COVID Moonshot Sprint 11A for optimizing 5-spiro compounds based on P1800_0A using reference compound VLA-UCB-50c39ae8-2 with Mpro dimer and charged Cys145:His41 catalytic dyad
| Rank | Compound | SMILES | ΔG / kcal mol-1 | pIC50 | |
|---|---|---|---|---|---|
| 1 | DAR-DIA-0f7b7cd9-9 |
|
c1ccc2c(c1)cncc2N3CC(=O)C4(C3=O)CCOc5c4cc(cc5)Cl | −11.4 ± 0.1 | 8.28 ± 0.09 |
| 2 | ALP-POS-477dc5b7-4 |
|
c1ccc2c(c1)cncc2N3CCC4(C3=O)CCOc5c4cc(cc5)Cl | −10.95 ± 0.10 | 7.97 ± 0.07 |
| 3 | EDJ-MED-159244ea-1 |
|
c1ccc2c(c1)cncc2N3CC[C@]4(C3=O)CCOc5c4cc(cc5)Cl | −10.82 ± 0.09 | 7.88 ± 0.06 |
| 4 | VLA-UNK-cf7facf1-1 |
|
c1ccc2c(c1)cncc2N3C(=O)[C@]4(CCOc5c4cc(cc5)Cl)NC3=O | −10.66 ± 0.09 | 7.77 ± 0.06 |
| 5 | VLA-UCB-34f3ed0c-11 |
|
c1ccc2c(c1)cncc2N3C(=O)[C@@]4(CCOc5c4cc(cc5)Cl)NC3=O | −10.54 ± 0.09 | 7.68 ± 0.06 |
| 6 | DAR-DIA-6be260fc-5 |
|
c1ccc2c(c1)cncc2N3CCC4(C3=O)CCNc5c4cc(cc5)Cl | −10.5 ± 0.2 | 7.7 ± 0.1 |
| 7 | MAT-POS-983b399a-1 |
|
c1ccc2c(c1)cncc2N3CCC4(C3=O)CCOc5c4cc(cc5)Cl | −10.4 ± 0.1 | 7.60 ± 0.08 |
| 8 | VLA-UCB-29506327-1 |
|
c1ccc2c(c1)cncc2N3C(=O)C4(CCOc5c4cc(cc5)Cl)NC3=O | −10.43 ± 0.10 | 7.60 ± 0.07 |
| 9 | PET-UNK-aa57768f-9 |
|
C#CCN1CC2(CCN(C2=O)c3cncc4c3cccc4)c5cc(ccc5C1=O)Cl | −10.3 ± 0.2 | 7.5 ± 0.1 |
| 10 | BEN-BAS-c2bc0d80-3 |
|
c1ccc2c(c1)cncc2N3C(=O)C4(CCOc5c4cc(cc5)Cl)CN3 | −10.09 ± 0.10 | 7.35 ± 0.07 |
| 11 | MAT-POS-90505e2b-1 |
|
c1ccc2c(c1)cncc2N3C(=O)C4(CCOc5c4cc(cc5)Cl)OC3=O | −9.62 ± 0.07 | 7.01 ± 0.05 |
| 12 | BEN-BAS-c2bc0d80-7 |
|
CN1C(=O)N(C(=O)C12CCOc3c2cc(cc3)Cl)c4cncc5c4cccc5 | −9.6 ± 0.1 | 6.99 ± 0.08 |
| 13 | MAT-POS-ec6d90b7-2 |
|
c1ccc2c(c1)cncc2N3C(=O)[C@]4(CCOc5c4cc(cc5)Cl)OC3=O | −9.54 ± 0.09 | 6.95 ± 0.06 |
| 14 | VLA-UNK-3a43cd95-1 |
|
c1ccc2c(c1)cncc2N3C(=O)[C@@]4(CCOc5c4cc(c(c5)F)Cl)NC3=O | −9.39 ± 0.09 | 6.84 ± 0.07 |
| 15 | MAT-POS-ec6d90b7-1 |
|
c1ccc2c(c1)cncc2N3C(=O)[C@@]4(CCOc5c4cc(cc5)Cl)OC3=O | −9.09 ± 0.07 | 6.62 ± 0.05 |
| 16 | VLA-UCB-05e51b3f-5 |
|
c1ccc2c(c1)cncc2N3C(=O)C[C@]4(C3=O)CCOc5c4cc(cc5)Cl | −9.07 ± 0.04 | 6.61 ± 0.03 |
| 17 | VLA-UCB-50c39ae8-2 |
|
c1ccc2c(c1)cncc2N3C(=O)C[C@@]4(C3=O)CCOc5c4cc(cc5)Cl | −9.07 ± 0.04 | 6.61 ± 0.03 |
| 18 | BEN-BAS-c2bc0d80-6 |
|
c1ccc2c(c1)cncc2N3C(=O)CC4(C3=O)CCOc5c4cc(cc5)Cl | −9.07 ± 0.04 | 6.61 ± 0.03 |
| 19 | MAT-POS-94643566-1 |
|
c1ccc2c(c1)cncc2N3C(=O)CC4(C3=O)CCOc5c4cc(cc5)Cl | −9.05 ± 0.05 | 6.59 ± 0.04 |
| 20 | BRU-THA-73c97d88-1 |
|
c1ccc2c(c1)cncc2N3C(=O)C4(CCOc5c4cc(cc5)Cl)C=N3 | −8.65 ± 0.08 | 6.30 ± 0.06 |
| 21 | VLA-UNK-56836b69-2 |
|
c1ccc2c(c1)cncc2N3C(=O)[C@@]4(CCOc5c4cc(c(c5)Cl)Cl)NC3=O | −8.4 ± 0.1 | 6.14 ± 0.09 |
| 22 | VLA-UNK-3a43cd95-3 |
|
c1ccc2c(c1)cncc2N3C(=O)C[C@@]4(C3=O)CCOc5c4cc(c(c5)F)Cl | −8.4 ± 0.2 | 6.1 ± 0.1 |
| 23 | EDJ-MED-a6bab6fb-1 |
|
Cc1cccc2c1c(cnc2)N3CCC4(C3)CCOc5c4cc(cc5)Cl | −8.1 ± 0.1 | 5.93 ± 0.10 |
| 24 | VLA-UNK-56836b69-3 |
|
CN1C(=O)N(C(=O)[C@@]12CCOc3c2cc(c(c3)Cl)Cl)c4cncc5c4cccc5 | −8.1 ± 0.1 | 5.9 ± 0.1 |
| 25 | ALP-POS-4483ae88-1 |
|
c1ccc2c(c1)cncc2N3CCC4(C3=O)CNS(=O)(=O)c5c4cc(cc5)Cl | −8.1 ± 0.2 | 5.9 ± 0.1 |
| 26 | EDJ-MED-e78d5f1a-1 |
|
c1cc2cncc(c2c(c1)Cl)N3CCC4(C3)CCOc5c4cc(cc5)Cl | −7.9 ± 0.1 | 5.79 ± 0.09 |
| 27 | EDJ-MED-159244ea-2 |
|
c1ccc2c(c1)cncc2N3CC[C@@]4(C3)CCOc5c4cc(cc5)Cl | −7.6 ± 0.1 | 5.57 ± 0.09 |
| 28 | ALP-POS-41e2080f-1 |
|
c1ccc2c(c1)cncc2N3CCC4(C3=O)CCS(=O)(=O)c5c4cc(cc5)Cl | −7.6 ± 0.2 | 5.6 ± 0.1 |
| 29 | EDJ-MED-d4864bdc-3 |
|
c1ccc2c(c1)cncc2N3CCC4(C3=O)CCS(=O)(=O)c5c4cc(cc5)Cl | −7.4 ± 0.2 | 5.4 ± 0.1 |
| 30 | MAT-POS-983b399a-2 |
|
c1ccc2c(c1)cncc2N3CCC4(C3)CCOc5c4cc(cc5)Cl | −7.0 ± 0.2 | 5.1 ± 0.1 |
| 31 | BRU-THA-55eab31a-1 |
|
c1ccc2c(c1)cncc2N3C(=O)C4(CCNc5c4cc(cc5)Cl)C=N3 | −6.4 ± 0.2 | 4.7 ± 0.1 |
| 32 | EDJ-MED-159244ea-3 |
|
c1ccc2c(c1)cncc2N3C[C@@]4(CCOc5c4cc(cc5)Cl)CC3=O | −6.1 ± 0.1 | 4.44 ± 0.08 |
| 33 | MAT-POS-983b399a-3 |
|
c1ccc2c(c1)cncc2N3CC4(CCOc5c4cc(cc5)Cl)CC3=O | −5.5 ± 0.1 | 4.01 ± 0.09 |
| 34 | EDJ-MED-f3cfbbb5-1 |
|
Cc1cccc2c1c(cnc2)N3CCC4(C3)COCc5c4cc(cc5)Cl | −5.1 ± 0.2 | 3.8 ± 0.1 |