3-(1,1-dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones, potent inhibitors of hepatitis C virus RNA-dependent RNA polymerase

Journal of Medicinal Chemistry

Volumn 49, Issue 3, 2006, Pages 971-983

  Tedesco, Rosanna ^a   Shaw, Antony N ^a   Bambal, Ramesh ^a   Chai, Deping ^a   Concha, Nestor O ^a   Darcy, Michael G ^a   Dhanak, Dashyant ^a   Fitch, Duke M ^a   Gates, Adam ^a   Gerhardt, Warren G ^a   Halegoua, Dina L ^a   Han, Chao ^a   Hofmann, Glenn A ^a   Johnston, Victor K ^a   Kaura, Arun C ^a   Liu, Nannan ^a   Keenan, Richard M ^a   Lin Goerke, Juili ^a   Sarisky, Robert T ^a   Wiggall, Kenneth J ^a   Zimmerman, Michael N ^a   Duffy, Kevin J ^a   more..

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 (1,1 DIOXO 2H 1,2,4 BENZOTHIADIAZIN 3 YL) 4 HYDROXY 2(1H) QUINOLINONE; ENZYME INHIBITOR; QUINOLINE DERIVATIVE; RNA DIRECTED RNA POLYMERASE; UNCLASSIFIED DRUG; VIRUS RNA;

ARTICLE; DRUG POTENCY; DRUG SAFETY; ENZYME ACTIVITY; HEPATITIS C; HEPATITIS C VIRUS; HIGH THROUGHPUT SCREENING; REPLICON; VIRUS CHARACTERIZATION; VIRUS GENOME; VIRUS REPLICATION;

ANIMALS; ANTIVIRAL AGENTS; BENZOTHIADIAZINES; BIOLOGICAL AVAILABILITY; BLOOD PROTEINS; CELL LINE; CRYSTALLOGRAPHY, X-RAY; DOGS; GENOTYPE; HALF-LIFE; HEPACIVIRUS; MACACA FASCICULARIS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MUTATION; PROTEIN BINDING; QUINOLONES; RATS; RATS, SPRAGUE-DAWLEY; RNA REPLICASE; STRUCTURE-ACTIVITY RELATIONSHIP; THIADIAZINES;

EID: 32344448745     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050855s     Document Type: Article

References (24)

1. Choo, Q. L.; Kuo, G.; Weiner, A. J.; Overby, L. R.; Bradley, D. W.; Houghton, M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 1989, 244, 359-362.
2. CDC Hepatitis C Fact Sheet 2003 http://www.cdc.gov/ncidod/ diseases/hepatitis/c/cfact.pdf.
3. Saito, I.; Miyamura, T.; Ohbayashi, A.; Harada, H.; Katayama, T.; Kikuchi, S.; Watanabe, Y.; Koi, S.; Onji, M. Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 6547-6549.
4. Hugle, T.; Cerny, A. Current therapy and new molecular approaches to antiviral treatment and prevention of hepatitis C. Rev. Med. Virol. 2003, 13, 361-371.
5. Clough, J. A 'C' change for hepatitis treatment. Drug Discuss. Today 2002, 7, 335-336.
6. Harper, S.; Avolio, S.; Pacini, B.; Di Filippo, M.; Altamura, S.; Tomei, L.; Paonessa, G.; Di Marco, S.; Carfi, A.; Giuliano, C.; Padron, J.; Bonelli, F.; Migliaccio, G.; De Francesco, R.; Laufer, M.; Rowley, M.; Narjes, F. Potent inhibitors of subgenomic hepatatis C virus RNA replication through optimization of indole-N-acetamide allosteric inhibitors of the viral NS5B polymerase. J. Med. Chem. 2005, 48, 4547-4557 and references therein.
7. Condon, S. M.; LaPorte, M. G.; Herbertz, T. Allosteric inhibitors of Hepatitis C NS5B RNA-dependent RNA polymerase. Curr. Med. Chem.-Anti-Infective Agents 2005, 4, 99-110 and references therein.
8. Behrens, S. E.; Tomei, L.; de Francesco, R. Identification and properties of the RNA-dependent RNA polymerase of hepatitis C virus. EMBO J 1996, 15, 12-22.
9. de Francesco, R.; Behrens, S. E.; Tomei, L.; Altamura, S.; Jiricny, J. RNA-dependent RNA polymerase of hepatitis C virus. Methods Enzymol. 1996, 275, 58-67.
10. Ago, H.; Adachi, T.; Yoshida, A.; Yamamoto, M.; Habuka, N.; Yatsunami, K.; Miyano, M. Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. Structure Fold. Des. 1999, 7, 1417-1426.
11. Bressanelli, S.; Tomei, L.; Roussel, A.; Incitti, I.; Vitale, R. L.; Mathieu, M.; de Francesco, R.; Rey, F. A. Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. Proc Natl. Acad. Sci. U.S.A. 1999, 96, 13034-13039.
12. Lesburg, C. A.; Cable, M. B.; Ferrari, E.; Hong, Z.; Mannarino, A. F.; Weber, P. C. Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site. Nat. Struct. Biol 1999, 6, 937-943.
13. Dhanak, D.; Duffy, K. J.; Johnston, V. K.; Lin-Goerke, J.; Darcy, M.; Shaw, A. N.; Gu, B.; Silverman, C.; Gates, A. T.; Nonnemacher, M. R.; Earnshaw, D. L.; Casper, D. J.; Kaura, A.; Baker, A.; Greenwood, C.; Gutshall, L. L.; Maley, D.; DelVecchio, A.; Macarron, R.; Hofmann, G. A.; Alnoah, Z.; Cheng, H. Y.; Chan, G.; Khandekar, S.; Keenan, R. M.; Sarisky, R. T. Identification and biological characterization of heterocyclic inhibitors of the hepatitis C virus RNA-dependent RNA polymerase. J. Biol. Chem. 2002, 277, 38322-38327.
14. Ukrainets, I. V.; Taran, E. A.; Gorokhova, O. V.; Jaradat, N. A.; Voronina, L. N.; Porokhnyak, I. V. 4-Hydroxy-2-quinolones. Part 42. Synthesis and biological activity of 1-substituted 2-oxo-3-(2H-1,2,4-benzothiadiazine-1,1- dioxid-3-yl)-4-hydroxyquinolines. Chem. Heterocycl. Compd. (Engl. Transl.) 2000, 36, 346-350.
15. For arelated reaction employing malonate nucleophiles see: Coppola, G. M.; Damon, R. E.; Hardtmann, G. E. 4-Hydroxy-2-quinolinone-3-carboxylic Acids. Synthesis 1981 391-392.
16. Kovalenko, S. N.; Chernykh, V. P.; Shkarlat, A. E.; Ukrainets, I. V.; Gridasov, V. I.; Rudnev, S. A. Recyclization of 2-imino-2H-1-benzopyrans under the influence of nucleophilic reagents. 2. Reaction of 2-iminocoumarin-3- carboxamides with o-aminobenzenesulfonamide. Chem. Heterocycl. Compd. (Engl. Transl.) 1999, 34, 791-795.
17. Hughes, D. L. The Mitsunobu reaction. Org. React. (New York) 1992, 42, 335-656.
18. For the synthesis of a related 1,4-dihydro-2-quinazolinyl carbamate, see: Rastogi, R.; Sharma, S. Synthesis of 2-substituted quinazolines and quinazolones as potential anthelmintics. Indian J. Chem., Sect. B 1982, 21B, 744-746.
19. For the thermal condensation of isatoic anhydrides with aryl isocyanate to form quinazolinediones, see: Reddy, C. K.; Reddy, P. S. N.; Ratnam, C. V. Synthesis of 3-aryl-1H,3H-quinazolin-2,4-diones and their 2-thio analogs. Indian J. Chem., Sect. B 1987, 26B, 882-883.
20. For recent developments see: Wakita, T.; Pietschmann, T.; Kato, T.; Date, T.; Miyamoto, M.; Zhao, Z.; Murthy, K.; Habermann, A.; Krausslich, H.-G.; Mizokami, M.; Bartenschlager, R.; Liang, T. J. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat. Med. 2005, 11, 791-796.
21. Luo, G.; Cunningham, M.; Kim, S.; Burn, T.; Lin, J.; Sinz, M.; Hamilton, G.; Rizzo, C.; Jolley, S.; Gilbert, D.; Downey, A.; Mudra, D.; Graham, R.; Carrol, K.; Xie, J.; Madan, A.; Parkinson, A.; Christ, D.; Selling, B.; Lecluyse, E.; Gan, L.-S. CYP3A4 induction by drugs: Correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug Metab. Dispos. 2002, 30, 795-804.
22. Boffito, M.; Back, D. J.; Blaschke, T. F.; Rowland, M.; Bertz, R. J.; Gerber, J. G.; Miller, V. Protein binding in antiretroviral therapies. AIDS Res. Hum. Retroviruses 2003, 19, 825-835.
23. Andrisano, M. G.; Di Bella, M.; Ferrari, P.; Raffa, L.; Baggio, G. G. Heteroarylalkanoic acids with possible antiinflammatory action. II. Farmaco Ed. Sci. 1981, 36, 905-915.
24. Katsifis, A. G.; McPhee, M. E.; Mattner, F.; Ridley, D. D. Synthesis of 1231-labeled analogues of imidazobenzodiazepine receptor ligands. Aust. J. Chem. 1999, 52, 1061-1069.