PNU-140690 Antiviral for AIDS HIV-1 protease inhibitor

Drugs of the Future

Volumn 23, Issue 2, 1998, Pages 146-151

  Wroblewski, T ^a   Graul, A ^a   Castaner J ^a  

^a PROUS SCIENCE   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; DELAVIRDINE; INDINAVIR; KYNOSTATIN 272; NELFINAVIR; PROTEINASE INHIBITOR; RITONAVIR; SAQUINAVIR; TIPRANAVIR; UNCLASSIFIED DRUG; ZIDOVUDINE;

ABDOMINAL CRAMP; ABDOMINAL DISCOMFORT; ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANTIVIRAL ACTIVITY; CLINICAL TRIAL; DIARRHEA; DRUG POTENTIATION; DRUG SYNTHESIS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INTRAVENOUS DRUG ADMINISTRATION; NAUSEA; NONHUMAN; ORAL DRUG ADMINISTRATION; REVIEW; VERTIGO;

EID: 0031953835     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.1998.023.02.445832     Document Type: Review

References (27)

1. Romines, K.R., Bundy, G.L., Schwartz, T.M. et al. (The Upjohn Co.). Pyranone cpds. useful to treat retroviral infections. EP 758327, JP 97512821, WO 9530670.
2. Judge, T.M., Phillips, G., Morris, J.K. et al. Asymmetric syntheses and absolute stereochemistry of 5,6-dihydro-α-pyrones, a new class of potent HIV protease inhibitors. J Amer Chem Soc 1997, 119: 3627-8.
3. Blundell, T.L., Lapatto, R., Wilderspin, A.F., Hemmings, A.M., Hobart, P.M., Danley, D.E., Whittle, P.J. The 3-D structure of HIV-1 protease and the design of antiviral agents for the treatment of AIDS. Trends Biol Sci 1990, 15: 425-30.
4. Debouck, C., Metcalf, B.W. Human immunodeficiency virus protease: A target for AIDS therapy. Drug Dev Res 1990, 21: 1-17.
5. Huff, J.R. HIV protease: A novel chemotherapeutic target for AIDS. J Med Chem 1991, 34: 2305-14.
6. Meek, T.D. Inhibitors of HIV-1 protease. J Enzyme Inhib 1992, 6: 65-98.
7. Thaisrivongs, S. Chapter 14. HIV protease inhibitors. Annu Rep Med Chem 1994, 29: 133-44.
8. Chong, K.T. Recent advances in HIV-1 protease inhibitors. Exp Opin Invest Drugs 1996, 5: 115-24.
9. Plattner, J.J., Norbeck, D.W. Obstacles to drug development from peptide leads. In: Drug Discovery Technologies, Chapter 5, C.R. Clark and W.H. Moos (Eds.), Ellis Norwood Ltd., Chichester, 1990, 92-126.
10. Thaisrivongs, S., Tomich, P.K., Watenpaugh, K.D. et al. Structure-based design of HIV protease inhibitors: 4-Hydroxycoumarins and 4-hydroxy-2-pyrones as non-peptidic inhibitors. J Med Chem 1994, 37: 3200-4.
11. Skulnick, H.I., Johnson, P.D., Howe, W.J. et al. Structure-based design of sulfonamide substituted non-peptidic HIV protease inhibitors. J Med Chem 1995, 38: 4968-71.
12. Hamilton, H.W., Tait, B.D., Gajda, C., Hagen, S.E., Ferguson, D., Lunney, E.A., Pavlovsky, A., Tummino, P.J. 6-Phenyl-6-alkylamido-5,6-dihydro-2H-pyran-2-ones: Novel HIV protease inhibitors. Bioorg Med Chem 1996, 6: 719-24.
13. Thaisrivongs, S., Skulnick, H.I., Turner, S.R. et al. Structure-based design of HIV protease inhibitors: Sulfonamide-containing 5,6-dihydro-4-hydroxy-2-pyrones as non-peptidic inhibitors. J Med Chem 1996, 39: 4349-53.
14. Johnson, P.D., Skulnick, H.I., Aristoff, P.A. et al. Structure-based design, synthesis, and SAR of dihydropyrone sulfonamides as non-peptidic HIV protease inhibitors. 36th Intersci Conf Antimicrob Agents Chemother (Sept 15-18, New Orleans) 1996, Abst 14.
15. Poppe, S.M., Slade, D.E., Chong, K.-T. et al. Antiviral activity of dihydropyrone PNU-140690, a new nonpeptidic human immunodeficiency virus protease inhibitor. Antimicrob Agents Chemother 1997, 41: 1058-63.
16. Chong, K.-T., Pagano, P.J. In vitro combination of PNU-140690, a human immunodeficiency virus type 1 protease inhibitor, with ritonavir against ritonavir-sensitive and -resistant clinical isolates. Antimicrob Agents Chemother 1997, 41: 2367-73.
17. Chong, K.T., Pagano, P.J. In vitro combination of HIV-1 protease inhibitor PNU-140690 with ritonavir against ritonavir sensitive and resistant clinical isolates. 37th Intersci Conf Antimicrob Agents Chemother (Sept 28-Oct 1, Toronto) 1997, Abst 1-197.
18. Borin, M.T., Wang, Y., Schneck, D.W., Li, H., Brewer, J.E., Daenzer, C.L. Multiple-dose, safety, tolerance, and pharmacokinetics of the protease inhibitor PNU-140690 in healthy volunteers. 5th Conf Retroviruses Opportunistic Infect (Feb 1-5, Chicago) 1998, Abst 648.
19. Baldwin, J.R., Borin, M.T., Wang, Y., Schneck, D.W., Hopkins, N.K. Effects of food and antacid on bioavailability of the protease inhibitor PNU-140690 in healthy volunteers. 5th Conf Retroviruses Opportunistic Infect (Feb 1-5, Chicago) 1998, Abst 649.
20. PNU-140690 development status. Pharmacia & Upjohn Company Communication 1998, January 22.
21. Chrusciel, R.A., Romines, K.R., Morris, J.K. et al. An efficient asymmetric synthesis of dihydropyrone HIV protease inhibitors. 11th Int Conf AIDS (July 7-12, Vancouver) 1996, Abst Mo.A.1085.
22. Seest, E.P., Dolak, L., Castle, T. The role of chiral chromatography in the discovery of a non-peptidic, HIV protease inhibitor development candidate. 11th Int Conf AIDS (July 7-12, Vancouver) 1996, Abst Mo.A.1088.
23. Janakiraman, M.N., Watenpaugh, K.D., Tomich, P.K., Chong, K.-T., Thaisrivongs, S., Strohbach, J.W. Nonpeptidic HIV protease inhibitors: Structure-based drug design of bis-sulfonamide dihydropyrones. 212th ACS Natl Meet (Aug 25-29, Orlando) 1996, Abst MEDI 207.
24. Vander Velde, S.L., Judge, T.M., Lovasz, K.D., Morris, J.K., Romines, K.R., Han, F., Gammill, R.B. Highly selective aldol reactions between a β-ketoimide and an acetylenic ketone in the asymmetric synthesis of non-peptidic HIV protease inhibitors. 213th ACS Natl Meet (April 13-17, San Francisco) 1997, Abst ORGN 608.
25. Chong, K.T., Pagano, P.J., Hinshaw, R.R. et al. Orally bioavailable dihydropyrone derivatives as potent non-peptidic protease inhibitors of human immunodeficiency virus type 1. 36th Intersci Conf Antimicrob Agents Chemother (Sept 15-18, New Orleans) 1996, Abst I157.
26. Thaisrivongs, S., Aristoff, P.A., Tarpley, W.G. et al. The dihydropyrones: Third-generation, non-peptidic HIV protease inhibitor development candidates. 11th Int Conf AIDS (July 7-12, Vancouver) 1996, Abst Tu.A.261.
27. Schwende, F.J., Howard, G.M., Wilkinson, K.F., Wilson, G.J., Rush, B.D., Chong, K.T., Zipp, G.L., Possert, P.L., Shiou, L. The pharmacokinetics and oral bioavailability of three dihydropyrone non-peptidic HIV protease inhibitors in rats and dogs. 11th Int Cong AIDS (July 7-12, Vancouver) 1996, Abst Mo.A.1087.