Novel 2-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,3,4-oxadiazole and 3-phenyl-5-[(E)-2-(thiophen-2-yl)ethenyl]-1,2,4-oxadiazole derivatives as dengue virus inhibitors targeting NS5 polymerase

European Journal of Medicinal Chemistry

Volumn 109, Issue , 2016, Pages 146-156

  Benmansour, Fatiha ^a,b,d   Eydoux, Cécilia ^a,b   Querat, Gilles ^c   De Lamballerie, Xavier ^c   Canard, Bruno ^a,b   Alvarez, Karine ^a,b   Guillemot, Jean Claude ^a,b   Barral, Karine ^a,b,d  

^a AIX MARSEILLE UNIVERSITY   (France)

^b Centre National de la Recherche Scientifique   (France)

^c Aix Marseille University IRD 190 Inserm 1207   (France)

^d AIX MARSEILLE UNIVERSITY   (France)

Author keywords

2 phenyl 5 (E) 2 (thiophen 2 yl)ethenyl 1,3,4 oxadiazole; 3 phenyl 5 (E) 2 (thiophen 2 yl)ethenyl 1,2,4 oxadiazole; Antiviral activity; Dengue virus; NS5 RdRp inhibitors

Indexed keywords

1,2,4 OXADIAZOLE DERIVATIVE; 2 (3 BROMOPHENYL) 5 [(E) 2 (5 BROMOTHIOPHEN 2 YL)ETHENYL] 1,3,4 OXADIAZOLE; 2 (3 BROMOPHENYL) 5 [(E) 2 (5 PHENYLTHIOPHEN 2 YL)ETHENYL] 1,3,4 OXADIAZOLE; 2 (3 CHLOROPHENYL) 5 [(E) 2 (5 PHENYLTHIOPHEN 2 YL)ETHENYL] 5 (3 CHLOROPHENYL) 1,3,4 OXADIAZOLE; 2 (3,4 DICHLOROPHENYL) 5 [(E) 2 (5 PHENYLTHIOPHEN 2 YL)ETHENYL] 1,3,4 OXADIAZOLE; 2 (4 BROMOPHENYL) 5 [(E) 2 (5 BROMOTHIOPHEN 2 YL)ETHENYL] 1,3,4 OXADIAZOLE; 2 (4 FLUOROPHENYL) 5 [(E) 2 (5 PHENYLTHIOPHEN 2 YL)ETHENYL] 1,3,4 OXADIAZOLE; 2 (4 METHOXYPHENYL) 5 [(E) 2 (5 PHENYLTHIOPHEN 2 YL)ETHENYL] 1,3,4 OXADIAZOLE; 2 (4 N,N DIMETHYLPHENYL) 5 [(E) 2 (5 PHENYLTHIOPHEN 2 YL)ETHENYL] 1,3,4 OXADIAZOLE; 2 [(E) 2 (5 BROMOTHIOPHEN 2 YL)ETHENYL] 5 (3 CHLOROPHENYL) 1,3,4 OXADIAZOLE; 2 [(E) 2 (5 BROMOTHIOPHEN 2 YL)ETHENYL] 5 (3 DICHLOROPHENYL) 1,3,4 OXADIAZOLE; 2 [(E) 2 (5 BROMOTHIOPHEN 2 YL)ETHENYL] 5 (3 FLUOROPHENYL) 1,3,4 OXADIAZOLE; 2 [(E) 2 (5 BROMOTHIOPHEN 2 YL)ETHENYL] 5 (4 CHLOROPHENYL) 1,3,4 OXADIAZOLE; 2 [(E) 2 (5 BROMOTHIOPHEN 2 YL)ETHENYL] 5 (4 FLUOROPHENYL) 1,3,4 OXADIAZOLE; 2 [(E) 2 (5 BROMOTHIOPHEN 2 YL)ETHENYL] 5 (4 METHOXYPHENYL) 1,3,4 OXADIAZOLE; 2 [(E) 2 (5 BROMOTHIOPHEN 2 YL)ETHENYL] 5 PHENYL 1,3,4 OXADIAZOLE; 2 [(E) 2 (5 BROMOTHIOPHEN 2 YL)ETHENYL] 5 [4 (TRIFLUOROMETHYL)PHENYL] 1,3,4 OXADIAZOLE; 2 [(E) 2 (5 PHENYLTHIOPHEN 2 YL)ETHENYL] 5 (4 TRIFLUOROMETHYLPHENYL] 1,3,4 OXADIAZOLE; 2 [(E) 2 (5 PHENYLTHIOPHEN 2 YL)ETHENYL] 5 PHENYL 1,3,4 OXADIAZOLE; 2 [(E) 2 (5 PHENYLTHIOPHEN 2 YL)ETHENYL] 5 [(4 N,N DIMETHYL)PHENYL] 1,3,4 OXADIAZOLE; 3 (5 BROMO 2 THIENYL)ACRYLIC ACID; 3 (5 PHENYL 2 THIENYL)ACRYLIC ACID; 3 CHLORO N' [(2E) 3 (5 PHENYLTHIOPHENE 2 YL)PROP 2 ENOYL] 3 CHLOROBENZOHYDRAZIDE; ANTIVIRUS AGENT; BENZENE DERIVATIVE; HINOKIFLAVONE; N' [(2E) 3 (5 BROMOTHIOPHENE 2 YL)PROP 2 ENOYL] 3 CHLOROBENZOHYDRAZIDE; NONSTRUCTURAL PROTEIN 5; THIOPHENE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; 1,3,4-OXADIAZOLE; OXADIAZOLE DERIVATIVE; RNA DIRECTED RNA POLYMERASE; VIRAL PROTEIN;

ANTIVIRAL ACTIVITY; ARTICLE; BINDING SITE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DENGUE VIRUS; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; IN VITRO STUDY; NONHUMAN; VIRUS INHIBITION; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL LINE; CHEMISTRY; DENGUE; DRUG EFFECTS; ENZYMOLOGY; HUMAN; METABOLISM; VIROLOGY;

ANIMALS; ANTIVIRAL AGENTS; CELL LINE; DENGUE; DENGUE VIRUS; HUMANS; OXADIAZOLES; RNA REPLICASE; THIOPHENES; VIRAL NONSTRUCTURAL PROTEINS;

EID: 84954060996     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2015.12.046     Document Type: Article

References (34)

1. J.S. Mackenzie, D.J. Gubler, L.R. Petersen, Emerging flaviviruses: The spread and resurgence of Japanese encephalitis, West Nile and dengue viruses, Nat. Med. 10 (2004) S98eS109.
2. D.V. Clark, M.P. Mammen Jr., A. Nisalak, V. Puthimethee, T.P. Endy, Economic impact of dengue fever/dengue hemorrhagic fever in Thailand at the family and population levels, Am. J. Trop. Med. Hyg. 72 (2005) 786-791.
3. J. Blok, Genetic relationships of the dengue virus serotypes, J. Gen. Virol. 66 (1985) 1323-1325.
4. D.J. Gubler, Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century, Trends Microbiol. 10 (2002) 100-103.
5. S.J. Thomas, T.P. Endy, Current issues in dengue vaccination, Curr. Opin. Infect. Dis. 26 (2013) 429-434.
6. M. Bollati, K. Alvarez, R. Assenberg, C. Baronti, B. Canard, S. Cook, B. Coutard, E. Decroly, X. de Lamballerie, E.A. Gould, G. Grard, J.M. Grimes, R. Hilgenfeld, A.M. Jansson, H. Malet, E.J. Mancini, E. Mastrangelo, A. Mattevi, M. Milani, G. Moureau, J. Neyts, R.J. Owens, J. Ren, B. Selisko, S. Speroni, H. Steuber, D.I. Stuart, T. Unge, M. Bolognesi, Structure and functionality in flavivirus NSproteins: Perspectives for drug design, Antivir. Res. 87 (2010) 125-148.
7. T.J. Chambers, C.S. Hahn, R. Galler, C.M. Rice, Flavivirus genome organization, expression, and replication, Annu. Rev. Microbiol. 44 (1990) 649-688.
8. A.A. Khromykh, M.T. Kenney, E.G. Westaway, trans-Complementation of flavivirus RNA polymerase gene NS5 by using Kunjin virus replicon-expressing BHK cells, J. Virol. 72 (1998) 7270-7279.
9. S.M. Rawlinson, M.J. Pryor, P.J. Wright, D.A. Jans, CRM1-mediated nuclear export of dengue virus RNA polymerase NS5 modulates interleukin-8 induction and virus production, J. Biol. Chem. 284 (2009) 15589-15597.
10. S.P. Lim, Q.Y. Wang, C.G. Noble, Y.L. Chen, H. Dong, B. Zou, F. Yokokawa, S. Nilar, P. Smith, D. Beer, J. Lescar, P.Y. Shi, Ten years of dengue drug discovery: Progress and prospects, Antivir. Res. 100 (2013) 500-519.
11. K. Alvarez, K. Barral, B. Canard, J.-C. Guillemot, X. de Lamballerie, F. Mahuteau, C. Poinsard, G. Querat, Flavivirus inhibitors and their use, PCT/EP2015/080354 (17/12/2015).
12. G.A. Patini, E.J. LaVoie, Bioisosterism: A rational approach in drug design, Chem. Rev. 96 (1996) 3147-3176.
13. P.H. Olesen, The use of bioisosteric groups in lead optimization, Curr. Opin. Drug Discov. Dev. 4 (2001) 471-478.
14. Z. Jakopin, M.S. Dolenc, Recent advances in the synthesis of 1,2,4-and 1,3,4-oxadiazoles, Curr. Org. Chem. 12 (2008) 850-898.
15. J.K. Augustine, V. Vairaperumal, S. Narasimhan, P. Alagarsamy, A. Radhakrishnan, Propylphosphonic anhydride (T3P (R)): An efficient reagent for the one-pot synthesis of 1,2,4-oxadiazoles, 1,3,4-oxadiazoles, and 1,3,4-thiadiazoles, Tetrahedron 65 (2009) 9989-9996.
16. A. Mitsch, M. Altenkamper, I. Sattler, M. Schlitzer, Non-thiol farnesyltransferase inhibitors: Utilization of the far aryl binding site by arylthienylacryloyl-aminobenzophenones, Arch. Pharm. 338 (2005) 9-17.
17. S. Borg, R.C. Vollinga, M. Labarre, K. Payza, L. Terenius, K. Luthman, Design, synthesis, and evaluation of Phe-Gly mimetics: Heterocyclic building blocks for pseudopeptides, J. Med. Chem. 42 (1999) 4331-4342.
18. A.S.S. Hamad, A.I. Hashem, Novel synthesis of N-{6-aryl-4-[(E)-2-furylmethylene]-1,2,3,4-tetrahydro-3-oxopyridazin-1-ylcarbonyl}-p-toluenesulfonamides and N-{5-[(E)-1-aroylmethyl-2-(2-furyl) vinyl]-1,3,4-oxadiazol-2-yl}-p-toluenesulfonamides, J. Heterocycl. Chem. 39 (2002) 1325-1328.
19. Y.X. Da, Z. Yang, Z.J. Quan, Z. Zhang, X.C. Wang, Utilization of 2-Benzo[b]furan carboxylic acid hydrazide in the synthesis of 1,3,4-oxadiazole derivatives, J. Heterocycl. Chem. 46 (2009) 737-741.
20. V. Padmavathi, G.S. Reddy, A. Padmaja, P. Kondaiah, Ali-Shazia, Synthesis, antimicrobial and cytotoxic activities of 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles, Eur. J. Med. Chem. 44 (2009) 2106-2112.
21. C.O. Kappe, High-speed combinatorial synthesis utilizing microwave irradiation, Curr. Opin. Chem. Biol. 6 (2002) 314-320.
22. V. Santagada, E. Perissutti, G. Caliendo, The application of microwave irradiation as new convenient synthetic procedure in drug discovery, Curr. Med. Chem. 9 (2002) 1251-1283.
23. C.O. Kappe, Controlled microwave heating in modern organic synthesis, Angew. Chem. Int. Ed. 43 (2004) 6250-6284.
24. Y. Wang, R.L. Miller, D.R. Sauer, S.W. Djuric, Rapid and efficient synthesis of 1,2,4-oxadiazoles utilizing polymer-supported reagents under microwave heating, Org. Lett. 7 (2005) 925-928.
25. T.L. Deegan, T.J. Nitz, D. Cebzanov, D.E. Pufko, J.A. Porco, Parallel synthesis of 1,2,4-oxadiazoles using CDI activation, Bioorg. Med. Chem. Lett. 9 (1999) 209-212.
26. R.F. Poulain, A.L. Tartar, B.P. Deprez, Parallel synthesis of 1,2,4-oxadiazoles from carboxylic acids using an improved, uronium-based, activation, Tetrahedron Lett. 42 (2001) 1495-1498.
27. S. Borg, G. Estennebouhtou, K. Luthman, I. Csoregh, W. Hesselink, U. Hacksell, Synthesis of 1,2,4-oxadiazole-derived, 1,3,4-oxadiazole-derived, and 1,2,4-triazole-derived dipeptidomimetics, J. Org. Chem. 60 (1995) 3112-3120.
28. J.L. Buchanan, C.B. Vu, T.J. Merry, E.G. Corpuz, S.G. Pradeepan, U.N. Mani, M. Yang, H.R. Plake, V.M. Varkhedkar, B.A. Lynch, I.A. MacNeil, K.A. Loiacono, C.L. Tiong, D.A. Holt, Structure-activity relationships of a novel class of Src SH2 inhibitors, Bioorg. Med. Chem. Lett. 9 (1999) 2359-2364.
29. A.R. Gangloff, J. Litvak, E.J. Shelton, D. Sperandio, V.R. Wang, K.D. Rice, Synthesis of 3,5-disubstituted-1,2,4-oxadiazoles using tetrabutylammonium fluoride as a mild and efficient catalyst, Tetrahedron Lett. 42 (2001) 1441-1443.
30. K.D. Rice, J.M. Nuss, An improved synthesis of 1,2,4-oxadiazoles on solid support, Bioorg. Med. Chem. Lett. 11 (2001) 753-755.
31. P. Coulerie, C. Eydoux, E. Hnawia, L. Stuhl, A. Maciuk, N. Lebouvier, B. Canard, B. Figadere, J.C. Guillemot, M. Nour, Biflavonoids of dacrydium balansae with potent inhibitory activity on dengue 2 NS5 polymerase, Planta Med. 78 (2012) 672-677.
32. Z. Yin, Y.L. Chen, W. Schul, Q.Y. Wang, F. Gu, J. Duraiswamy, R.R. Kondreddi, P. Niyomrattanakit, S.B. Lakshminarayana, A. Goh, H.Y. Xu, W. Liu, B. Liu, J.Y. Lim, C.Y. Ng, M. Qing, C.C. Lim, A. Yip, G. Wang, W.L. Chan, H.P. Tan, K. Lin, B. Zhang, G. Zou, K.A. Bernard, C. Garrett, K. Beltz, M. Dong, M. Weaver, H. He, A. Pichota, V. Dartois, T.H. Keller, P.Y. Shi, An adenosine nucleoside inhibitor of dengue virus, Proc. Nat. Acad. Sci. U. S. A. 106 (2009) 20435-20439.
33. T.L. Yap, T. Xu, Y.L. Chen, H. Malet, M.P. Egloff, B. Canard, S.G. Vasudevan, J. Lescar, Crystal structure of the dengue virus RNA-dependent RNA polymerase catalytic domain at 1.85-Angstrom resolution, J. Virol. 81 (2007) 4753-4765.
34. C.G. Noble, S.P. Lim, Y.L. Chen, C.W. Liew, L. Yap, J. Lescar, P.Y. Shi, Conformational flexibility of the dengue virus RNA-dependent RNA polymerase revealed by a complex with an inhibitor, J. Virol. 87 (2013) 5291e5295.