Potent and selective HIV-1 ribonuclease H inhibitors based on a 1-hydroxy-1,8-naphthyridin-2(1H)-one scaffold

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 22, 2010, Pages 6754-6757

  Williams, Peter D ^a   Staas, Donnette D ^a   Venkatraman, Shankar ^a   Loughran, H Marie ^a   Ruzek, Rowena D ^a   Booth, Theresa M ^a   Lyle, Terry A ^a   Wai, John S ^a   Vacca, Joseph P ^a   Feuston, Bradley P ^a   Ecto, Linda T ^a   Flynn, Jessica A ^a   Distefano, Daniel J ^a   Hazuda, Daria J ^a   Bahnck, Carolyn M ^a   Himmelberger, Amy L ^a   Dornadula, Geetha ^a   Hrin, Renee C ^a   Stillmock, Kara A ^a   Witmer, Marc V ^a   Miller, Michael D ^a   Grobler, Jay A ^a   more..

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

HIV; Reverse transcriptase; RNase H inhibitor

Indexed keywords

1 HYDROXY1,8 NAPHTHYRIDIN 2(1H) ONE; INTEGRASE; RIBONUCLEASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL ANALYSIS; CYTOTOXICITY; DRUG EFFICACY; DRUG INHIBITION; DRUG POTENCY; FEMALE; HELA CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; IC 50; NONHUMAN; REACTION OPTIMIZATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; STRUCTURE ACTIVITY RELATION; VIROGENESIS; VIRUS REPLICATION;

ANTI-HIV AGENTS; ENZYME INHIBITORS; HELA CELLS; HIV-1; HUMANS; NAPHTHYRIDINES; RIBONUCLEASE H;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 77958045051     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.08.135     Document Type: Article

References (17)

1. J.-M. Molina Drugs 68 2008 567
2. S.J. Schultz, and J.J. Champoux Virus Res. 134 2008 86
3. K. Klumpp, and T. Mirzadegan Curr. Pharm. Des. 12 2006 1909
4. M. Nowotny, and W. Yang EMBO J. 25 2006 1924
5. C.A. Shaw-Reid, V. Munshi, P. Graham, A. Wolfe, M. Witmer, R. Danzeisen, D.B. Olsen, S.S. Carroll, M. Embrey, J.S. Wai, M.D. Miller, J.L. Cole, and D.J. Hazuda J. Biol. Chem. 278 2003 2777
6. K. Klumpp, J.Q. Hang, S. Rajendran, Y. Yang, A. Derosier, P.W.K. In, H. Overton, K.E.B. Parkes, N. Cammack, and J.A. Martin Nucleic Acids Res. 31 2003 6852
7. D.M. Himmel, K.A. Maegley, T.A. Pauly, J.D. Bauman, K. Das, C. Dharia, A.D. Clark Jr., K. Kevin Ryan, M.J. Hickey, R.A. Love, S.H. Hughes, S. Bergqvist, and E. Arnold Structure 17 2009 1625
8. T.A. Kirschberg, M. Balakrishnan, N.H. Squires, T. Barnes, K.M. Brendza, X. Chen, E.J. Eisenberg, W. Jin, N. Kutty, S. Leavitt, A. Liclican, Q. Liu, X. Liu, J. Mak, J.K. Perry, M. Wang, W.J. Watkins, and E.B. Lansdon J. Med. Chem. 52 2009 5781
9. Williams, P. D.; Staas, D. D.; Venkatraman, S.; Booth, T. M.; Loughran, H. M.; Ruzek, R. D.; Wai, J. S.; Vacca, J. P.; Prasad, S.; Munshi, S. K.; Bahnck, C.; Dornadula, G.; Hrin, R. C.; Himmelberger, A. L.; Miller, M. D.; Hazuda, D. J.; Grobler, J. A. 16th Conference on Retroviruses and Opportunistic Infections, poster 559, Feb 8-11, 2009.
10. H.-P. Su, Y. Yan, S. Prasad, R.F. Smith, C.L. Daniels, Abeywickrema, J.C. Reid, H.M. Loughran, M. Kornienko, S. Sharma, J.A. Grobler, B. Xu, V. Sardana, T.J. Allison, P.D. Williams, P.L. Darke, D.J. Hazuda, and S. Munshi J. Virol. 84 2010 7625
11. J.K. Pratt, P. Donner, K.F. McDaniel, C.J. Maring, W.M. Kati, H. Mo, T. Middleton, Y. Liu, T. Ng, Q. Xie, R. Zhang, D. Montgomery, A. Molla, D.J. Kempf, and W. Kohlbrenner Bioorg. Med. Chem. Lett. 15 2005 1577
12. C.A. Shaw-Reid, B. Feuston, V. Munshi, K. Getty, J. Krueger, D.J. Hazuda, M.A. Parniak, M.D. Miller, and D. Lewis Biochemistry 44 2005 1595
13. During the course of this work it was found that RNase H inhibitors exhibited partial inhibition of DNA polymerase activity with RNA templates and not with DNA templates. The inhibition observed exclusively on RNA templates is believed to be an indirect effect due to formation of stable complexes in which inhibitor is bound to the RNase H active site. Grobler, J. A., unpublished results.
14. J.A. Grobler, K. Stillmock, B. Hu, M. Witmer, P. Felock, A.S. Espeseth, A. Wolfe, M. Egbertson, M. Bourgeois, J. Melamed, J.S. Wai, S. Young, J. Vacca, and D.J. Hazuda Proc. Natl. Acad. Sci. U.S.A. 99 2002 6661
15. D.J. Hazuda, P. Felock, M. Witmer, A. Wolfe, K. Stillmock, J.A. Grobler, A. Espeseth, L. Gabryelski, W. Schleif, C. Blau, and M.D. Miller Science 287 2000 646
16. R. Hamid, Y. Rotshteyn, L. Rabadi, R. Parikh, and P. Bullock Toxicol. In Vitro 18 2004 703
17. J.P. Vacca, B.D. Dorsey, W.A. Schleif, R.B. Levin, S.L. McDaniel, P.L. Darke, J. Zugay, J.C. Quintero, O.M. Blahy, E. Roth, V. Sardana, A.J. Schlabach, P.I. Graham, J.H. Condra, L. Gotlib, M.K. Holloway, J. Lin, I. Chen, K. Vastag, D. Ostovic, P.S. Anderson, E.A. Emini, and J.R. Huff Proc. Natl. Acad. Sci. U.S.A. 91 1994 4096