Table 3.
Analogs of 3 containing different linker moieties.
| Cmpd | L | R1, R2, R3 | EC50 (μM)b | S9 stability T1/2 (min) |
||
|---|---|---|---|---|---|---|
| Influenza | MeV | human | hamster | |||
| 3 | - | - | 0.5 | 0.74 | 19 | <2.5 |
| 12 |
|
R1=R2=R3=4-H | 0.4 | 6.0 | 15 | 3 |
| 14a |
|
R1=R2=R3=4-F | 8.0 | 5.0 | <2.5 | <2.5 |
| 14b |
|
R1=R2=R3=H | >10 | >10 | NDc | ND |
| 15 |
|
R1=R2=R3=4-F | >10 | >10 | >90 | 54 |
| 23a |
|
R1=R2=R3=H | >10 | >10 | 27 | <2.5 |
| 24a |
|
R1=R2=H, R3=2-F | 10.0 | 9.0 | ND | ND |
| 24b |
|
R1=R2=H, R3=2-NO2 | 6.0 | 9.0 | ND | ND |
| 25 |
|
Rl=R2=R3=H | 10 | >10 | >90 | 5 |
| 26 |
|
Rl=R2=R3=H | >10 | >10 | ND | ND |
| 27 |
|
Rl=R2=R3=H | 10.0 | 6.0 | ND | ND |
| 28a |
|
Rl=R2=R3=H | 0.88 | 0.91 | 165 | <5.0 |
| 28b |
|
R1=R2=H, R3=4-OH | 10 | 10 | ND | ND |
| 28c |
|
R1=R2=H, R3=2-COOH | 3 | 3 | ND | ND |
| 28d |
|
R1=R2=H, R3=2-Py | 10 | 10 | ND | ND |
| 32a |
|
R1=R2=R3=H | >10 | >10 | ND | ND |
| 32b |
|
R1=R2=R3=H | 10 | 10 | ND | ND |
a
Lacks 1-methyl group on imidazole ring.
b
50% inhibitory concentration were calculated using the variable slope (four parameters) non-linear regression-fitting algorithm embedded in the Prism 5 software package (GraphPad Software). Values represent averages of four assessments; highest concentration assessed,10 μM.
c
Not determined when EC50 >10 μM.