Phenyl substituted 4-hydroxypyridazin-3(2 H)-ones and 5-hydroxypyrimidin-4(3 H)-ones: Inhibitors of influenza a endonuclease

Journal of Medicinal Chemistry

Volumn 57, Issue 19, 2014, Pages 8086-8098

  Sagong, Hye Yeon ^a   Bauman, Joseph D ^b   Patel, Disha ^b   Das, Kalyan ^b   Arnold, Eddy ^b   Lavoie, Edmond J ^a  

^a RUTGERS UNIVERSITY   (United States)

^b RUTGERS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 ( 2 FLUOROPHENYL) 4,5 DIMETHOXYPYRIMIDINE; 2 ( 2 FLUOROPHENYL) 5 HYDROXYPYRIMIDIN 4 (3H) ONE; 2 ( 2 FLUOROPHENYL) 5 METHOXYPYRIMIDIN 4 (3H) ONE; 2 ( 3 FLUOROPHENYL) 4,5 DIMETHOXYPYRIMIDINE; 2 ( 3 FLUOROPHENYL) 5 HYDROXYPYRIMIDIN 4 (3H) ONE; 2 ( 3 FLUOROPHENYL) 5 METHOXYPYRIMIDIN 4 (3H) ONE; 2 ( 4 FLUOROPHENYL) 4,5 DIMETHOXYPYRIMIDINE; 2 ( 4 FLUOROPHENYL) 5 HYDROXYPYRIMIDIN 4 (3H) ONE; 2 ( 4 FLUOROPHENYL) 5 METHOXYPYRIMIDIN 4 (3H) ONE; 2 CHLORO 4,5 DIMETHOXYPYRIMIDINE; 2,3 DIMETHOXYPYRAZINE; 4 ( 4 FLUOROPHENYL) 5,6 DIMETHOXYPYRIMIDINE; 4 CHLORO 5,6 DIMETHOXYPYRIMIDINE; 5 ( 4 FLUOROPHENYL) 2,3 DIMETHOXYPYRAZINE; 5 ( 4 FLUOROPHENYL) 3 HYDROXYPYRIDIN 2 (1H) ONE; 5 ( 4 FLUOROPHENYL)PYRAZIN 2,3 (1H,4H) DIONE; 5 BROMO 2,3 DIMETHOXYPYRAZINE; 5 HYDROXY 2 ( 4 FLUOROPHENYL)PYRIMIDIN 4 (3H) ONE; 6 ( 4 FLUOROPHENYL) 3 HYDROXYPYRIDIN 2 (1H) ONE; 6 ( 4 FLUOROPHENYL) 4 HYDROXYPYRIDAZIN 3 (2H) ONE; 6 ( 4 FLUOROPHENYL) 5 HYDROXYPYRIMIDIN 4 (3H) ONE; 6 ( 4 FLUOROPHENYL) 5 METHOXYPYRIMIDIN 4 (3H) ONE; ANTIVIRUS AGENT; ENDONUCLEASE; ESTERASE INHIBITOR; LIGAND; PHENYL GROUP; PYRIDAZINONE DERIVATIVE; PYRIMIDINONE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ENZYME INHIBITOR; HETEROCYCLIC COMPOUND; PYRIDAZINE DERIVATIVE; RNA DIRECTED RNA POLYMERASE;

ANIMAL CELL; ANTIVIRAL ACTIVITY; ARTICLE; CRYSTAL STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME INHIBITION; IC50; INFLUENZA VIRUS A; LIGAND BINDING; NONHUMAN; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; VIRUS STRAIN; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; ENZYMOLOGY; SYNTHESIS;

ANTIVIRAL AGENTS; AZA COMPOUNDS; ENDONUCLEASES; ENZYME INHIBITORS; INFLUENZA A VIRUS; PYRIDAZINES; RNA REPLICASE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84907886581     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500958x     Document Type: Article

References (33)

1. Hayden, F. G.; Hay, A. J. Emergence and transmission of influenza A viruses resistant to amantadine and rimantadine Curr. Top. Microbiol. Immunol. 1992, 176, 119-130
2. Bright, R. A.; Medina, M.; Xu, X.; Peresz-Oronoz, G.; Wallis, T. R.; Davis, X. M.; Provinelli, L.; Cox, N. J.; Klimov, A. I. Incidence of admantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern Lancet 2005, 366, 1175-1181
3. Moscona, A. Oseltamivir Resistance-Disabling our Influenza Defenses N. Engl. J. Med. 2005, 353, 2633-2636
4. Bloom, J. D.; Gong, L. I.; Baltimore, D. Permissive secondary mutations enable the evolution of influenza oseltamivir resistance Science 2010, 328, 1272-1275
5. Memoli, M. J.; Davis, A. S.; Proudfoot, K.; Chertow, D. S.; Hrabal, R. J.; Bristol, T.; Taubenberger, J. K. Multidrug-resistant 2009 pandemic influenza A(H1N1) viruses maintain fitness and transmissibility in ferrets J. Infect Dis. 2011, 203, 348-357
6. Das, K.; Aramini, J. M.; Ma, L.-C.; Krug, R. M.; Arnold, E. Structures of influenza A proteins and insights into antiviral drug targets Nature Struct Mol. Biol. 2010, 17, 530-538
7. He, X.; Zhou, J.; Bartlam, M.; Zhang, R.; Ma, J.; Lou, Z.; Li, X.; Li, J.; Joachimiak, A.; Zeng, Z.; Ge, R.; Rao, Z.; Liu, Y. Crystal structure of the polymerase PAC-PB1N complex from an avian influenza H5N1 virus Nature 2008, 454, 1123-1126
8. N reveals an endonuclease active site Nature 2009, 458, 909-913
9. Dias, A.; Bouvier, D.; Crépin, T.; McCarthy, A. A.; Hart, D. J.; Baudin, F.; Cusack, S.; Ruigrok, R. W. H. The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit Nature 2009, 458, 914-918
10. DuBois, R. M.; Slavish, P. J.; Baughman, B. M.; Yun, M.-K.; Bao, J.; Webby, R. J.; Webb, T. R.; White, S. W. Structural and biochemical basis for development of influenza virus inhibitors targeting the PA endonuclease PLoS Pathog. 2012, 8, e1002830
11. Kowalinski, E.; Zubieta, C.; Wolkerstorfer, A.; Szolar, O. H. J.; Ruigrok, R. W. H.; Cusack, S. Structural Analysis of Specific Metal Chelating Inhibitor Binding to the Endonuclease Domain of Influenza pH1N1 (2009) Polymerase PLoS Pathogens 2012, 8 (8) e1002831 10.1371/journal.ppat.1002831
12. Tefsen, B.; Lu, G.; Zhu, Y.; Haywood, J.; Zhao, L.; Deng, T.; Qi, J.; Gao, G. F. The N-terminal domain of PA from bat-derived influenza-like virus H17N10 has endonuclease activity J. Virol. 2013, 88, 1935-1941 10.1128/JVI.03270-13
13. Bauman, J. D.; Patel, D.; Baker, S.; Vijayan, R. S. K.; Xiang, A.; Parhi, A.; Martinez-Sobrido, L.; LaVoie, E. J.; Das, K.; Arnold, E. Crystallographic fragment screening and structure-based optimization yields a new class of influenza endonuclease inhibitors ACS Chem. Biol. 2013, 8, 2501-2508
14. Plotch, S. J.; Bouloy, M.; Ulmanen, I.; Krug, R. M. A unique Cap(m7CppXm)-dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription Cell 1981, 23, 847-858
15. 7GpppXm)-dependent endonuclease of influenza virus by 4-substituted 2,4-dioxobutanoic acid compounds Antimicrob. Agents Chemother. 1994, 38, 2827-2837
16. Hastings, J. C.; Selnick, H.; Wolanski, B.; Tomassini, J. E. Anti-influenza virus activities of 4-substituted 2,4-dioxobutanoic acid inhibitors Antimicrob. Agents Chemother. 1996, 40, 1304-1307
17. Tomassini, J.; Davies, M. E.; Hastings, J.; Lingham, R.; Mojena, M.; Raghoobar, S. L.; Singh, S. B.; Tkacz, J. S.; Goetz, M. A. A novel antiviral agent which inhibits the endonuclease of influenza viruses Antimicrob. Agents Chemother. 1996, 40, 1189-1193
18. Singh, S. B. Total synthesis of flutimide, a novel endonuclease inhibitor of influenza virus Tetrhedron Lett. 1995, 36, 2009-2012
19. Carcelli, M.; Rogolino, D.; Bacchi, A.; Rispoli, G.; Fisicaro, E.; Compari, C.; Sechi, C.; Stevaert, A.; Naesens, L. Metal-Chelating 2-Hydroxyphenyl Amide Pharmacophore for Inhibition of Influenza Virus Endonuclease Mol. Pharmaceutics 2013, 11, 304-316 10.1021/mp400482a
20. Parkes, K. E. B.; Ermert, P.; Fässler, J.; Ives, J.; Martin, J. A.; Merrett, J. H.; Obrecht, D.; Williams, G.; Klumpp, K. Use of a pharmacophore model to discover a new class of influenza endonuclease inhibitors J. Med. Chem. 2002, 46, 1153-1164
21. Chen, E.; Swift, R. V.; Alderson, N.; Feher, V. A.; Feng, G.-S.; Amaro, R. E. Computation-guided discovery of influenza endonuclease inhibitors ACS Med. Chem. Lett. 2014, 5, 61-64
22. Sagong, H. Y.; Parhi, A.; Bauman, J. D.; Patel, D.; Das, K.; Vijayan, R. S. K.; Arnold, E.; LaVoie, E. J. 3-Hydroxyquinolin(1 H)-2-ones: potential inhibitors of influenza A endonuclease ACS Med. Chem. Lett. 2013, 4, 547-550
23. Parhi, A.; Xiang, A.; Bauman, J. D.; Patel, D.; Das, K.; Vijayan, R. S. K.; Arnold, E.; LaVoie, E. J. Phenyl substituted 3-hydroxypyridin-2(1 H)-ones: potential inhibitors of influenza A endonuclease Bioorg. Med. Chem. 2013, 21, 6435-6446
24. Aronov, A.; Bandarage, U. K.; Cottrell, K.; Davies, R.; Krueger, E.; Ledeboer, M.; Ledford, B.; Le Tiran, A.; Liao, Y.; Messersmith, D.; Wang, T.; Xu, J. Tetrahydrothiazolopyridine Inhibitors of Phosphatidylinositol 3-kinase. (Vertex Pharmaceuticals, Inc.) Patent WO/2010/096389, 2010.
25. Fray, M. J.; Bull, D. J.; Carr, C. L.; Gautier, E. C. L.; Mowbray, C. E.; Stobie, A. Structure-Activity Relationships of 1,4-dihydro-(1 H,4 H)-quinoxalin-2,3-diones as N -methyl- d -aspartate (glycine site) receptor antagonists. 1. Heterocyclic substituted 5-alkyl derivatives J. Med. Chem. 2001, 44, 1951-1962
26. Darout, E.; Robinson, R. P.; McClure, K. F.; Corbett, M.; Li, B.; Shavnya, A.; Andrews, M. P.; Jones, C. S.; Li, Q.; Minich, M. L.; Mascitti, V.; Guimaraes, C. R. W.; Munchhof, M. J.; Bahnck, K. B.; Cai, C.; Price, D. A.; Liras, S.; Bonin, P. D.; Cornelius, P.; Wang, R.; Bagdasarian, V.; Sobota, C. P.; Hornby, S.; Masterson, V. M.; Joseph, R. M.; Kalgutkar, A. S.; Chen, Y. Design and synthesis of diazatricyclodecane agonists of the G-protein-coupled receptor 119 J. Med. Chem. 2013, 56, 301-319
27. Wolkenberg, S.; Harrison, S. T.; Barrow, J. C.; Zhao, Z.; Kett, N.; Zartman, A. Inhibitors of Catechol O -methyl Transferase and their Use in the Treatment of Psychotic disorders. (Merck Sharp & Dohme Corp.) Patent WO/2011/109267, 2011.
28. Guerrero, M.; Urbano, M.; Schaeffer, M.-T.; Brown, S.; Rosen, H.; Roberts, E. SAR analysis of novel non-peptide NPBWR1 (GPR7) antagonists Bioorg. Med. Chem. Lett. 2013, 23, 614-619
29. Nagashima, H.; Ukai, K.; Oda, H.; Masaki, Y.; Kaji, K. Studies on syntheses and reactions of methoxypyridazines. II. Methoxylation of 3,4,6-trichloropyridazine Chem. Pharm. Bull. 1987, 35, 350-356
30. Hondo, T.; Warizaya, M.; Niimi, T.; Namatame, I.; Yamaguchi, T.; Nakanishi, K.; Hamajima, T.; Harada, K.; Sakashita, H.; Matsumoto, Y.; Orita, M.; Takeuchi, M. 4-Hydroxypyridazin-3(2 H)-one derivatives as novel d -amino acid oxidase inhibitors J. Med. Chem. 2013, 56, 3582-3592
31. Duplantier, A. J.; Becker, S. L.; Bohanon, M. J.; Bozilleri, K. A.; Chrunyk, B. A.; Downs, J. T.; Hu, L.-Y.; El-Kattan, A.; James, L. C.; Liou, S.; Lu, J.; Maklad, N.; Mansour, M. N.; Mente, S.; Piotrowski, M. A.; Sakaya, S. M.; Sheehan, S.; Steyn; Strick, S. J.; Williams, V. A.; Zhang, Z. Discovery, SAR, and pharmacokinetics of a novel 3-hydroxyquinolin-2(1 H)-one series of potent d -amino acid oxidase (DAAO) inhibitors J. Med. Chem. 2009, 52, 3576-3585
32. Otwinowski, Z.; Minor, W. Processing of X-ray Diffraction Data Collected in Oscillation Mode. In Methods in Enzymology, 276; Carter, C. W. J.; Sweet, R. M., Eds.; Academic Press: New York, 1997; Vol. 276, pp 307-326.
33. Adams, P. D.; Afonine, P. V.; Bunkoczi, G.; Chen, V. B.; Davis, I. W.; Echols, N.; Headd, J. J.; Hung, L. W.; Kapral, G. J.; Grosse-Kunstleve, R. W.; McCoy, A. J.; Moriarty, N. W.; Oeffner, R.; Read, R. J.; Richardson, D. C.; Richardson, J. S.; Terwilliger, T. C.; Zwart, P. H. PHENIX: a comprehensive Python-based system for macromolecular structure solution Acta Crystallogr., Sect. D: Biol. Crystallogr. 2010, 66, 213-221