Nonpeptidic HIV protease inhibitors possessing excellent antiviral activities and therapeutic indices. PD 178390: A lead HIV protease inhibitor

Bioorganic and Medicinal Chemistry

Volumn 7, Issue 12, 1999, Pages 2775-2800

  Vara Prasad, J V N ^a   Boyer, Frederick E ^a   Domagala, John M ^a   Ellsworth, Edmund L ^a   Gajda, Christopher ^a   Hamilton, Harriet W ^a   Hagen, Susan E ^a   Markoski, Larry J ^a   Steinbaugh, Bruce A ^a   Tait, Bradley D ^a   Humblet, Christine ^a   Lunney, Elizabeth A ^a   Pavlovsky, Alexander ^a   Rubin, John R ^a   Ferguson, Donna ^a   Graham, Neil ^a   Holler, Tod ^a   Hupe, Donald ^a   Nouhan, Carolyn ^a   Tummino, Peter J ^a   Urumov, A ^a   Zeikus, Eric ^a   Zeikus, Greg ^a   Gracheck, Stephen J ^a   Saunders, James M ^a   Vanderroest, Steven ^a   Brodfuehrer, Joanne ^a   Iyer, K ^a   Sinz, M ^a   Gulnik, Sergei V ^b   Erickson, John W ^b   more..

^a PFIZER INC   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Anti HIV agents; Antivirals; Aspartic protease inhibitors; HIV protease inhibitors; Nonpeptidic HIV protease inhibitors

Indexed keywords

6 [2 (4 AMINOPHENYL)ETHYL] 3 (2 TERT BUTYL 4 HYDROXY 5 METHYLPHENYLTHIO) 5,6 DIHYDRO 4 HYDROXY 6 ISOPROPYL 2 PYRANONE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; CYTOCHROME P450 3A; FUNCTIONAL GROUP; MUTANT PROTEIN; PROTEINASE INHIBITOR; UNCLASSIFIED DRUG; VIRUS ENZYME;

ANIMAL EXPERIMENT; ANTIVIRAL ACTIVITY; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; CROSS RESISTANCE; CRYSTAL STRUCTURE; CYTOTOXICITY; DRUG BIOAVAILABILITY; DRUG HALF LIFE; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PROTON NUCLEAR MAGNETIC RESONANCE; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

CELL LINE; CRYSTALLOGRAPHY, X-RAY; CYTOCHROME P-450 ENZYME SYSTEM; DISULFIDES; HIV PROTEASE; HIV PROTEASE INHIBITORS; HIV-1; HUMANS; KINETICS; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; MUTATION; PYRONES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0033391195     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0968-0896(99)00215-1     Document Type: Article

References (40)

1. Debser Z., De Clercq E. J. Immunol. Immunopharmacol. 26:1996;48.
2. Lewis J.S., Terriff C.M., Coulston D.R., Garrison M.W. Clinical Therapeutics. 19:1997;187.
3. Deeks S.G., Smith M., Holodniy M., Kahn J.O. JAMA. 277:1997;145.
4. Molla A., Granneman G.R., Sun E., Kempf D.J. Antiviral Research. 39:1998;1.
5. Mascolini M. Journal of the International Association of Physicians in AIDS Care. 4:1996;23.
6. Erickson J.W. Nature Structural Biology. 2:1995;523.
7. Van Cleef G.F., Fisher E.J., Polk R.E. Pharmacotherapy. 17:1997;774.
8. Ridky T., Leis J. J. Biol. Chem. 270:1995;29261.
9. Kuritzkes D.R. AIDS. 10:1996;S27.
10. Kempf D.J., Sham H.L. Current Pharmaceutical Design. 2:1996;225.
11. Romines K.R., Chrusciel R.A. Current Medicinal Chemistry. 2:1995;825. and references therein.
12. Vara Prasad J.V.N., Lunney E., Para K.S., Tummino P.J., Ferguson D., Hupe D., Domagala J.M., Erickson J.W. Drug Design and Discovery. 13:1996;15. and references therein.
13. Eyermann, C. J.; Jadhav, P. K.; Hodge, C. N.; Chang, C.-H.; Rodgers, J. D.; Lam, P. Y. S. In Advances in Amino Acid Mimetics and Peptidomimetics; Bell, A., Ed.; Jai Press, 1997; Vol. 1, pp 1-40.
14. Turner S.R., Strobach J.W., Tommasi R.A., Aristoff P.A., Johnshon P.A., Skulnick H.I., Dolak L.A., Seest E.P., Tomich P.K., Bohanon M.J., Horng M.-M., Lynn J.C., Chong K.-T., Hinshaw R.R., Watenpaugh K.D., Janakiraman M.N., Thaisrivongs S. J. Med. Chem. 41:1998;3467.
15. Vara Prasad J.V.N., Para K.S., Lunney E.A., Ortwine D.F., Dunbar J.B., Ferguson D., Tummino P.J., Hupe D., Tait B.D., Domagala J.M., Humblet C., Bhat T.N., Liu B., Guerin D.M.A., Baldwin E.T., Erickson J.W., Sawyer T.K. J. Am. Chem. Soc. 116:1994;6989.
16. Vara Prasad J.V.N., Lunney E.A., Ferguson D., Tummino P.J., Rubin J.R., Reyner E.L., Stewart B.H., Guttendorf R.J., Domagala J.M., Suvorov L.I., Gulnik S.V., Topol I.A., Bhat T.N., Erickson J.W. J. Am. Chem. Soc. 117:1995;11070. and references therein.
17. Tait B.D., Hagen S., Domagala J.M., Ellsworth E., Gajda C., Hamilton H., Vara Prasad J.V.N., Ferguson D., Graham N., Hupe D., Nouhan C., Tummino P.J., Humblet C., Lunney E.A., Pavlovsky A., Rubin J., Baldwin E.T., Bhat T.N., Erickson J.W., Gulnik S.V., Liu B. J. Med. Chem. 40:1997;3781. and references therein.
18. Fritzerald P.M.D. Current Opin. Struct. Biol. 1:1993;868.
19. Hagen S., Vara Prasad J.V.N., Boyer F.E., Domagala J.M., Ellsworth E.L., Gajda C., Hamilton H.W., Markoski L.J., Steinbaugh B., Tait B.D., Lunney E.A., Tummino P.J., Ferguson D., Hupe D., Nouhan C., Gracheck S.J., Saunder J.M., VanderRoest S. J. Med. Chem. 40:1997;3707.
20. Sharmeen, L. (unpublished results).
21. Vara Prasad, J. V. N.; Lunney, E. A.; Steibaugh, B. A.; Hamilton, H. W.; Tummino, P. J.; Nouhan, C.; Graham, N.; Domagala, J. M. IBC International Conference of Protease Inhibitors: San Francisco, California, 10-11 June 1996.
22. Sinisterra, J. V.; Garcia-Raso, A.; Cabello, J. A.; Marinas, M. Synthesis 1984, 502.
23. Nahm S., Weinreb S.M. Tetrahedron Lett. 22:1981;3815.
24. Vara Prasad, J. V. N.; Markoski, L. J.; Boyer, F. E.; Domagala, J. M.; Ellsworth, E.; Gajda, C.; Hagen, S. E.; Tait, B. D.; Lunney, E. A.; Tummino, P. J.; Ferguson, D.; Holler, T.; Hupe, D.; Nouhan, C.; Gracheck, S. J.; VanderRoest, S.; Saunders, J.; Iyer, K.; Sinz, M. Bioorg. Med. Chem. Lett. (in press).
25. Tummino P.J., Vara Prasad J.V.N., Ferguson D., Nouhan C., Graham N., Domagala J.M., Ellsworth E., Gajda C., Hagen S.E., Lunney E.A., Para K.S., Tait B.D., Pavlovsky A., Erickson J.W., Gracheck S., McQuade T.J., Hupe D.J. Bioorg. Med. Chem. 4:1996;1401.
26. Tummino P.J., Ferguson D., Hupe L., Hupe D. Biochem. Biophys. Res. Commun. 200:1994;1658.
27. Buckheit R.W. Jr., Hollingshead M.G., Germany Decker J., White E.L., McMahon J.B., Allen L.B., Ross L.R., Decker D., Westbrook L., Shannon W.M., Weislow O., Bader J.P., Boyd M.R. Antiviral Res. 21:1993;247.
28. Hamilton, H.; Hagen, S.; Steinbaugh, B.; Lunney, E.; Pavlovsky, A.; Domagala, J.; Tummino, P.; Ferguson, D.; Gracheck, S. XIVth International Symposium on Medicinal Chemistry: Maastricht, The Netherlands, 8-12 September 1996.
29. Thaisrivongs S., Skulnick H.I., Turner S.R., Strobach J.W., Tommasi R.A., Johnson P.D., Aristoff P.A., Judge T.M., Gammill R.B., Morris J.K., Romines K.R., Chrusciel R.A., Hinshaw R.R., Chong K.-T., Tarpley W.G., Poppe S.M., Slade D.E., Lynn J.C., Horng M.-M., Tomich P.K., Seest E.P., Dolak L.A., Howe W.J., Howard G.M., Schwende F.J., Toth L.N., Padbury G.E., Wilson K.F., Rush B.D., Ruwart M.J., Koeplinger K.A., Zhao Z., Cole S., Zaya R.M., Kakuk T.J., Janakiraman M.N., Watenpaugh K.D. J. Med. Chem. 39:1996;5349.
30. Poppe S.M., Slade D.E., Chong K.-T., Hinshaw R.R., Pagano P.J., Markowitz M., Ho D.D., Mo H., Gorman III R.R., Dueweke T.J., Thaisrivongs S., Tarpley W.G. Antimicrobial Agents and Chemotherapy. 41:1997;1058.
31. Vara Prasad J.V.N., Para K.S., Tummino P.J., Ferguson D., McQuade T.J., Lunney E.A., Rapundalo S.T., Batley B.L., Hingorani G., Domagala J.M., Gracheck S.J., Bhat T.N., Liu B., Baldwin E.T., Erickson J.W., Sawyer T.K. J. Med. Chem. 38:1995;898.
32. Vara Prasad J.V.N., Pavlovsky A., Para K.S., Ellsworth E.L., Tummino P.J., Nouhan C., Feguson D. Bioorg. Med. Chem. Lett. 6:1996;1133.
33. Rice W.G., Bader J.P. Adv. Pharmacol. 33:1995;389.
34. Domagala, J. M.; Boyer, F.; Ellsworth, E.; Gajda, C.; Hagen, S.; Hamilton, H.; Markoski, L.; Vara Prasad, J. V. N.; Steinbaugh, B.; Tait, B.; Lunney, E.; Brodfuehrer, J.; Gracheck, S.; Holler, T.; Hupe, D.; Iyer, K.; Pavlovsky, A.; Saunders, J.; Sharmeen, L.; Tummino, P. 5th Conference on Retroviruses and Opportunistic Infections: Chicago, IL, 1-5 February 1998.
35. Reich S.H., Melnick M., Davies J.F., Krzysztof A., Lewis K.K., Fuhry M.A., Pino M., Trippe A.J., Nguyem D., Dawson H., Wu B.-W., Musick L., Kosa M., Kahil D., Webber S., Gehlhaar D.K., Andrada D., Shetty B. Proc. Natl. Acad. Sci. USA. 92:1995;3298.
36. Sharmeen, L.; Heldsinger, A.; McQuade, T.; Domagala, J.; Gracheck, S. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy: Toronto, Canada, September 1997, Abstract No. I-64.
37. VanderRoest, S.; Wold, S.; Saunders, J. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy: Toronto, Canada, September 1997, Abstract No. I-84.
38. Chiba M., Hensleigh M., Nishime J.A. Drug Metab. Dispos. 24:1996;307.
39. Kumar G.N., Rodrigues A.D., Buko A.M. J. Pharmacol. Exp. Ther. 277:1996;423.
40. Rodrigues A.D. J. Pharmacol. Exp. Ther. 270:1994;414.