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4. Zhuang, L.; Wai, J. S.; Embrey, M. W.; Fisher, T. S.;
Egbertson, M. S.; Payne, L. P.; Guare, J. P., Jr.; Vacca, J. P.;
Hazuda, D. J.; Felock, P. J.; Wolfe, A. L.; Stillmock, K. A.;
Witmer, M. V.; Moyer, G.; Schleif, W. A.; Gabryelski, L. J.;
Leonard, Y. M.; Lynch, J. J., Jr.; Michelson, S. R.; Young,
S. D. J. Med. Chem. 2003, 46, 453.
5. Hazuda, D. J.; Anthony, N. J.; Gomez, R. P.; Jolly, S. M.;
Wai, J. S.; Zhuang, L.; Fisher, T. E.; Embrey, M.; Guare,
J. P., Jr.; Egbertson, M. S.; Vacca, J. P.; Huff, J. R.;
Felock, P. J.; Witmer, M. V.; Stillmock, K. A.; Danovich,
R.; Grobler, J.; Miller, M. D.; Espeseth, A. S.; Jin, L.;
Chen, I-W.; Lin, J. H.; Kassahun, K.; Ellis, J. D.; Wong,
B. K.; Xu, W.; Pearson, P. G.; Schleif, W. A.; Cortese, R.;
Emini, E.; Summa, V.; Holloway, M. K.; Young, S. D.
Proc. Natl. Acad. Sci. 2004, 101, 11233.
proved that 38 did not inhibit human DNA polymerase
a, b, and c or HIV-RT. The efforts made to improve the
potency of this novel class of HIV integrase inhibitors in
cell-based assay will be reported elsewhere.12
In conclusion, dihydroxypyrimidine carboxamides were
identified as a novel and selective class of HIV-1 inte-
grase inhibitors. SAR around the carboxamide moiety
generated low nanomolar inhibitors which have poten-
tial for future development as anti-HIV agents.
Acknowledgments
6. Summa, V.; Petrocchi, A.; Pace, P.; Matassa, V.; De
Francesco, R.; Altamura, S.; Tomei, L.; Koch, U.;
Neuner, P. J. Med. Chem. 2004, 47, 14.
7. Pace, P.; Nizi, E.; Pacini, B.; Pesci, S.; Matassa, V.; De
Francesco, R.; Altamura, S.; Summa, V. Bioorg. Med.
Chem. Lett. 2004, 14, 3257.
We thank Odalys Paz Gonzalez and Ralph Laufer for
PK studies; William B. Schleif and Peter J. Felock for
biological testing; Steven Harper and Michael Rowley
for their helpful support and suggestions. This work
was supported in part by a grant from the MIUR.
8. Summa, V.; Petrocchi, A.; Matassa, V.; Taliani, M.;
Laufer, R.; De Francesco, R.; Altamura, S.; Pace, P. J.
Med. Chem. 2004, 47, 5336.
References and notes
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12. Summa, V., et al. J. Med. Chem., in press.