1358
A. Thorarensen et al. / Bioorg. Med. Chem. Lett. 11 (2001) 1355–1358
Table 3. Antibacterial andPDF activity of a-hetero substituted
acetoamides
4. (a) Setti, E. L.; Micetich, R. G. Curr. Med. Chem. 1998, 5,
101. (b) Katz, L.; Chu, D. T.; Reich, K. Annu. Rep. Med.
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SAUR
9218 MIC 12084 MIC 9912 MIC 6674 MIC IC50
SEPI
SPNE
ECOL
PDF
(mM)
6. Trias, J.; Gordon, E. M. Curr. Opin. Biotechnol. 1997, 8,
757.
15 CH2SH
16 CH2OH
17 NHNH2
18 NHOH
>128
32
>128
32
>128
>128
>128
32
>128
32
>128
32
>128
>128
>128
>128
>100
>100
>100
7. Ragusa, S.; Blanquet, S.; Meinnel, T. J. Mol. Biol. 1998,
280, 515.
8. (a) Dardel, F.; Ragusa, S.; Lazennec, C.; Blanquet, S.;
Meinnel, T. J. Mol. Biol. 1998, 280, 501. (b) O’Connell, J. F.;
Pryor, K. A. D.; Grant, S. K.; Leiting, B. J. Biomolecular
NMR 1999, 13, 311.
2.2
9. (a) Becker, A.; Schlichting, I.; Kabsch, W.; Groche,
D.; Schultz, S.; Wagner, A. F. V. Nat. Struct. Biol. 1998,
5, 1053.
10. Hao, B.; Gong, W.; Rajagopalan, P. T. R.; Zhou, I.; Pei,
D.; Chan, M. K. Biochemistry 1999, 38, 4712.
11. Chen, D. Z.; Patel, D. V.; Hackbarth, C. J.; Wang, W.;
Dreyer, G.; Young, D. C.; Margolis, P. S.; Wu, C.; Ni, Z-
J.; Trias, J.; White, R. J.; Yuan, Z. Biochemistry 2000, 39,
1256.
problem andfulfills our initial goal of a PDF inhibitor
with antibacterial activity. The SAR of this general
template andthe optimization of its antibacterial activ-
ity along with the search of additional polar functional
groups will be the topic of future reports.
Acknowledgements
12. Apfel, C.; Banner, D. W.; Bur, D.; Dietz, M.; Hirata, T.;
Hubschwerlen, C.; Locher, H.; Page, M. G. P.; Pirson, W.;
Rosse, G.; Specklin, J.-L. J. Med. Chem. 2000, 43, 2324.
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taker, M.; Davies, S. J.; Pratt, L. M.; Spavold, Z. M.;
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59097.
We acknowledge the Structural, Analytical and Medic-
inal Chemistry Unit at Pharmacia for analytical ser-
vices. Thanks to DavidR. Graber andSteven P. Tanis
for information andhelp regarding the preparation of
compounds 8–11, andto Bruce N. Rogers for critical
reading of this manuscript.
14. Huntington, K. M.; Yi, T.; Wei, Y.; Pei, D. Biochemistry
2000, 39, 4543.
References and Notes
15. Green, B. G.; Toney, J. H.; Kozarich, J. W.; Grant, S. K.
Arch. Biochem. Biophys. 2000, 375, 355.
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G. P., Luscombe, D. K., Eds.; Elsevier Science: New York,
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16. Preliminary disclosure: Identification of Novel Potent
Hydroxamic Acid Inhibitors of Peptidyl Deformylase; Poster,
French–American Chemical Society FACS VIII, Sonoma
County, CA, June 2000.
17. (a) Wei, Y.; Pei, D. Anal. Biochem. 1997, 250, 29. (b)
Lazennec, C.; Meinnel, T. Anal. Biochem. 1997, 244, 180.
18. Compounds not shown but are related to 16.
19. The antibacterial activity of 16 is due to an unknown
mechanism andappears to be unrelatedto PDF.