Synthesis and pharmacological evaluation of sulfone substituted HIV protease inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 4, 1997, Pages 399-402

  Schwartz, Theresa M ^a   Bundy, Gordon L ^a   Strohbach, Joseph W ^a   Thaisrivongs, Suvit ^a   Johnson, Paul D ^a   Skulnick, Harvey I ^a   Tomich, Paul K ^a   Lynn, Janet C ^a   Chong, Kong Teck ^a   Hinshaw, Roger R ^a   Raub, Thomas J ^a   Padbury, Guy E ^a   Toth, Lisa N ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEINASE INHIBITOR; SULFONE DERIVATIVE;

ANTIVIRAL ACTIVITY; ARTICLE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; IN VITRO STUDY;

EID: 0031576835     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00031-0     Document Type: Article

References (13)

1. 1. Romines, K. R.; Chrusciel, R. A. Curr. Med. Chem. 1995, 2, 825.
2. 2. Skulnick, H. I.; Johnson, P. D.; Howe, W. J.; Tomich, P. K.; Chong, K.-T.; Watenpaugh, K. D.; Janakiraman, M. N.; Dolak, L. A.; McGrath, J. P.; Lynn, J. C.; Horng, M.-M.; Hinshaw, R. R.; Zipp, G. L.; Ruwart, M. J.; Schwende, F. J.; Zhong, W.-Z.; Padbury, G. E.; Dalga, R. J.; Shiou, L.; Possert, P. L.; Rush, B. D.; Wilkinson, K. F.; Howard, G. M.; Toth, L. N.; Williams, M. G.; Kakuk, T. J.; Cole, S. L.; Zaya, R. M.; Lovasz, K. D.; Morris, J. K.; Romines, K. R.; Thaisrivongs, S.; Aristoff, P. A. J. Med. Chem. 1995, 38, 4968.
3. 3. Nogami, H.; Hanano, M.; Yamada, H. Chem. Pharm. Bull. 1968, 16, 580.
4. 4. Thaisrivongs, S.; Janakiraman, M. N.; Chong, K.-T.; Tomich, P. K.; Dolak, L. A.; Turner, S. R.; Strohbach, J. W.; Lynn, J. C.; Horng, M.-M.; Hinshaw, R. R.; Watenpaugh, K. D. J. Med. Chem. 1996, 39, 2400.
5. 5. Skulnick, H. I.; Johnson, P. D.; Aristoff, P. A.; Morris, J. K.; Lovasz, K. D.; Howe, W. J.; Watenpaugh, K.D.; Janakiraman, M.N.; Anderson, D.J.; Reischer, R.J.; Bundy, G.L.; Schwartz, T. M.; Banitt, L. S.; Tomich, P. K.; Lynn, J. C.; Horng, M.-M.; Chong, K.-T.; Hinshaw, R. R.; Dolak, L. A.; Schwende, F. J.; Rush, B. D.; Howard, G. M.; Toth, L. N.; Wilkinson, K. F.; Kakuk, T. J.; Johnson, C. W.; Cole, S. L.; Zaya, R. M.; Zipp, G. L.; Possert, P. L.; Dalga, R. J.; Romines, K. R. J. Med Chem., in press.
6. 6. Romines, K. R.; Watenpaugh, K. D.; Howe, W. J.; Tomich, P. K.; Lovasz, K. D.; Morris, J. K.; Janakiraman, M. N.; Lynn, J. C.; Horng, M.-M.; Chong, K.-T.; Hinshaw, R. R.; Dolak, L. A. J. Med. Chem. 1995, 38, 4463.
7. 7. The alcohol (5) was prepared by treatment of 3-bromobenzyl alcohol with methyllithium, n-butyllithium and cyclopropanecarboxaldehyde in sequence at -78 oC.
8. 8. In vitro inhibition of HIV-1 protease was measured as described in the following: Thaisrivongs, S.; Tomich, P. K.; Watenpaugh, K. D.; Chong, K.-T.; Howe, W. J.; Yang, C.-P.; Strohbach, J. W.; Turner, S. R.; Spinelli, P. A.; Hinshaw, R. R.; Pagano, P. J.; Moon, J. B.; Ruwart, M. J.; Wilkinson, K. F.; Rush, B. D.; Zipp, G. L.; Dalga, R. J.; Schwende, F. J.; Howard, G. M.; Padbury, G. E.; Toth, L. N.; Zhao, Z.; Koeplinger, K. A.; Kakuk, T. J.; Cole, S. L.; Zaya, R. M.; Piper, R. C.; Jeffrey, P. J. Med. Chem. 1994, 37, 3200.
9. 9. Antiviral activity was measured as described in the following: Chong, K.-T.; Pagano, P. J.; Hinshaw, R. R. Antimicrob. Agents Chemother. 1994, 38, 288.
10. 10. Transcellular flux was measured as described in the following: Sawada, G. A.; Ho, N. F. H.; Williams, L. R.; Barsuhn, C. L.; Raub, T. J. Pharm. Res. 1994, 11, 665.
11. 11. Conradi, R. A., Hilgers, A. R.; Ho, N. F. H., Burton, P. S. Pharm. Res. 1991, 8, 1453.
12. 12. Raub, T. J., Skulnick, H. I., Toth, L. N., Padbury, G. E., unpublished result.
13. 13. The preparation of compounds of the general type 14 may be found in ref. 5.