Identification of benzofurano[3,2-d]pyrimidin-2-ones, a new series of HIV-1 nucleotide-competing reverse transcriptase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 23, Issue 9, 2013, Pages 2775-2780

  Tremblay, Martin ^a   Bethell, Richard C ^a   Cordingley, Michael G ^a   Deroy, Patrick ^a   Duan, Jianmin ^a   Duplessis, Martin ^a   Edwards, Paul J ^a   Faucher, Anne Marie ^a   Halmos, Ted ^a   James, Clint A ^a   Kuhn, Cyrille ^a   Lacoste, Jean Éric ^a   Lamorte, Louie ^a   Laplante, Steven R ^a   Malenfant, Éric ^a   Minville, Joannie ^a   Morency, Louis ^a   Morin, Sébastien ^a   Rajotte, Daniel ^a   Salois, Patrick ^a   Simoneau, Bruno ^a   Tremblay, Sonia ^a   Sturino, Claudio F ^a,b   more..

^a BOEHRINGER INGELHEIM CANADA LTD   (Canada)

^b VERTEX PHARMACEUTICALS   (United States)

Author keywords

Benzofurano 3,2 d pyrimidin 2 one; HIV 1; NcRTI; Reverse transcriptase

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; BENZOFURAN DERIVATIVE; BENZOFURANO[3,2 D]PYRIMIDIN 2 ONE DERIVATIVE; PYRIMIDINONE DERIVATIVE; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; ARTICLE; CELL MEMBRANE PERMEABILITY; CONTROLLED STUDY; CROSS RESISTANCE; CYTOTOXICITY; DRUG METABOLISM; DRUG POTENCY; DRUG SOLUBILITY; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; HUMAN; IC 50; IN VITRO STUDY; LIVER MICROSOME METABOLISM; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; BENZOFURANS; HIV REVERSE TRANSCRIPTASE; HIV-1; HUMANS; MICROSOMES, LIVER; NUCLEOTIDES; PROTEIN BINDING; PYRIMIDINONES; RATS; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 84876158501     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2013.02.042     Document Type: Article

References (25)

1. For a recent UN report, see online: www.unaids.org/en/media/unaids/ contentassets/documents/epidemiology/2012/gr2012/20121120-UNAIDS-Global-Report- 2012-en.pdf (accessed January 23rd, 2013).
2. For a recent review regarding the impact of antiretroviral therapy on the HIV pandemic, see: S. Broder Antiviral Res. 85 2010 1
3. T. Cihlar, and A.S. Ray Antiviral Res. 85 2010 39
4. M.-P. de Béthune Antiviral Res. 85 2010 75
5. A. Basavapathruni, and K.S. Anderson FASEB J. 21 2007 3795
6. H.C. Castro, N.I.V. Loureiro, M. Pujol-Luz, A.M.T. Souza, M.G. Albuquerque, D.O. Santos, L.M. Cabral, I.C. Frugulhetti, and C.R. Rodrigues Curr. Med. Chem. 13 2006 313
7. L. Menendez-Arias Antiviral Res. 85 2010 210
8. R. Paredes, and B. Clotet Antiviral Res. 85 2010 245
9. T. Hawkins Antiviral Res. 85 2010 201
10. D. Jochmans, J. Deval, B. Kesteleyn, H. Van Marck, E. Bettens, I. De Baere, P. Dehertogh, T. Ivens, M. Van Ginderen, B. Van Schoubroeck, M. Ehteshami, P. Wigerinck, M. Götte, and K. Hertogs J. Virol. 80 2006 12283
11. Z. Zhang, M. Walker, W. Xu, J.H. Shim, J.-L. Girardet, R.K. Hamatake, and Z. Hong Antimicrob. Agents Chemother. 50 2006 2772
12. G. Maga, M. Radi, S. Zanoli, F. Manetti, R. Cancio, U. Hübscher, S. Spadari, C. Falciani, M. Terrazas, J. Vilarrasa, and M. Botta Angew. Chem., Int. Ed. 2007 1810 46
13. G. Maga, M. Radi, M.-A. Gerard, M. Botta, and E. Ennifar Viruses 2 2010 880
14. M. Ehteshami, B.J. Scarth, E.P. Tchesnokov, C. Dash, S.F.J. Le Grice, S. Hallenberger, J. Jochmans, and M. Götte J. Biol. Chem. 283 2008 29904
15. 6 compounds, in HTS mode, using this optimized assay format. See Supplementary data for assay details.
16. 50 is defined as the concentration of a drug resulting in the death of 50 percent of the host cells.
17. Sturino, C.; DeRoy, P.; Duplessis, M.; Edwards, P. J.; Faucher, A. -M.; Halmos, T.; James, C.; Lacoste, J. -E.; Malenfant, E.; Minville, J.; Morency, L.; Morin, S.; Tremblay, M.; Yoakim, C. PCT Int. Appl. WO 2010/115264, 2010.
18. a value was calculated using ACD/PhysChem Suite version 12, ACD Labs, Toronto.
19. P.J. Edwards, and C. Sturino Curr. Med. Chem. 18 2011 3116
20. Related SAR demonstrated that analogues containing X = Br or Cl showed similar potencies.
21. K. Palm, K. Luthman, J. Ros, J. Grasjo, and P. Artursson J. Pharmacol. Exp. Ther. 291 1999 435
22. P.A. Shore, B.B. Brodie, and C.A.M. Hogben J. Pharmacol. Exp. Ther. 119 1957 361
23. K.C. Kumar Swamy, N.N. Bhuvan Kumar, E. Balaraman, and K.V.P. Pavan Kumar Chem. Rev. 109 2009 2551
24. N. Miyaura, and A. Suzuki Chem. Rev. 95 1995 2457
25. E.B. Lansdon, D. Samuel, L. Lagpacan, K.M. Brendza, K.L. White, M. Hung, X. Liu, C.G. Boojamra, R.L. Mackman, T. Cihlar, A.S. Ray, M.E. McGrath, and S. Swaminathan J. Mol. Biol. 397 2010 967