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R. N. Brown et al. / Bioorg. Med. Chem. Lett. 15 (2005) 2051–2055
Table 3. Activity of compound 13 against a representative panel of HRV serotypes
HRV
serotype
EC50 SDa (ng/mL)
for Pleconaril 1
EC50 SDa (ng/mL)
for Pirodavir 2
EC50 SDa (ng/mL)
for oxime ether 3
EC50 SDa (ng/mL)
for benzoxazole 13
2
26.47 13.84
37.16 15.44
34.31 15.57
69.80 10.19
108.03 44.55
45.40 29.27
44.88 7.78
1908 910
2.77 2.23
2.05 1.05
3.65 1.95
7.92 2.92
15.24 6.25
3.74 2.59
1.80 1.92
>5000
9.23 8.72
1.09 0.74
1.78 3.05
7.77 2.84
11.12 5.86
5.99 4.13
2.89 2.86
>5000
1.16 0.81
1.20 1.01
4.32 1.27
4.33 1.70
7.72 3.53
7.28 7.10
0.53 0.023
>250 (n = 3)
3.45 1.13
2.26 1.90
0.30 0.11
15.23 9.00
142.27 46.62
0.78 0.30
8.74 2.71
1.51 0.71
3.88
9
14
15
16
29
39
45
51
59
63
70
72
85
86
89
Median
30.40 16.95
387.33 314.13
62.30 13.98
53.87 14.16
468.70 299.52
34.00 30.56
70.04 17.23
29.33 45.99
49.63
5.21 4.50
4.37 3.17
0.83 0.57
2.14 0.71
34.77 6.07
4.72 5.59
9.56 6.72
5.70 1.90
4.54
2.90 2.15
5.08 2.93
2.06 2.18
3.13 1.61
21.01 8.93
7.90 6.94
4.42 2.25
0.83 0.71
4.75
None of the compounds showed significant cytotoxicity at the highest concentration (1–5 lg/mL).
a For calculation of the EC50 and standard deviation (SD) all assays were run at least six times.
Rosenwirth, B. J. Mol. Biol. 1996, 259, 120; (c) Giranda,
V. L.; Russo, G. R.; Felock, P. J.; Bailey, T. R.; Draper,
T.; Aldous, D. J.; Guiles, J.; Dutko, F. J.; Diana, G. D.;
Pevear, D. C. Acta Crystallogr. 1995, D51, 496.
9. Diana, G.; Jaeger, E. P.; Peterson, M. L.; Treasurywala,
A. M. J. Comput. Aided Mol. Des. 1993, 7, 325.
10. Andries, K.; Dewindt, B.; Snoeks, J.; Willebrords, R.;
VanEemeren, K.; Stokbroekx, R.; Janssen, P. A. J.
Antimicrob. Agents Chemother. 1992, 36, 100.
herein are an interesting example of the 2-alkoxy benzo-
azole ring system acting as a bioisosteric replacement of
an aryl ester or an aryl oxime ether group.24
Acknowledgements
We gratefully acknowledge Dr. Wen-Yang Wu and Dr.
Jane Ryan for helpful and encouraging discussions. We
also acknowledge the financial assistance of a START
grant from the Australian Government.
11. Andries, K. In The Search for Antiviral Drugs; Adams, J.,
Merluzzi, V. J., Eds.; Birkhauser: Boston, 1993; pp 179–
209.
12. Hayden, F. G.; Andries, K.; Janssen, P. A. J. Antimicrob.
Agents Chemother. 1992, 36, 727.
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strains, generally HRV2 and HRV14, using standard cell
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