Nonpeptidic HIV protease inhibitors: 4-hydroxy-pyran-2-one inhibitors with functional tethers to P1 phenyl ring to reach S3 pocket of the enzyme

Biochemical and Biophysical Research Communications

Volumn 221, Issue 3, 1996, Pages 815-820

  Vara Prasad, J V N ^a   Tummino, Peter J ^a   Ferguson, Donna ^a   Saunders, James ^a   Vander Roest, Steve ^a   McQuade, Thomas J ^a   Heldsinger, Andrea ^a   Reyner, Eric L ^a   Stewart, Barbra H ^a   Guttendorf, Robert J ^a   Para, Kimberly S ^a   Lunney, Elizabeth A ^a   Gracheck, Stephen J ^a   Domagala, John M ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 HYDROXY PYRAN 2 ONE; PROTEINASE; PROTEINASE INHIBITOR; UNCLASSIFIED DRUG; VIRUS ENZYME;

ARTICLE; BINDING AFFINITY; DRUG STRUCTURE; ENZYME INHIBITION; ENZYME INHIBITOR INTERACTION; HUMAN IMMUNODEFICIENCY VIRUS; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION;

CELL LINE; HIV PROTEASE INHIBITORS; HIV-1; HUMANS; MOLECULAR STRUCTURE; PYRONES;

HUMAN IMMUNODEFICIENCY VIRUS;

EID: 0030006980     PISSN: 0006291X     EISSN: None     Source Type: Journal    
DOI: 10.1006/bbrc.1996.0679     Document Type: Article

References (18)

1. Darke, P. L., Huff, J. R. (1994) in Advances in Pharmacology (August, J. T., Ander, M. W., and Murad, F. Eds.), Vol. 265, pp. 399-454, Academic Press, San Diego.
2. Thaisrivongs, S. (1994) in Annual Reports in Medicinal Chemistry (Bristol, J., Ed.), Vol. 17, pp. 133-144 and references therein.
3. Condra, J. H., Schleif, W. A., Blahy, O. M., Gabryelski, L. J., Graham, D. J., Quintero, J. C., Rhodes, A., Robbins, H. L., Ropth, E., Shivaprakash, M., Titus, D., Yang, T., Teppler, H., Squires, K. E., Deutsch, P. J., and Emihi, E. A. (1995) Nature 374, 569-571.
4. Tummino, P. J., Ferguson, D., Hupe, L., and Hupe, D. (1990) Biochem. Biophys. Res. Commun. 200, 1658-1664.
5. Vara Prasad, J. V. N., Para, K. S., Lunney, E. A., Ortwine, D. F., Dunbar, Jr., 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., and Sawyer, T. K. (1994) J. Am. Chem. Soc. 116, 6989-6990.
6. Vara Prasad, J. V. N., Para, K. S., Tummino, P. J., Ferguson, D., McQuade, T. J., Lunney, E. A., Rapundalo, S. T., Bately, B. L., Hingorani, G., Domagala, J. M., Gracheck, S. J., Bhat, T. N., Liu, B., Baldwin, E. T., Erickson, J. W., and Sawyer, T. K. (1995) J. Med. Chem. 38, 898-905.
7. Thaisrivongs, S., Tomich, P. K., Watenpaugh, K. D., Chong, K-T., Howe, W. J., Yang, C-P., Strohbach, J. W., Turner, S. R., McGrath, J. P., Bohanon, M. J., Lynn, J. C., Mulichak, A. M., 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., and Jeffrey, P. (1994) J. Med. Chem. 37, 3200-3204.
8. 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., and Erickson, J. W. (1995) J. Am. Chem. Soc. 117, 11070-11074.
9. Romines, K. R., and Thaisrivongs, S. (1995) Drugs of the Future 20, 377-382.
10. Thomson, W. J., Fitzgerald, P. M. D., Holloway, K., Emini, E. A., Darke, P. L., McKeever, B. M., Schleif, W. A., Quintero, J. C., Zugay, J. A., Tucker, T. J., Schwering, J. E., Hommick, C. F., Nunberg, J., Springer, J. P., and Huff, J. R. (1992) J. Med. Chem. 35, 1685-1701.
11. Kim, B. M., Guare, J. P., Vacca, J. P., Michelson, S. R., Darke, P. L., Zugay, J. A., Emini, E. A., Schleif, W., Lin, J. H., Chen, I. W., Vastag, K., Andersen, P. S., and Huff, J. R. (1995) Biorog. Med. Chem. Lett. 5, 185-190.
12. 3 pocket of the enzyme: Thaisrivongs, S., Watempaugh, K. D., Howe, W. J., Tomich, P. K., Dolak, L. A., Chong, K-T., Shen, C-S., Tomasselli, A. G., Turner, S. R., Strobach, J. W., Mulichak, A. M., Janakiraman, M. N., Moon, J. B., Lynn, J. C., Horng, M-M., Hinshaw, R. R., Curry, K. A., and Rothrock, D. J. (1995) J. Med. Chem. 38, 3624-3637.
13. Kempf, D. J., Codacovi, L., Wang, X. C., Kohlbrenner, W. E., Wideburg, N. E., Saldivar, A., Vasavanonda, S., Marsh, K. C., Bryant, P., Sham, H. L., Green, B. E., Betebenner, D. A., Erickson, J., and Norbeck, D. W. (1993) J. Med. Chem. 36, 320-330.
14. Para, K. S., Ellsworth, E. L., and Vara Prasad, J. V. N. (1994) J. Het. Chem. 31, 1619-1624.
15. Vara Prasad, J. V. N., Lunney, E. A., Para, K. S., Tummino, P. J., Ferguson, D., Hupe, D., Domagala, J. M., and Erickson, J. W. (1995) Drug Design and Discovery, (Press).
16. Buckheit, Jr., R., Hollingshead, M. G., Germany-Decker, J., White, E. L., McMohan, J. B., Allen, L. B., Ross, L. J., Decker, W. D., Westbrook, L., Shannon, W. M., Weislow, O., Bader, J. P., and Boyd, M. R. (1993) Antiviral Research 21, 247-265.
17. Bos, O. J. M., Fische, M. J. E., Wilting, J., and Janssen, L. H. M. (1989) Biochem. Pharm. 38, 1979 and references therein.
18. Stewart, B. H., Chan, O. H., Lu, R. H., Reyner, E. L., Schmid, H. L., Hamilton, H. W., Steinbaugh, B. A., and Taylor, M. D. (1995) Pharm. Res. 12, 693-699.