviral News 3:8-13 (1995).
6. Balzarini, J., H. Jonckheere, W. A. Harrison, D. C. Dao, J. Anné, E. De Clercq, and A. Karlsson. Oxathiin carboxanilide derivatives: a class of non-nucleoside HIV-1-specific reverse transcriptase inhibitors (NNRTIs) that are active against mutant HIV-1 strains resistant to other NNRTIs. Antiviral Chem. Chemother. 6:169-178 (1995).
7. Balzarini, J., W. G. Brouwer, E. E. Felauer, E. De Clercq, and A. Karlsson. Activity of various thiocarboxanilide derivatives against wild-type and several mutant human immunodeficiency virus type 1 strains. Antiviral Res. 27:219-236 (1995).
8. Balzarini, J., M.-J. Pérez-Pérez, S. Velázquez, A. San-Félix, M.-J. Camarasa, E. De Clercq, and A. Karlsson. Suppression of the breakthrough of human immunodeficiency virus type (HIV-1) in cell culture by thiocarboxanilide derivatives when used individually or in combination with other HIV-1-specific inhibitors (i.e., TSAO derivatives). Proc. Natl. Acad. Sci. USA 92:5470-5474 (1995).
9. Ba-L) replication in fresh and cultured human peripheral blood monocytes/ macrophages by azidothymidine and related 2′,3′-dideoxynucleosides. J. Exp. Med. 168:1111-1125 (1988).
10. Popovic, M., M. G. Sarngadharan, E. Read, and R. C. Gallo. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science (Washington D. C.) 224: 497-500 (1984).
11. Balzarini, J., A. Karlsson, M.-J. Pérez-Pérez, L. Vrang, J. Walbers, H. Zhang, B. Öberg, A.-M. Vandamme, M.-J. Camarasa, and E. De Clercq, E. 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 (1993).
12. 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. Velázquet, M.-J. Camarasa, and E. De Clercq. 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 (1993).
13. Balzarini, J., A. Karlsson, M.-J. Pérez-Pérez, 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 result in a different resistance pattern than does treatment with single-drug therapy. J. Virol 67:5353-5359 (1993).
14. Balzarini, J., M.-J. Pérez-Pérez, A. San-Félix, M.-J. Camarasa, I. C. Bathurst, P. J. Barr, and E. De Clercq. 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)-β-D-ribofuranosyl]- 3′-spiro-5″-(4″-amino-1″,2″-oxathiole-2″, 2″-dioxide). thymine (TSAO-T). J. Biol. Chem. 267:11831-11838 (1992).
15. Mosier, D. E., R. J. Gulizia, S. M. Baird, D. B. Wilson, D. H. Spector, and S. A. Spector. Human immunodeficiency virus infection of human-PBL-SCID mice. Science (Washington D. C.) 251:791-794 (1991).
16. + T cells in human-PBL-SCID míce by noncytopathic HIV isolates. Science (Washington D. C.) 260:689-692 (1993).
17. Bader, J. P., J. B. McMahon, 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. Oxathiin carboxanilide, a potent inhibitor of human immunodeficiency virus reproduction. Proc. Natl. Acad. Sci. USA 88:6740-6744 (1991).
18. De Clercq, E., A. Karlsson, and J. Balzarini. Thiocarboxanilides: a new class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) with great potential for the treatment of human immunodeficiency virus type 1 (HIV-1) infections, in Advanced Medicinal Chemistry: Modern Approaches in Drug Design. Thessaloniki, Greece (1996).
19. Balzarini, J., W. G. Brouwer, D. C. Dao, E. M. Osika, and E. De Clercq. Identification of novel thiocarboxanilide derivatives that suppress a variety of drug-resistant mutant human immunodeficiency virus type 1 (HIV-1) strains at a similar potency as wild-type virus. Antimicrob. Agents Chemother. 40:1454-1466 (1996).
20. Byrnes, V. W., W. Sardana, W. A. Schleif, J. H. Condra, J. A. Waterbury, J. A. Wolfgang, W. J. Long, C. L. Schneider, A. J. Schlabach, B. S. Wolanski, D. J. Graham, L. Gotlib, A. Rhodes, D. L. Titus, E. Roth, O. M. Blahy, J. C. Quintero, S. Staszewski, and E. A. Emini. Comprehensive mutant enzyme and viral variant assessment of human immunodeficiency virus type-1 reverse transcriptase resistance to non-nucleoside inhibitors. Antimicrob. Agents Chemother. 37:1576-1579 (1993).
21. Ahgren, C., K. Backbro, 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, Jr., M. A. Muesing, R. Noreen, B. Öberg, 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. The PETT series, a new class of potent non-nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. Antimicrob. Agents Chemother. 39:1329-1335 (1995).
22. Mellors, J. W., G. J. Im, E. Tramontano, S. R. Winkler, D. J. Medina, G. E. Dutschman, H. Z. Bazmi, G. Piras, C. J. Gonzalez, and Y.-C. Cheng. A single conservative amino acid substitution in the reverse transcriptase of human immunodeficiency virus-1 confers resistance to (+)-(5S)4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-butenyl)imidazo[4,5,1-jk][11, 4]benzodiazepin-2(1H)-thione (TIBO R82150). Mol. Pharmacol. 43: 1-16 (1993).
23. Larder, B. A. 3′-Azido-3′-deoxythymidine resistance suppressed by a mutation conferring human immunodeficiency virus type 1 resistance to non-nucleoside reverse transcriptase inhibitors. Antimicrob. Agents Chemother. 36:2664-2669 (1992).
24. Richman, D., D. Havlir, J. Corbeil, D. Looney, C. Ignacio, S. A. Spector, J. Sullivan, S. Cheeseman, K. Barringer, D. Pauletti, C. K. Shih, M. Myers, and J. Griffin. Nevirapine resistance mutations of human immunodeficiency virus type 1 selected during therapy. J. Virol. 68:1660-1666 (1994).
25. Ho, D. D., A. U. Neumann, A. S. Perelson, W. Chen, J. M. Leonard, and M. Markowitz. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature (Lond.) 373:123-126 (1995).
26. Wei, X., S. K. Ghosh, M. E. Taylor, V. A. Johnson, E. A. Emini, P. Deutsch, J. D. Lifson, S. Bonhoeffer, M. A. Nowak, B. H. Hahn, M. S. Saag, and G. M. Shaw. Viral dynamics in human immunodeficiency virus type 1 infection. Nature (Lond.) 373:117-122 (1995).
27. + T cell repertoire in hu-PBL-SCID chimeras. J. Exp. Med. 180:1817-1827 (1994).