Urea-PETT compounds as a new class of HIV-1 reverse transcriptase inhibitors. 3. Synthesis and further structure-activity relationship studies of PETT analogues

Journal of Medicinal Chemistry

Volumn 42, Issue 20, 1999, Pages 4150-4160

  Högberg, Marita ^a   Sahlberg, Christer ^a   Engelhardt, Per ^a   Noréen, Rolf ^a   Kangasmetsä, Jussi ^a   Johansson, Nils Gunnar ^a   Öberg, Bo ^a,b   Vrang, Lotta ^a   Zhang, Hong ^a   Sahlberg, Britt Louise ^a   Unge, Torsten ^c,d   Lövgren, Seved ^c   Fridborg, Kerstin ^c   Bäckbro, Kristina ^c  

^a MEDIVIR AB   (Sweden)

^b KAROLINSKA INSTITUTE   (Sweden)

^c UPPSALA UNIVERSITY   (Sweden)

^d UPPSALA UNIVERSITY   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

PHENYLETHYLTHIAZOLYLTHIOUREA DERIVATIVE; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG; UREA DERIVATIVE;

ALLOSTERISM; ANTIVIRAL ACTIVITY; ARTICLE; DRUG STRUCTURE; ENANTIOMER; HUMAN IMMUNODEFICIENCY VIRUS 1; RACEMIC MIXTURE; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ADMINISTRATION, ORAL; AMINOPYRIDINES; ANIMALS; ANTI-HIV AGENTS; BIOLOGICAL AVAILABILITY; CRYSTALLOGRAPHY, X-RAY; DRUG RESISTANCE, MICROBIAL; HIV-1; INJECTIONS, INTRAVENOUS; MALE; MODELS, MOLECULAR; MOLECULAR CONFORMATION; RATS; REVERSE TRANSCRIPTASE INHIBITORS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; UREA;

EID: 0037679871     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990095j     Document Type: Article

References (39)

1. Hirsch, M. S. Current antiretrovirals - a review. Antiviral Ther. 1997, 2 (Suppl. 4), 19-40.
2. (a) Grob, P. M.; Wu, J. C.; Cohen, K. A.; Ingraham, R. H.; Shih, C. K.; Hargrave, K. D.; McTague, T. L.; Merluzzi, V. J. Non-nucleoside Inhibitors of HIV-1 Reverse Transcriptase: Nevirapine as a Prototype Drug. AIDS Res. Hum. Retroviruses 1992, 8, 145-52.
3. (b) Hargrave, K. D:; Proudfood, J. R.; Grozinger, K. G.; Cullen, E.; Kapadia, S. R.; Patel, U. R.; Fuchs, V. U.; Mauldin, S. C.; Vitous, J.; Behnke, M. L.; Klunder, J. M.; Pal, K.; Skiles, J. W.; McNeil, D. W.; Rose, J. M.; Chow, G. C.; Skoog, M. T.; Wu, J. C.; Schmidt, G.; Engel, W. W.; Eberlein, W. G.; Saboe, T. D.; Campbell, S. J.; Rosenthal, A. S.; Adams, J. Novel Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase. 1. Tricyclic Pyridobenzo-and Dipyridodiazepinones. J. Med. Chem. 1991, 34, 2231-2241.
4. (c) Cheeseman, S. H.; Hattox, S. E.; McLaughlin, M. M.; Koup, R. A.; Andrews, C. A.; Bova, C. A.; Pav, J. W.; Roy, T.; Sullivan, J. L.; Keirns, J. J. Pharmacokinetics of Nevirapine: Initial Single-Rising-Dose Study in Humans. Antimicrob. Agents Chemother. 1993, 37, 178-182.
5. (d) Carr, A.; Vella, S.; de Jong, M. D.; Sorice, F.; Imrie, A.; Boucher, C. A.; Cooper, D. A. A controlled trial of nevirapine plus zidovudine versus zidovudine alone in p24 antigenaemic HIV-infected patients. AIDS 1996, 10, 635-641.
6. (a) Romero, D. L.; Morge, R. A.; Biles, C.; Berrios-Péna, 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.; Aristoff, P. A. Discovery, Synthesis, and Bioactivity of Bis(heteroaryl)-piperazines. 1. A Novel Class of Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors. J. Med. Chem. 1994, 37, 999-1014.
7. (b) Davey Jr., R. T.; Chaitt, D. G.; Reed, G. F.; Freimuth, W. W.; Herpin, B. R.; Metcalf, J. A.; Eastman, P. S.; Falloon, J.; Kovacs, J. A.; Polis, M. A.; Walker, R. E.; Masur, H.; Boyle, J.; Coleman, S.; Cox, S. R.; Wathen, L.; Daenzer, C. L.; Lane, H. C. Randomized, Controlled Phase I/II Trial of Combination Therapy with Delavirdine (U-90152S) and Conventional Nucleosides in Human Immunodeficiency Virus Type 1-Infected Patients. Antimicrob. Agents Chemother. 1996, 40, 1657-1664.
8. Young, S. D.; Britcher, S. F.; Tran, L. O.; Payne, L. S.; Lumma, W. C.; Lyle, T. A.; Huff, J. R.; Anderson, P. S.; Olsen, D. B.; Carroll, S. S.; Pettibone, D. J.; O'Brien, J. A.; Ball, R. G.; Balani, S. K.; Lin, J. H.; Chen, I.-W.; Schleif, W. A.; Sardana, V. V.; Long, W. J.; Byrnes, V. W.; Emini, E. A. L-743,726 (DMP-266): a Novel, Highly Potent Nonnucleoside Inhibitor of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase. Antimicrob. Agents Chemother. 1995, 39, 2602-2605.
9. Kleim, J.-P.; Bender, R.; Kirsch, R.; Meichsner, C.; Paessens, A.; Rösner, M.; Rübsamen-Waigmann, H.; Kaiser, R.; Wichers, M.; Schneweis, K. E.; Winkler, I.; Riess, G. Preclinical Evaluation of HBY 097, a New Nonnucleoside Reverse Transcriptase Inhibitor of Human Immunodeficiency Virus Type 1 Replication. Antimicrob. Agents Chemother. 1995, 39, 2253-2257.
10. (a) Pauwels, R.; Andries, K.; Debyser, Z.; Van Daele, P.; Schols, D.; Stoffels, P.; De Vreese, K.; Woestenborghs, R.; Vandamme, A.-M.; Janssen, C. G. M.; Anne, J.; Cauwenbergh, G.; Desmyter, J.; Heykants, J.; Janssen, M. A. C.; De Clercq, E.; Janssen, P. A. J. Potent and Highly Selective Human Immunodeficiency Virus Type 1 (HIV-1) Inhibition by a Series of Alpha-anilinophenylacetamide Derivatives Targeted at HIV-1 Reverse Transcriptase. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 1711-1715.
11. (b) Staszewski, S.; Miller, V.; Rehmet, S.; Stark, T.; De Crée, J.; De Brabander, M.; Peeters, M.; Andries, K.; Moeremans; M., De Raeymaeker, M.; Pearce, G.; Van Den Broeck, R.; Verbiest, W.; Stoffels, P. Virological and immunological analysis of a triple combination pilot study with loviridine, lamivudine and zidovudine in HIV-infected patients. AIDS 1996, 10, F1-F7.
12. Pauwels, R.; Andries, K.; Debyser, Z.; Kukla, M. J.; Schols, D.; Breslin, H. J.; Woestenborghs, R.; Desmyter, J.; Janssen, M. A. C.; De Clercq, E.; Janssen, P. A. J. New Tetrahydroimidazo[4,5,1-jk][1,4]-Benzodiazepin-2(1H)-One and -Thione Derivatives Are Potent Inhibitors of Human Immunodeficiency Virus Type 1 Replication and Are Synergistic with 2′,3′-Dideoxynucleoside Analogues. Antimicrob. Agents Chemother. 1994, 38, 2863-2870.
13. Okamoto, M.; Makino, M.; Yamada, K.; Nakade, K.; Yuasa, S.; Baba, M. Complete inhibition of viral breakthrough by combination of MKC-442 with AZT during a long-term culture of HIV-1-infected cells. Antiviral Res. 1996, 31, 69-77.
14. Cushman, M.; Golebiewski, W. M.; Graham, L.; Turpin, J. A.; Rice, W. G.; Fliakas-Boltz, V.; Buckheit, Jr., R. W. Synthesis and Biological Evaluation of Certain Alkenyldiarylmethanes as Anti-HIV-1 Agents Which Act as Non-Nucleoside Reverse Transcriptase Inhibitors. J. Med. Chem. 1996, 39, 3217-3227.
15. Fujiwara, T.; Sato, A.; El-Farrash, M.; Miki, S.; Abe, K.; Isaka, Y.; Kodama, M.; Wu, Y.; Chen, L. B.; Harada, H.; Sugimoto, H.; Hatanaka, M.; Hinuma, Y. S-1153 Inhibits Replication of Known Drug-Resistant Strains of Human Immunodeficiency Virus Type 1. Antimicrob. Agents Chemother. 1998, 42, 1340-1345.
16. Balzarini, J.; Brouver, W. G.; Dao, D. C.; Osika, E. M.; De Clercq, E. Identification of Novel Thiocarboxanilide Derivatives That Suppress a Variety of Drug-Resistant Mutant Human Immunodeficiency Virus Type 1 Strains at a Potency Similar to That for Wild-Type Virus. Antimicrob. Agents Chemother. 1996, 40, 1454-1466.
17. (a) Richman, D. D. Drug resistance and its implications in the management of HIV infection. Antiviral Ther. 1997, 2 (Suppl. 4), 41-58.
18. (b) Jeffrey, S.; Corbett, J.; Bacheler, L. In Vitro NNRTI Resistance of Recombinant HIV-Carrying Mutations Observed in Efavirenz Treatment Failures. 6th Conference on Retroviruses and Opportunistic Infections, Chicago, IL, Feb 1-5, 1999; Abstract 110.
19. Schooley, R. T. Changing treatment strategies and goals. Antiviral Ther. 1997, 2 (Suppl. 4), 59-70.
20. Zhang, H.; Vrang, L.; Rydegård, C.; Åhgren, C.; Öberg, B. Synergistic inhibition of HIV-1 reverse transcriptase and HIV-1 replication by combining trovirdine with AZT, ddI and ddC in vitro. Antiviral Chem. Chemother. 1996, 7, 221-229.
21. Lange, J. Issues for the future of antiretroviral therapy. Antiviral Ther. 1997, 2 (Suppl. 4), 71-83.
22. de Jong, M. D.; Boucher, C. A. B.; Galasso, G. J.; Hirsch, M. S.; Kern, E. R.; Lange, J. M. A.; Richman, D. D. Consensus symposium on combined antiviral therapy. Antiviral Res. 1995, 29, 5-29.
23. Ahgren, C.; Backro, K.; Bell, F. W.; Cantrell, A. S.; Clemens, M.; Colacino, J. M.; Deeter, J. B.; Engelhardt, J. A.; Hogberg, M.; Jaskunas, S. R.; Johansson, N. G.; Jordan, C. L.; Kasher, J. S.; Kinnick, M. D.; Lind, P.; Lopez, C.; Morin, Jr., J. M.; Muesing, M. A.; Noreen, R.; Oberg, B.; Paget, C. J.; Palkowitz, J. A.; Parrish, C. A.; Pranc, P.; Rippy, M. K.; Rydergard, C.; Sahlberg, C.; Swanson, S.; Ternansky, R. J.; Unge, T.; Vasileff, R. T.; Vrang, L.; West, S. J.; Zhang, H.; Zhou, X.-X. The PETT Series, a New Class of Potent Nonnucleoside Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase. Antimicrob. Agents Chemother. 1995, 39, 1329-1335.
24. Bell, F. W.; Cantrell, A. S.; Högberg, M.; Jaskunas, S. R.; Johansson, N. G.; Jordan, C. L.; Kinnick, M. D.; Lind, P.; Morin, Jr. J. M.; Noréen, R.; Öberg, B.; Palkowitz, J. A.; Parrish, C. A.; Pranc, P.; Sahlberg, C.; Ternansky, R. J.; Vasileff, R. T.; Vrang, L.; West, S. J.; Zhang, H.; Zhou, X.-X. Phenethylthiazolethiourea (PETT) Compounds, a New Class of HIV-1 Reverse Transcriptase Inhibitors. 1. Synthesis and Basic Structure-Activity Relationship Studies of PETT Analogues. J. Med. Chem. 1995, 38, 4929-4936.
25. Zhang, H.; Vrang, L.; Bäckbro, K.; Lind, P.; Sahlberg, C.; Unge, T.; Öberg, B. Inhibition of human immunodeficiency virus type 1 wild-type and mutant reverse transcriptases by the phenyl ethyl thiazolyl thiourea derivatives trovirdine and MSC-127. Antiviral Res. 1995, 28, 331-342.
26. Cantrell, A. S.; Engelhardt, P.; Högberg, M.; Jaskunas, S. R.; Johansson, N. G.; Jordan, C. L.; Kangasmetsä, J.; Kinnick, M. D.; Lind, P.; Morin, Jr., J. M.; Muesing, M. A.; Noréen, R.; Öberg, B.; Pranc, P.; Sahlberg, C.; Ternansky, R. J.; Vasileff, R. T.; Vrang, L.; West, S. J., Zhang, H. Phenethylthiazolylthiourea (PETT) Compounds as a New Class of HIV-1 Reverse Transcriptase Inhibitors. 2. Synthesis and Further Structure-Activity Relationship Studies of PETT Analogues. J. Med. Chem. 1996, 39, 4261-4274.
27. Sahlberg, C.; Noréen, R.; Engelhardt, P.; Högberg, M.; Kangasmetsä, J.; Vrang, L.; Zhang, H. Synthesis and Anti-HIV Activities of Urea-PETT Analogues Belonging to a New Class of Potent Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors. Bioorg. Med. Chem. Lett. 1998, 8, 1511-1516.
28. Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. Bis-(oxazolines) as Chiral Ligands in Metal-Catalyzed Asymmetric Reactions. Catalytic, Asymmetric Cyclopropanation of Olefins. J. Am. Chem. Soc. 1991, 113, 726-728.
29. Zhang, H.; Vrang, L.; Unge, T.; Öberg, B. Characterization of HIV Reverse Transcriptase with Tyr181→Cys and Leu100→Ile Mutations. Antiviral Chem. Chemother. 1993, 4, 301-308.
30. Weislow, O. S.; Kiser, R.; Fine, D. L.; Bader, J.; Shoemaker, R. H.; Boyd, M. R. New Soluble-Formazan Assay for HIV-1 Cytopathic Effects: Application to High-Flux Screening of Synthetic and Natural Products for AIDS-Antiviral Activity. J. Natl. Cancer Inst. 1989, 81, 577-586.
31. Noréen, R.; Engelhardt, P.; Kangasmetsä, J.; Sahlberg, C.; Vrang, L.; Morin, Jr., J. M.; Ternansky, R. J.; Zhang, H. Conformationally Restricted Analogues of a New Class of Potent Non-Nucleoside Reverse Transcriptase Inhibitors. VIth International Conference on Antiviral Research, Venice, Italy, Apr 25-30, 1993; Abstract 69.
32. Noland, W. E. Organic Syntheses; John Wiley & Sons: New York, 1988; Collect. Vol. VI, p 739, note 10.
33. Gewirth, D.; Otwinovski, Z. The SCALEPACK manual; 1995.
34. Otwinovski, Z.; Minor, W. The HKL Program Suite.
35. i is an observation of the intensity of an individual reflection and 〈I〉 is the average intensity over symmetry equivalents.
36. Brünger, A. T.; Kuriyan, J.; Karplus, M. Crystallographic R factor refinement by molecular dynamics. Science 1987, 235, 458-460.
37. crystal but calculated for a randomly chosen set of reflections that were omitted from the refinement process.
38. Jones, T. A.; Zou, J.-Y.; Cowan, S. W.; Kjeldgaard, M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 1991, 47, 110-119.
39. Kraulis, P. J. MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 1991, 24, 946-950.