Azido-containing aryl β-diketo acid HIV-1 integrase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 6, 2003, Pages 1215-1219

  Zhang, Xuechun ^a   Pais, Godwin C G ^a   Svarovskaia, Evguenia S ^a   Marchand, Christophe ^a   Johnson, Allison A ^a   Karki, Rajeshri G ^a   Nicklaus, Marc C ^a   Pathak, Vinay K ^a   Pommier, Yves ^a   Burke, Terrence R ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; AZIDE; FUNCTIONAL GROUP; INTEGRASE INHIBITOR;

ANTIVIRAL ACTIVITY; ARTICLE; DRUG POTENCY; DRUG STRUCTURE; ENZYME INHIBITION; HUMAN IMMUNODEFICIENCY VIRUS 1; STRUCTURE ANALYSIS;

ANTI-HIV AGENTS; AZIDES; CELL LINE; CELL SURVIVAL; HIV; HIV INTEGRASE; HIV INTEGRASE INHIBITORS; HUMANS; INDICATORS AND REAGENTS; KETO ACIDS; MAGNETIC RESONANCE SPECTROSCOPY; MASS SPECTROMETRY; MODELS, MOLECULAR; MOLECULAR CONFORMATION; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 0037463757     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(03)00059-3     Document Type: Article

References (27)

1. Vittinghoff E., Scheer S., O'Malley P., Colfax G., Holmberg S.D., Buchbinder S.P. J. Infect. Dis. 179:1999;717.
2. Tozser J. Ann. N.Y. Acad. Sci. 946:2001;145.
3. Condra J.H., Miller M.D., Hazuda D.J., Emini E.A. Annu. Rev. Med. 53:2002;541.
4. Miller M.D., Hazuda D.J. Curr. Opin. Microbiol. 4:2001;535.
5. Pommier Y., Neamati N. Adv. Virus Res. 52:1999;427.
6. Pluymers W., De Clercq E., Debyser Z. Curr. Drug Targets: Infect. Disord. 1:2001;133.
7. Young S.D. Curr. Opin. Drug Disc. Dev. 4:2001;402.
8. Neamati N. Expert Opin. Ther. Pat. 12:2002;70.
9. Pommier Y., Marchand C., Neamati N. Antiviral Res. 47:2000;139.
10. Goldgur Y., Craigie R., Cohen G.H., Fujiwara T., Yoshinaga T., Fujishita T., Sugimoto H., Endo T., Murai H., Davies D.R. Proc. Natl. Acad. Sci. U.S.A. 96:1999;13040.
11. Hazuda D.J., Felock P., Witmer M., Wolfe A., Stillmock K., Grobler J.A., Espeseth A., Gabryelski L., Schleif W., Blau C., Miller M.D. Science. 287:2000;646.
12. Espeseth A.S., Felock P., Wolfe A., Witmer M., Grobler J., Anthony N., Egbertson M., Melamed J.Y., Young S., Hamill T., Cole J.L., Hazuda D.J. Proc. Natl. Acad. Sci. U.S.A. 97:2000;11244.
13. Marchand C., Zhang X., Pais G.C.G., Cowansage K., Neamati N., Burke T.R. Jr., Pommier Y. J. Biol. Chem. 277:2002;12596.
14. Vandegraaff N., Kumar R., Hocking H., Burke T.R. Jr., Mills J., Rhodes D., Burrell C.J., Li P. Antimicrob. Agents Chemother. 45:2001;2510.
15. Wai J.S., Egbertson M.S., Payne L.S., Fisher T.E., Embrey M.W., Tran L.O., Melamed J.Y., Langford H.M., Guare J.P. Jr., Zhuang L., Grey V.E., Vacc J.P., Holloway M.K., Naylor-Olsen A.M., Hazuda D.J.F.P.J., Wolfe A.L., Stillmock K.A., Schleif W.A., Gabryelski L.J., Young S.D. J. Med. Chem. 43:2000;4923.
16. Pais G.C.G., Zhang X., Marchand C., Neamati N., Cowansage K., Svarovskaia E.S., Pathak V.K., Tang Y., Nicklaus M., Pommier Y., Burke T.R. Jr. J. Med. Chem. 45:2002;3184.
17. Zhang, X.; Marchand, C.; Pommier, Y.; Burke, T. R., Jr. Abstracts of Papers, 222nd ACS National Meeting, Chicago, IL, Aug. 26-30, 2001; MEDI-102.
18. All final products provided high field H NMR and mass spectral analysis consistent with their assigned structures.
19. Schrodinger 1. Portland, OR (http://www.schrodinger. com).
20. Frisch M.J., Trucks G.W., Schlegel H.B., Scuseria G.E., Robb M.A., Cheeseman J.R., Zakrzewski V.G., Montgomery J.A. Jr., Stratmann R.E., Burant J.C., Dapprich S., Millam J.M., Daniels A.D., Kudin K.N., Strain M.C., Farkas O., Tomasi J., Barone V., Cossi M., Cammi R., Mennucci B., Pomelli C., Adamo C., Clifford S., Ochterski J., Petersson G.A., Ayala P.Y., Cui Q., Morokuma K., Salvador P., Dannenberg J.J., Malick D.K., Rabuck A.D., Raghavachari K., Foresman J.B., Cioslowski J., Ortiz J.V., Baboul A.G., Stefanov B.B., Liu G., Liashenko A., Piskorz P., Komaromi I., Gomperts R., Martin R.L., Fox D.J., Keith T., Al-Laham M.A., Peng C.Y., Nanayakkara A., Challacombe M., Gill P.M.W., Johnson B., Chen W., Wong M.W., Andres J.L., Gonzalez C., Head-Gordon M., Replogle E.S., Pople J.A. Gaussian 98, Revision A.11. 2001;Gaussian, Inc, Pittsburgh, PA.
21. This study utilized the high performance computational capabilities of the Beowulf/LoBoS3 cluster at the National Institutes of Health.
22. 20 All the minimum energy structures were confirmed by normal mode analysis, with no negative frequency found.
23. Bergman D.L., Laaksonen L., Laaksonen A. J. Mol. Graph. Modelling. 15:1997;301.
24. Laaksonen L. J. Mol. Graph. 10:1992;33.
25. 23,24 with the EP mapped onto the electron density. The isosurface value is 0.0004 with a range for the EP of 0.03 to -0.03. Reoptimization of the molecules in a solvation model (PCM) in Gaussian 98 revealed no major conformational changes nor changes of the electrostatic potential.
26. Grobler J.A., Stillmock K., Hu B., Witmer M., Felock P., Espeseth A.S., Wolfe A., Egbertson M., Bourgeois M., Melamed J., Wai J.S., Young S., Vacca J., Hazuda D.J. Proc. Natl. Acad. Sci. U.S.A. 99:2002;6661.
27. Jenkins T.M., Engleman A., Ghirlando R., Craigie R. J. Biol. Chem. 271:1996;7712.