Skip to main content
. Author manuscript; available in PMC: 2012 May 1.
Published in final edited form as: Bioorg Med Chem. 2011 Mar 23;19(9):2950–2958. doi: 10.1016/j.bmc.2011.03.034

Table 1.

Antiviral Activity of Metabolically Stable Alkoxyalkyl Prodrugs of CDV and (S)-HPMPA against Orthopoxviruses

Ectromelia Cowpox Vaccinia
Compound EC50 CC50 S.I. EC50 CC50 S.l. EC50 CC50 S.I.
Cidofovir compounds
HDP-CDV 0.125 ± 0.06 25.3 ± 7.5 202 0.2 ± 0.1 25 ± 9.5 125 0.08 ± 0.03 25 ± 9.5 313
15M-HDP-CDV 0.043 ±0.007 78.0 ± 9.9 1810 0.1 ± 0.04 15 ± 4.0 150 0.2 ± 0.06 15 ± 4.0 75
14-cp-TDP-CDV 0.74 ± 0.22 74.0 ± 4.5 100 0.5 ± 0.05 56 ± 13 112 0.3 ± 0.2 56 ± 13 187
ODBG-CDV 0.03 ± 0.007 351 1100 0.3 ± 0.12 47 ± 24 157 0.4 ± 0.12 47 ± 24 118
13M-TDP-CDV 0.39 ± 0.12 82 210 0.3 ± 0.1 37 ± 5.6 123 0.3 ± 0.2 37 ± 5.6 123
12M-TRDP-CDV 0.35 ± 0.07 82 234 0.8 ± 0.2 44 ± 4.0 55 1.0 ± 0.4 44 ± 4.0 44
(S)-HPMPA compounds
HDP-(S)-HPMPA 0.066 ± .014 84.7 ± 26.4 1280 0.02 ± .006 2.8 ± 1.3 140 0.01 ± 0.006 2.8 ± 1.3 280
15M-HDP-(S)-HPMPA 0.044 ± 0.016 11.7 ± 5 266 0.04 ± 0.02 11.4 ± 14 285 0.04 ± 0.03 11.4 ± 14 285
HDNE-(S)-HPMPA 0.32 ± 0.12 2.32 ± 0.94 7.2 0.02 ±0.002 1.7 ± 0.9 85 0.02 ± 0.004 1.7 ± 0.9 85
HDE-(S)-HPMPA 0.14 ± 0.06 40.5 ± 17.5 289 0.09 ± 0.03 14 ± 1.9 156 0.09 ± 0.05 14 ± 1.9 156
15M-HDE-(S)-HPMPA 0.01 ±0.006 59.6 ± 16.7 5960 0.01 ±0.005 2.5 ± 0.1 250 0.01 ± 0.002 2.5 ± 0.1 250

Data are μM, mean ± SD (n=3). When no SD is given the result is the average of two determinations. Abbreviations: HDP-CDV, hexadecyloxypropyl-cidofovir; 15M-HDP-CDV, 15-methyl-hexadecyloxypropyl-cidofovir; 14-cp-TDP-CDV, 14-cyclopropyl-tetradecyloxypropyl-cidofovir; ODBG-CDV, 1-O-octadecyl-2-O-benzyl-sn-glyceryl-3-cidofovir ; 13M-TDP-CDV, 13-methyl-tetradecyloxypropyl-cidofovir; 12M-TRDP-CDV, 12-methyl-tridecyloxypropyl-cidofovir; HDP-(S)-HPMPA; hexadecyloxypropyl-(S)-HPMPA, 15M-HDP-(S)-HPMPA, 15-methyl-hexadecyloxypropyl-(S)-HPMPA; HDNE-(S)-HPMPA, ω-hexadecenyloxyethyl-(S)-HPMPA, HDE-(S)-HPMPA, hexadecyloxyethyl-(S)-HPMPA; 15M-HDE-(S)-HPMPA, 15-methyl-hexadecyloxyethyl-(S)-HPMPA. SI, selective index; EC50, 50% effective concentration; CC50, 50% cytotoxic concentration as μM. Antiviral assays are plaque reduction assays as noted in Methods.

1

Hostetler, K. Y. et al. Antiviral Res. 2007, 73, 212.;

2

Keith, K. A. et al. Antimicrob. Agents Chemother., 2004, 48, 1869.