Table 4.
In vitro metabolic stability of 2,6-diarylpyrazine diamidine prodrugs
| Code | Mouse t1/2 (min)a | Human t1/2 (min)a |
|---|---|---|
| 2b | 29 ± 10# | NDb |
| 2c | 150 ± 10c | 6.8 ± 2c |
| 11 | 1.9 ± 0.1# | ND |
| 12 | 26 ± 6 | 8.6 ± 0.9 |
| 20a | 30 ± 4# | ND |
| 21a | 210 ± 100 | 7.6 ± 0.3 |
| 20b | 36 ± 5# | ND |
| 21b | 35 ± 6 | 6.5 ±1.2 |
| 24a | 20 ± 0.4# | ND |
| 25a | 200 ± 70 | 70 ± 23 |
| 24b | 51 ± 1.4# | ND |
| 25b | 59 ± 10 | 14 ± 6 |
#
Bis-amidoxime prodrugs were incubated with mouse liver S9 fraction, instead of liver microsomes.
a
Mean ± standard deviations of triplicate determinations.
b
ND, not determined.
c
Substrate concentration for 2c was 3 μM and its t1/2 was shown as mean and range of duplicate determinations.