Table 1.
Schematic summary of contribution of each atom and moiety discussed in the present work.
| DRV, GRL-142, and their analogs | Mean IC50 ± SD (nM) | |||||
|---|---|---|---|---|---|---|
| Inhibitors | P1 | P2′ | HIVWT | HIVDRVRP20 | HIVDRVRP30 | HIVDRVRP51 |
| DRV (MW: 547.66) |  |
 |
5.1 (± 1.6) | 42.0 (± 2.7) | 342.0 (± 38) | >1000 |
| GRL-142 (MW: 706.82) |  |
 |
0.0094 (± 0.018) | 0.00038 (± 0.00031) | 0.0027 (± 0.0018) | 4.1 (± 0.2) |
| GRL-121 (MW: 670.84) |  |
 |
0.44 (± 0.069) | 1.7 (± 0.53) | 2.9 (± 0.80) | 74.0 (± 10) |
| GRL-001 (MW: 688.83) |  |
 |
0.059 (± 0.0093) | 0.92 (± 0.14) | 7.4 (± 1.2) | 31.0 (± 4.2) |
| GRL-002 (MW: 674.79) |  |
 |
0.29 (± 0.055) | 54.0 (± 3.0) | 394.0 (± 35) | 625.0 (± 75) |
| GRL-003 (MW: 688.83) |  |
 |
0.048 (± 0.012) | 5.3 (± 0.86) | 26.0 (± 6.9) | 73.0 (± 9.6) |
| GRL-004 (MW: 674.79) |  |
 |
0.12 (± 0.03) | 61.0 (± 10) | 319.0 (± 55) | 763.0 (± 167) |
| GRL-063 (MW: 692.78) |  |
 |
0.055 (± 0.0019) | 0.57 (± 0.056) | 4.0 (± 0.42) | 40.0 (± 0.3) |
| GRL-011 (MW: 690.84) |  |
 |
1.2 (± 0.39) | 7.3 (± 0.23) | 44.0 (± 4.0) | 381.0 (± 111) |
| GRL-014 (MW: 690.84) |  |
 |
0.61 (± 0.043) | 8.5 (± 0.51) | 52.0 (± 16) | 256.0 (± 96) |
| GRL-015 (MW: 672.76) |  |
 |
1.3 (± 0.40) | 61.0 (± 3.8) | 345.0 (± 28) | 622.0 (± 31) |
| GRL-016 (MW: 708.83) |  |
 |
0.046 (± 0.0086) | 2.9 (± 0.81) | 30.0 (± 0.69) | 30.0 (± 8.1) |
Meta- or para-fluoro-substitution of fluorine almost equally contributed the cell permeability and antiviral activity, whereas the cell permeability and antiviral activity gained boost with dual fluorine at meta position. Benzothiazole-containing inhibitors performed overall better in their antiviral activity compared to benzoxazole-containing inhibitors. Cyclopropyl-containing inhibitors exerted greater antiviral activity than isopropyl-containing inhibitors.