Tricylic ureas: A new class of HIV-1 protease inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 24, 1998, Pages 3615-3620

  Han, Wei ^a   Pelletier, Jeffrey C ^a,b   Hodge, C Nicholas ^a,c  

^a DUPONT COMPANY   (United States)

^b PFIZER INC   (United States)

^c Caliper Life Sciences   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEINASE INHIBITOR; UREA DERIVATIVE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; DRUG DERIVATIVE; UREA;

ARTICLE; COMPETITIVE INHIBITION; DIASTEREOISOMER; DRUG POTENCY; HUMAN IMMUNODEFICIENCY VIRUS 1; MOLECULAR MODEL; NONHUMAN; OXIDATION; PROTEINASE INHIBITION; STRUCTURE ACTIVITY RELATION; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECT;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1;

ANTI-HIV AGENTS; HIV PROTEASE INHIBITORS; HIV-1; MOLECULAR STRUCTURE; UREA;

EID: 0032534217     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00659-3     Document Type: Article

References (27)

1. 1. (a) Weiss, R. A. Science 1993, 260, 1273 and references cited therein.
2. (b) Debouck, C. AIDS Res. Human Retroviruses 1992, 8, 153.
3. (c) Katz, R. A.; Skalka, A. M. Annu. Rev. Biochem. 1994, 63, 133.
4. 2. Kohl, N. E.; Emini, E. A.; Schleif, W. A.; Davis, L. J.; Heimbach, J. C.; Dixon, R. A. F.; Scolnick, E. M.; Sigal, I. S. Proc. Natl. Acad. Sci.. 1988, 85, 4686.
5. 3. (a) Norbeck, D. W.; Kempf, D. J. Annu. Rep. Med. Chem. 1991, 26, 141.
6. (b) Tomasselli, A. G.; Howe, W. J.; Sawyer, T. K.; Wlodawer, A.; Heinrikson, R. L. Chim. Oggi 1991, 6.
7. (c) Wlodawer, A.; Erickson, J. W. Annu. Rev. Biochem. 1993, 62, 543.
8. (d) Appelt, K. Perspect. Drug Discovery Des. 1993, 1, 23.
9. 4. (a) Lin, J. H. Adv. Drug Delivery Rev. 1997, 27, 774.
10. (b) Vacca, J. P.; Condra, J. H. Drug Discovery Today 1997, 2, 261.
11. 5. (a) 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, N.; Chang, C-H.; Weber, P. C.; Jackson, D. A.; Sharpe, T. R.; Erickson-Viitanen, S. Science 1994, 263, 380.
12. (b) Lam, P. Y. S.; Ru, Y.; Jadhav, P. K.; Aldrich, P. E.; DeLucca, G. V.; Eyermann, C. J.; Chang, C-H.; Emmett, G.; Holler, E. R.; Daneker, W. F.; Li, L.; Confalone, P. N.; McHugh, R. J.; Han, Q.; Markwalder, J. A.; Seitz, S. P.; Sharpe, T. R.; Bacheler, L. T.; Rayner, M. M.; Klabe, R. M.; Shum, L.; Winslow, D. L.; Kernhauser, D. M.; Jackson, D. A.; Erickson-Viitanen, S.; Hodge, C. N. J. Med. Chem. 1996, 39, 3514.
13. (c) Kaltenbach, R. F.; Nugiel, D. A.; Lam, P. Y. S.; Klabe, R. M.; Seitz, S. P. J. Med. Chem. submitted.
14. 6. (a) O'Connor, S. D.; Smith, P. E.; Al-Obeidi, F.; Pettitt, B. M. J. Med. Chem. 1992, 35, 2870.
15. (b) Hodge, C. N.; Straatsma, T. P.; McCammon, J. A. Structure Biology of Viruses 1997, 451.
16. 7. The synthetic methodology of compound 4 was developed in Professor Henry Rapoport's laboratory based on the joint program between DuPont-Merck and U. C. Berkeley. Campbell, J. A.; Rapoport, H. J. Org. Chem. 1996, 61, 6313.
17. 8. (a) Konradi, A. W.; Pedersen, S. F. J. Org. Chem. 1992, 57, 28.
18. (b) Konradi, A. W.; Kemp, S. J.; Pedersen, S. F. J. Am. Chem. Soc. 1994, 116, 1316.
19. (c) Kraynack, E. A.; Pedersen, S. F. J. Org. Chem. 1993, 58, 6114.
20. 9. Swindell, C. S.; Chander, M. C.; Heerding, J. M.; Klimko, P. G. J. Org. Chem. 1996, 61, 1101.
21. 10. McMurry, J. E.; Lectka, T.; Rico, J. G . J. Org. Chem. 1989, 54, 3748.
22. 11. Molander, G. A.; Harris, C. R. Chem. Rev. 1996, 96, 307.
23. 3. NOE effects were observed with the protons at 4 and 5 positions.
24. 13. (a) Rodgers, J. D.; Johnson, B. L.; Wang, H.; Greenberg, R. A.; Erickson-Viitanen, S.; Klabe, R. M.; Bacheler, L.; Cordova, B. C.; Rayner, M. M.; Lam, G. N.; Chang, C-H. Bioog. Med. Chem. Lett. 1996, 2919.
25. (b) Rodgers, J. D.; Johnson, B. L.; Wang, H.; Erickson-Viitanen, S.; Klabe, R. M.; Bacheler, L.; Cordova, B. C.; Chang, C-H. Bioog. Med. Chem. Lett. 1998, 715.
26. 13C and HRMS spectra.
27. 15. Inhibition of HIV protease was measured by assaying the cleavage of a fluorescent peptide using HPLC. Erickson-Viitanen, S.; Klabe, R. M.; Cawood, P. G.; O'Neal, P. L.; Meek, J. L. Antimicro. Agents Chemo. 1994, 38, 1628.