Nonsymmetrically substituted cyclic urea HIV protease inhibitors

Journal of Medicinal Chemistry

Volumn 40, Issue 25, 1997, Pages 4079-4088

  Wilkerson, Wendell W ^a,b   Dax, Scott ^a,c   Cheatham, Walter W ^a  

^a DUPONT COMPANY   (United States)

^b Dextron Corporation   (United States)

^c R W JOHNSON PHARMACEUTICAL RES I   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MOZENAVIR; PROTEINASE INHIBITOR; UNCLASSIFIED DRUG; UREA DERIVATIVE;

ANTIVIRAL ACTIVITY; ARTICLE; CYTOTOXICITY; DRUG BIOAVAILABILITY; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; STRUCTURE ACTIVITY RELATION; VIRUS REPLICATION;

ANTI-HIV AGENTS; HIV PROTEASE INHIBITORS; RNA, VIRAL; STRUCTURE-ACTIVITY RELATIONSHIP; UREA;

EID: 0031443171     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970288b     Document Type: Article

References (20)

1. Basha, A.; Lipton, M.; Weinreb, S. M. A Mild, General Method for Conversion of Esters to Amides. Tetrahedron Lett. 1977, 4171-4174.
2. Wilkerson, W. W.; Hollis, A. Y.; Cheatham, W. W.; Lam, G. N.; Erickson-Viitanen, S.; Bacheler, L.; Cordova, B. C.; Klabe, R. M.; Meek, J. L. A Bis-[N-3-(1-Hydroxy-1-methyl-ethyl)-benzyl]-Cyclic Urea As A HIV Protease Inhibitor. Bioorg. Med. Chem. Lett. 1995, 5, 3027-3032.
3. Cheng, Y.-S. E.; Yin, F. H.; Foundling, S.; Blomstrom, D.; Kettner, C. A. Stability and Activity of Human Immunodeficiency Virus Protease: Comparison of the Natural Dimer with a Homologous, Single-chain Tethered Dimer. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 9660-9664.
4. Erickson-Viitanen, S.; Manfredi, J.; Viitanen, P.; Tribe, D. E.; Tritch, R.; Hutchison, C. A., III; Loeb, D. D.; Swanstrom, R. Cleavage of HIV-1 gag Polyprotein Synthesized In Vitro: Sequential Cleavage by Viral Protease. AIDS Res. Hum. Retroviruses 1989, 5, 577-591.
5. Bacheler, L.; Paul, M.; Otto, M. J.; Jadhav, P. K.; Stone, B. A.; Miller, J. A. An Assay for HIV RNA in Infected Cell Lysates, and Its Use for the Rapid Evaluation of Antiviral Efficacy. Antiviral Chem. Chemother. 1994, 5, 111-121.
6. Wong, Y. N.; Burcham, D. L.; Saxton, P. L.; Erickson-Viitanen, S.; Grubb, M. F.; Quon, C. Y.; Huang, S.-M. A Pharmacokinetic Evaluation of HIV Protease Inhibitors, Cyclic Ureas, in Rats and Dogs. Biopharm. Drug Dispos. 1994, 15, 535-544.
7. Grubb, M. F.; Wong, Y. N.; Burcham, D. L.; Saxton, P. L.; Quon, C. Y.; Huang, S.-M. Pharmacokinetics of HIV Protease Inhibitor DMP 323 in Rats and Dogs. Drug Met. Disp. 1994, 22, 709-712.
8. Hansch, C.; Leo, A. Exploring QSAR. Fundamentals and Applications in Chemistry and Biology; American Chemical Society: Washington, 1995.
9. Lien, E. J. In Medicinal Research; Grunewald, G. L., Ed.; Marcel Dekker: New York, 1987; Vol. 11, pp 92-102.
10. 2 = 0.990 s = 0.114
11. Wilkerson, W. W.; Hollis, A. Y.; Cheatham, W. W.; Akamike , E.; Collins, R. D.; DeLucca, I.; Jadhav, P. K.; Lam, P. Y. S.; Ru, Y. HIV Protease Inhibitory bis-Benzamides Cyclic Ureas: A QSAR Analysis. J. Med. Chem. 1996, 39, 4299-4312.
12. Lam, P. Y. S.; Jadhav, P. K.; Eyermann, C. J.; Hodge, C. N.; Ru, Y.; Bacheler, L. T.; Meek, J. L.; Otto, M. J.; Rayner, M. M.; Wong, Y. N.; Chang, C.-H.; Weber, P. C.; Jackson, D. A.; Sharp, T. R.; Erickson-Viitanen, S. Rational Design of Potent, Bioavailable, Nonpeptide Cyclic Ureas as HIV Protease Inhibitors. Science 1994, 263, 380-284.
13. Otto, M. J.; Reid, C. D.; Garber, S.; Lam, P. Y.-S.; Scarnati, H.; Bacheler, L. T.; Rayner, M. M.; Winslow, D. L. In Vitro Anti-Human Immunodeficiency Virus (HIV) Activity of XM323, A Novel HIV Protease Inhibitor. Antimicrob. Agents Chemother. 1993, 37.
14. Rayner, M. M.; Cordova, B. C.; Meade, R. P.; Aldrich, P. E.; Jadhav, P. K.; Ru, Y.; Lam, P. Y. DMP 323, A Nonpeptide Cyclic Urea Inhibitor of Human Immunodeficiency Virus (HIV) Protease, Specifically and Persistently Blocks Intracellular Processing of HIV Gag Polyprotein. Antimicrob. Agents Chemother. 1994, 38, 1635-1640.
15. Pierce, M. E.; Harris, G. D.; Islam, Q.; Radesca, L. A.; Storace, L.; Waltermire, R. E.; Wat, E.; Jadhav, P. K.; Emmett, G. C. Stereoselective Synthesis of HIV-1 Protease Inhibitor DMP 323. J. Org. Chem. 1996, 61, 444-450.
16. Kan, R. O. A Correlation of Chemical Shifts with Inductive Effect Parameters. J. Am. Chem. Soc. 1964, 86, 5180-5183.
17. a Prediction for Organic Acids and Bases; Chapman and Hall: New York, 1981.
18. Topsom, R. D. In Prog. Phys. Org. Chem.; Taft, R. W., Ed.; John Wiley & Sons: New York, 1987; Vol. 16, pp 125-191.
19. Mitchell, T. J.; Tute, M. S.; Webb, G. A. A Theoretical Study of the pKa Values of Some Clonidine-like Imidazolidines. Eur. J. Med. Chem. 1990, 25, 117.
20. as and Molecular Surface Ionization Energies for Some Azines and Azoles. J. Org. Chem. 1991, 56, 2934-2936.