Table 1.
Inhibitory properties for yellow fever virus and dengue virus of the imidazole analogs 15a–15o.
| Sr. No. | n1 | n2 | R1 | R2 | Heterocycle (positiona) | Dengue |
Yellow fever |
||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| EC50 (μM) | CC50 (μM) | SI | EC50 (μM) | CC50 (μM) | SI | ||||||
| 15a | 0 | 0 | F | p-Methyl | 3-Methyl-1H-pyrazol-5-yl (ortho) Initial Lead | 2.50 | >120 | 48 | 3.47 | >120 | 34.5 |
| 15b | 0 | 0 | F | H | 3-Methyl-1H-pyrazol-5-yl (ortho) | 6.03 | 21.7 | 3.6 | 1.85 | >121 | 67 |
| 15c | 0 | 1 | F | H | Pyridin-4-yl (ortho) | 1.93 | 50.1 | 26 | 3.90 | >120 | 31 |
| 15d | 0 | 1 | F | H | Thien-3-yl (ortho) | 8.88 | 17.32 | 1.95 | 2.61 | 34.5 | 13.2 |
| 15e | 0 | 1 | F | H | Pyridin-3-yl (para) | 42.10 | >120 | 2.85 | 11.81 | >118 | 10 |
| 15f | 0 | 1 | F | H | Thien-3-yl (para) | 33.69 | 20.21 | 0.60 | 28.77 | >119 | 4.13 |
| 15g | 0 | 1 | F | H | Pyridin-4-yl (para) | >120 | >120 | 1 | >120 | >120 | 1 |
| 15h | 0 | 0 | F | p-Methyl | Thien-3-yl (ortho) | 48.75 | >117 | 2.4 | >119 | >119 | 1 |
| 15i | 0 | 0 | F | p-Methyl | Furan-2-yl (ortho) | >123.6 | >124 | 1 | ND | – | – |
| 15j | 0 | 0 | H | p-Methyl | Thien-3-yl (ortho) | >124 | >124 | 1 | 9.20 | >120 | 13 |
| 15k | 0 | 0 | CH3 | p-Methyl | Thien-3-yl (ortho) | 2.02 | >50 | 24.5 | >120 | >120 | 1 |
| 15l | 0 | 0 | CH3 | p-Methyl | Furan-2-yl (ortho) | 3.47 | >125 | 36.2 | ND | – | – |
| 15m | 1 | 0 | H | p-Methyl | Furan-2-yl (ortho) | >125 | >125 | 1 | ND | – | – |
| 15n | 2 | 0 | F | p-Methyl | Furan-2-yl (ortho) | 3.77 | >116.5 | 30.9 | ND | – | – |
| 15o | 0 | 0 | H | p-Methyl | See structure above | >120 | 26.40 | 0.22 | >120 | >119 | 0.97 |
a
Indicates the attachment point of the heterocycle on the phenyl ring.