Discovery of novel 1-phenyl-cycloalkane carbamides as potent and selective influenza fusion inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 12, 2010, Pages 3507-3510

  Tang, Guozhi ^a   Qiu, Zongxing ^a   Lin, Xianfeng ^a   Li, Wentao ^a   Zhu, Lei ^a   Li, Shaohua ^b   Li, Haodong ^b   Wang, Lisha ^a   Chen, Li ^a   Wu, Jim Z ^a   Yang, Wengang ^a  

^a Roche RandD Center China Ltd   (China)

^b WUXI APPTEC   (China)

Author keywords

Fusion inhibitor; Hemagglutinin; Influenza A

Indexed keywords

1 PHENYL CYCLOPENTANECARBOXYLIC ACID (4 CYANOPHENYL)METHYLAMIDE; ANTIVIRUS AGENT; LY 180299; TRIPERIDENE; UNCLASSIFIED DRUG; UREA DERIVATIVE;

ANIMAL CELL; ANTIVIRAL ACTIVITY; ARTICLE; BACTERIAL STRAIN; CELL STRAIN; DRUG ACTIVITY; DRUG IDENTIFICATION; DRUG INHIBITION; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; INFLUENZA VIRUS A H1N1; NONHUMAN; PHYLOGENY;

ANIMALS; CELL LINE; CYCLOPARAFFINS; DOGS; DRUG DISCOVERY; HEMAGGLUTININ GLYCOPROTEINS, INFLUENZA VIRUS; HUMANS; INFLUENZA A VIRUS, H1N1 SUBTYPE; INFLUENZA, HUMAN; STRUCTURE-ACTIVITY RELATIONSHIP; UREA;

ORTHOMYXOVIRIDAE;

EID: 77954216897     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.04.141     Document Type: Article

References (22)

1. N.M. Bouvier, and P. Palese Vaccine 26S 2008 D49
2. World Health Organization. Available from: http://www.who.int/.
3. E. de Wit, and R.A. Fouchier J. Clin. Virol. 41 2008 1
4. G.J.D. Smith, D. Vijaykrishna, J. Bahl, S.J. Lycett, M. Worobey, O.G. Pybus, S.K. Ma, C.L. Cheung, J. Raghwani, S. Bhatt, J.S.M. Peiris, Y. Guan, and A. Rambaut Nature 459 2009 1122
5. A.S. Fauci Emerg. Infect. Dis. 12 2006 73
6. E.D. Clercq Nat. Rev. Drug Disc. 5 2006 1015
7. K. Klumpp Expert Opin. Ther. Patents 14 2004 1153
8. D.M. Weinstock, and G.J. Zuccotti Am. Med. Assoc. 301 2009 1066
9. D.S. Dimitrov Nat. Rev. Microbiol. 2 2004 109
10. M.S. Deshpande, J. Wei, G. Luo, C. Cianci, S. Danetz, A. Torri, L. Tiley, M. Krystal, K. Yu, S. Huang, Q. Gao, and N.A. Meanwell Bioorg. Med. Chem. Lett. 11 2001 2393
11. K.A. Staschke, S.D. Hatch, J.C. Tang, W.J. Hornback, J.E. Munroe, J.M. Colacino, and M.A. Muesing Virology 248 1998 264
12. M. Oka, Y. Ishiwata, N. Iwata, N. Honda, and T. Kakigami Chem. Pharm. Bull. 49 2001 379
13. J. Sui, W. Hwang, S. Perez, G. Wei, D. Aird, L. Chen, E. Santelli, B. Stec, G. Cadwell, M. Ali, H. Wan, A. Murakami, A. Yammanuru, T. Han, N.J. Cox, L.A. Bankston, R.O. Donis, R.C. Liddington, and W.A. Marasco Nat. Struct. Mol. Biol. 16 2009 265
14. D.C. Ekiert, G. Bhabha, M. Elsliger, R.H.E. Friesen, M. Jongeneelen, M. Throsby, J. Goudsmit, and I.A. Wilson Science 324 2009 246
15. Y.S. Boriskin, I.A. Leneva, E.-I. Pecheur, and S.J. Polyak Curr. Med. Chem. 15 2008 997
16. M. Stahl, H. Mauser, M. Tsui, and N.R. Taylor J. Med. Chem. 48 2005 4358
17. For detailed CPE assay conditions, see: S. Shigeta, S. Mori, J. Watanabe, S. Soeda, K. Takahashi, and T. Yamase Antimicrob. Agents Chemother. 41 1997 1423
18. S. Thoennes, N. Li, B. Lee, W.A. Langley, J.J. Skehel, R.J. Russell, and D.A. Steinhauer Virology 370 2008 403
19. Calacino, J. M.; Hatch, S. D.; Hornback, W. J.; Muesing, M. A.; Munroe, J. E.; Staschke, K. A.; Tang, J. C. PCT Int. Appl. WO9728802, 1997.
20. In a trypsin sensitivity assay, 6 μg of purified HA was incubated with compounds at 31 °C for 15 min. Then the pH of the solution was adjusted to ∼5.0 to trigger HA conformational changes. After neutralization with Tris buffer, the solution was treated with 4 μg of trypsin at 37 °C for 30 min. The extent of trypsin digestion of HA was revealed on a 10% SDS-PAGE gel that was stained with Coomassie blue G-250.
21. 1H NMR (MeOD, 400 MHz), 7.59 (d, 2H, J = 8.4 Hz), 7.32-7.22 (m, 3H), 7.12-7.06 (m, 4H), 3.08 (s, 3H), 2.44-2.37 (m, 2H), 1.98-1.96 (m, 2H), 1.77-1.62 (m, 4H).
22. R.J. Russella, P.S. Kerrya, D.J. Stevensb, D.A. Steinhauerc, S.R. Martinb, S.J. Gamblinb, and J.J. Skehelb Proc. Natl. Acad. Sci. U.S.A. 105 2008 17737