Table 1.
Inhibitory potency against SARS-CoV-2 3CLpro. Evaluation of warheads (R1)[].
| Entry | Scaffold | Cmpd | R1 | Inhibition (%)a | IC50 (μM) |
|---|---|---|---|---|---|
| 1 | – | GC376 | – | >95 | 0.11 ± 0.06 |
| 2 | I | X77 |  |
>95 | 4.1 ± 1.2 |
| 3 | Ic | ML188 |  |
>95 | 1.4 ± 0.4 |
| 4 | I | 4a |  |
25 ± 8 | ndb |
| 5 | I | 5a |  |
28 ± 3 | ndb |
| 6 | I | 6a |  |
84 ± 1 | 11.1 ± 1.5 |
| 7 | I | 7a |  |
44 ± 6 | ndb |
| 8 | I | 8a |  |
63 ± 5 | ndb |
| 9 | I | 9a |  |
47 ± 2 | ndb |
| 10 | I | 10a |  |
30 ± 1 | ndb |
| 11 | I | 11a |  |
55 ± 10 | ndb |
| 12 | I | 12a |  |
52 ± 1 | ndb |
| 13 | I | 13a |  |
>95 | 5.3 ± 0.8 |
| 14 | I | 14a |  |
>95 | 0.42 ± 0.11 |
| 15 | I | 15a |  |
30 ± 7 | ndb |
| 16 | I | 16a |  |
>95 | 0.41 ± 0.13 |
| 17 | I | 17a |  |
59 ± 6 | ndb |
| 18 | I | 18a |  |
92 ± 1 | 5.2 ± 1.2 |
| 19 | I | 19a |  |
35 ± 3 | ndb |
| 20 | I | 20a |  |
74 ± 1 | 7.0 ± 0.2 |
| 21 | I | 21a |  |
<5 | ndb |
| 22 | I | 22a |  |
77 ± 4 | 12.4 ± 5.2 |
| 23 | I | 23a |  |
>95 | 0.85 ± 0.42 |
| 24 | II | 24a |  |
25 ± 1 | ndb |
| 25 | II | 25a |  |
<5 | ndb |
a The enzyme activity was measured with 150 nM 3CLpro (114 nM after inhibitor addition) and 50 μM of each potential inhibitor with incubation time of 30 min b not determined. c cyclohexyl replaced by tert-butyl in scaffold I.