HCV NS5B polymerase inhibitors 1: Synthesis and in vitro activity of 2-(1,1-dioxo-2H-[1,2,4]benzothiadiazin-3-yl)-1-hydroxynaphthalene derivatives

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 15, 2009, Pages 4476-4479

  Wang, Guangyi ^a   He, Yanzhen ^b   Sun, Jun ^b   Das, Debasis ^b   Hu, Mougang ^a   Huang, Jianhua ^a   Ruhrmund, Donald ^a   Hooi, Lisa ^a   Misialek, Shawn ^a   Ravi Rajagopalan, P T ^a   Stoycheva, Antitsa ^a   Buckman, Brad O ^a   Kossen, Karl ^a   Seiwert, Scott D ^a   Beigelman, Leonid ^a  

^a InterMune Inc   (United States)

^b WUXI APPTEC   (China)

Author keywords

Benzothiadiazine; HCV NS5B polymerase inhibitors

Indexed keywords

2 [1,1 DIOXO 2H (1,2,4) BENZOTHIADIAZIN 3 YL] 1 HYDROXYNAPHTHALENE DERIVATIVE; ANTIVIRUS AGENT; BENZOTHIADIAZINE DERIVATIVE; NONSTRUCTURAL PROTEIN 5B; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG STRUCTURE; DRUG SYNTHESIS; REPLICON;

ANIMALS; ANTIVIRAL AGENTS; BENZOTHIADIAZINES; CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN; ENZYME INHIBITORS; HEPACIVIRUS; HEPATITIS C; HUMANS; INHIBITORY CONCENTRATION 50; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, CHEMICAL; MOLECULAR STRUCTURE; NAPHTHALENES; NAPHTHOLS; STRUCTURE-ACTIVITY RELATIONSHIP; VIRAL NONSTRUCTURAL PROTEINS;

HEPATITIS C VIRUS;

EID: 67649909851     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.05.063     Document Type: Article

References (15)

1. WHO, Hepatitis C. Incidence/Epidemiology under Section Surveillance and Control. 2002. http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index.html.
2. Shepard C.W., Finelli L., and Alter M.J. Lancet Infect. Dis. 5 (2005) 558
3. Manns M., Wedemeyer H., and Cornberg M. Gut 55 (2006) 1350
4. Lindenbach B.D., and Rice C.M. Nature 436 (2005) 933
5. Beaulieu P.L. Curr. Opin. Invest. Drugs 8 (2007) 614
6. Rönn R., and Sandström A. Curr. Top. Med. Chem. 8 (2008) 533
7. Tramontano E. Mini-Rev. Med. Chem. 8 (2008) 1298
8. Tedesco R., Shaw A.N., Bambal R., Chai D., Concha N.O., Darcy M.G., Dhanak D., Fitch D.M., Gates A., Gerhardt W.G., Halegoua D.L., Han C., Hofmann G.A., Johnston V.K., Kaura A.C., Liu N., Keenan R.M., Lin-Goerke J., Sarisky R.T., Wiggall K.J., Zimmerman M.N., and Duffy K.J. J. Med. Chem. 49 (2006) 971
9. Krueger A.C., Madigan D.L., Green B.E., Hutchinson D.K., Jiang W.W., Kati W.M., Liu Y., Maring C.J., Masse S.V., McDaniel K.F., Middleton T.R., Mo H., Molla A., Montgomery D.A., Ng T.I., and Kempf D.J. Bioorg. Med. Chem. Lett. 17 (2007) 2289
10. Krueger A.C., Madigan D.L., Jiang W.W., Kati W.M., Liu D., Liu Y., Maring C.J., Masse S., McDaniel K.F., Middleton T., Mo H., Molla A., Montgomery D., Pratt J.K., Rockway T.W., Zhang R., and Kempf D.J. Bioorg. Med. Chem. Lett. 16 (2006) 3367
11. Chen C.-M., He Y., Lu L., Lim H.B., Tripathi R.L., Middleton T., Hernandez L.E., Beno D.W.A., Long M.A., Kati W.M., Bosse T.D., Larson D.P., Wagner R., Lanford R.E., Kohlbrenner W.E., Kempf D.J., Pilot-Matias T.J., and Molla A. Antimicrob. Agents Chemother. 51 (2007) 4290
12. Imai Y., Mochizuki A., and Kakimoto M. Synthesis 10 (1983) 851
13. Thanks to this manuscript reviewer's comments, the chemical synthesis of compound 21 via a different route was found in a patent application (WO2006093801, e.g., 2F), but without activity data.
14. 50 values. Z prime values under these conditions were >0.6.
15. 50 values.