COVID Moonshot Sprint 5 to prioritize benzopyran-isoquinoline series based on x11498 (MAT-POS-b3e365b9-1) to optimize substituents in the P1' pocket with Mpro monomer and neutral Cys145:His41
Rank | Compound | SMILES | ΔG / kcal mol-1 | pIC50 | |
---|---|---|---|---|---|
1 | DAR-DIA-5ff57136-12 | c1ccc2c(c1)cncc2N(C#CC3CCCN3)C(=O)[C@@H]4CCOc5c4cc(cc5)Cl | −12.6 ± 0.2 | 9.2 ± 0.2 | |
2 | DAR-DIA-5ff57136-13 | C#CCN(c1cncc2c1cccc2)C(=O)[C@@H]3CCOc4c3cc(cc4)Cl | −12.5 ± 0.1 | 9.09 ± 0.10 | |
3 | EDJ-MED-28ec730d-5 | c1ccc2c(c1)cncc2NC(=O)[C@@]3(CCOc4c3cc(cc4)Cl)OCCc5c[nH]nc5 | −12.4 ± 0.2 | 9.0 ± 0.2 | |
4 | VLA-UCB-34f3ed0c-8 | c1ccc2c(c1)cncc2NC(=O)[C@@]3(CCOc4c3cc(cc4)Cl)C(=O)CCc5cc[nH]n5 | −12.4 ± 0.2 | 9.0 ± 0.2 | |
5 | VLA-UCB-34f3ed0c-9 | c1ccc2c(c1)cncc2NC(=O)[C@@]3(CCOc4c3cc(cc4)Cl)C(=O)CCc5c[nH]c(=O)o5 | −12.3 ± 0.3 | 9.0 ± 0.2 | |
6 | VLA-UCB-34f3ed0c-21 | c1ccc2c(c1)cncc2NC(=O)[C@@]3(CCOc4c3cc(cc4)Cl)C(=O)CCC5CC(=O)NC5 | −12.3 ± 0.3 | 8.9 ± 0.2 | |
7 | MAK-UNK-8be7dca9-6 | c1cc(c2cncc(c2c1)NC(=O)C3CCOc4c3cc(cc4)Cl)CN | −12.03 ± 0.10 | 8.76 ± 0.07 | |
8 | MAK-UNK-3875bbc8-2 | CN(c1cncc2c1cccc2)C(=O)C3CCOc4c3cc(cc4)Cl | −11.97 ± 0.08 | 8.72 ± 0.06 | |
9 | DAR-DIA-5ff57136-17 | c1ccc2c(c1)cncc2N(CC#CBr)C(=O)[C@@H]3CCOc4c3cc(cc4)Cl | −11.9 ± 0.2 | 8.7 ± 0.1 | |
10 | NAU-LAT-b7d8c353-8 | c1cc(c2cncc(c2c1)NC(=O)C3CCOc4c3cc(cc4)Cl)CN | −11.92 ± 0.10 | 8.68 ± 0.07 | |
11 | JOH-SUS-a69c159d-6 | c1ccc2c(c1)c(c(nc2F)F)NC(=O)C3CCOc4c3cc(cc4)Cl | −11.88 ± 0.06 | 8.66 ± 0.04 | |
12 | JOH-SUS-a69c159d-7 | c1cc2c(cc1F)c(c(nc2F)F)NC(=O)C3CCOc4c3cc(cc4)Cl | −11.83 ± 0.06 | 8.62 ± 0.04 | |
13 | EDJ-MED-e4b030d8-6 | CCC[C@H]1COc2ccc(cc2[C@@H]1C(=O)Nc3cncc4c3cccc4)Cl | −11.5 ± 0.1 | 8.38 ± 0.08 | |
14 | EDJ-MED-28ec730d-2 | COCC[C@]1(CCOc2c1cc(cc2)Cl)C(=O)Nc3cncc4c3cccc4 | −11.4 ± 0.2 | 8.3 ± 0.1 | |
15 | DAR-DIA-0d514e7d-4 | C[C@H]1COc2c(cc(cc2OC3CCCC3)Cl)[C@@H]1C(=O)Nc4cncc5c4cccc5 | −11.4 ± 0.2 | 8.3 ± 0.2 | |
16 | VLA-UCB-50c39ae8-1 | CC(=O)N(c1cncc2c1cccc2)C(=O)[C@@H]3CCOc4c3cc(cc4)Cl | −11.3 ± 0.2 | 8.2 ± 0.1 | |
17 | DAR-DIA-0d514e7d-28 | C[C@H]1COc2ccc(cc2[C@]1(C)C(=O)Nc3cncc4c3cccc4)Cl | −11.13 ± 0.10 | 8.11 ± 0.07 | |
18 | MAK-UNK-8be7dca9-1 | c1cc2c(cc1CN3CCNCC3)cncc2NC(=O)C4CCOc5c4cc(cc5)Cl | −11.1 ± 0.1 | 8.08 ± 0.09 | |
19 | EDJ-MED-28ec730d-4 | c1ccc2c(c1)cncc2NC(=O)[C@@]3(CCOc4c3cc(cc4)Cl)OCc5c[nH]nc5 | −11.1 ± 0.2 | 8.1 ± 0.2 | |
20 | MAK-UNK-83e0a0b4-2 | c1cc2c(cc1CN3CCNCC3)cncc2N(CCNC4CNC4)C(=O)C5CCOc6c5cc(cc6)Cl | −11.0 ± 0.3 | 8.0 ± 0.2 | |
21 | MAK-UNK-3875bbc8-1 | Cc1ccc2c(c1)C(CCO2)C(=O)N(C)c3cncc4c3cccc4 | −10.96 ± 0.09 | 7.98 ± 0.07 | |
22 | BEN-BAS-5c03e89e-1 | CC(C)(C1COc2ccc(cc2C1C(=O)Nc3cncc4c3cccc4)Cl)O | −10.9 ± 0.1 | 7.96 ± 0.07 | |
23 | PET-UNK-29afea89-1 | C#C[C@]1(CCOc2c1cc(cc2)Cl)C(=O)Nc3cncc4c3cccc4 | −10.9 ± 0.1 | 7.94 ± 0.08 | |
24 | JOH-SUS-a69c159d-5 | c1cc2c(cc1F)c(cnc2F)NC(=O)C3CCOc4c3cc(cc4)Cl | −10.82 ± 0.05 | 7.88 ± 0.04 | |
25 | ADA-UCB-dc2b944c-16 | CC1(C[C@H](c2cc(ccc2O1)Cl)C(=O)Nc3cncc4c3cccc4)C | −10.7 ± 0.1 | 7.83 ± 0.08 | |
26 | JOH-SUS-a69c159d-2 | c1ccc2c(c1)c(cnc2F)NC(=O)C3CCOc4c3cc(cc4)Cl | −10.73 ± 0.05 | 7.82 ± 0.04 | |
27 | MAK-UNK-8be7dca9-5 | c1cc2c(cc1CN)cncc2NC(=O)C3CCOc4c3cc(cc4)Cl | −10.71 ± 0.09 | 7.80 ± 0.07 | |
28 | ALP-POS-d3acb8cc-1 | C[C@H]1C[C@H](c2cc(ccc2O1)Cl)C(=O)Nc3cncc4c3cccc4 | −10.69 ± 0.09 | 7.79 ± 0.06 | |
29 | DAR-DIA-6a508060-10 | CC1(CCOc2c1cc(cc2)Cl)C(=O)Nc3cncc4c3cccc4 | −10.7 ± 0.1 | 7.77 ± 0.08 | |
30 | JOH-UNI-f51e3bbc-4 | COc1c(c2ccccc2cn1)NC(=O)C3CCOc4c3cc(cc4)Cl | −10.7 ± 0.1 | 7.8 ± 0.1 | |
31 | MAK-UNK-8be7dca9-4 | c1cc2cncc(c2cc1N3CCNCC3)NC(=O)C4CCOc5c4cc(cc5)Cl | −10.65 ± 0.09 | 7.76 ± 0.06 | |
32 | MAT-POS-8a69d52e-4 | CC1COc2ccc(cc2C1C(=O)Nc3cncc4c3cccc4)Cl | −10.65 ± 0.06 | 7.75 ± 0.04 | |
33 | DAR-DIA-0d514e7d-8 | C[C@H]1COc2ccc(cc2[C@@H]1C(=O)Nc3cncc4c3cccc4)C#N | −10.60 ± 0.08 | 7.72 ± 0.06 | |
34 | DAR-DIA-0d514e7d-25 | C[C@H]1COc2c(cc(cc2OC)Cl)[C@]1(C)C(=O)Nc3cncc4c3cccc4 | −10.6 ± 0.1 | 7.70 ± 0.10 | |
35 | JAG-UCB-706446eb-4 | CCOC(=O)CC[C@]1(CCOc2c1cc(cc2)Cl)C(=O)Nc3cncc4c3cccc4 | −10.6 ± 0.2 | 7.7 ± 0.2 | |
36 | MAK-UNK-8be7dca9-7 | c1cc2cncc(c2cc1C(=O)O)NC(=O)C3CCOc4c3cc(cc4)Cl | −10.41 ± 0.09 | 7.58 ± 0.06 | |
37 | MAT-POS-8a69d52e-1 | CC1CC(c2cc(ccc2O1)Cl)C(=O)Nc3cncc4c3cccc4 | −10.34 ± 0.08 | 7.53 ± 0.06 | |
38 | DAR-DIA-0d514e7d-1 | C[C@H]1COc2c(cc(cc2OC)Cl)[C@@H]1C(=O)Nc3cncc4c3cccc4 | −10.3 ± 0.1 | 7.50 ± 0.09 | |
39 | BEN-DND-c852c98b-4 | c1cc2cncc(c2cc1O)NC(=O)C3CCOc4c3cc(cc4)Cl | −10.28 ± 0.05 | 7.49 ± 0.04 | |
40 | EDJ-MED-e4b030d8-11 | C[C@H]1COc2ccc(cc2[C@@H]1C(=O)Nc3cncc4c3cccc4)Cl | −10.25 ± 0.06 | 7.47 ± 0.04 | |
41 | BEN-DND-c852c98b-1 | c1cc2cncc(c2cc1C#N)NC(=O)C3CCOc4c3cc(cc4)Cl | −10.23 ± 0.05 | 7.45 ± 0.04 | |
42 | PET-UNK-29afea89-2 | CO[C@]1(CCOc2c1cc(cc2)Cl)C(=O)Nc3cncc4c3cccc4 | −10.2 ± 0.1 | 7.43 ± 0.10 | |
43 | DAR-DIA-6a508060-3 | c1ccc2c(c1)cncc2NC(=O)C3CCOc4c3cc(cc4)C#N | −10.14 ± 0.07 | 7.39 ± 0.05 | |
44 | DAR-DIA-23e5a6a0-2 | c1ccc2c(c1)cncc2NC(=O)[C@@H]3CCOc4c3cc(cc4OC5CC6(N5)CCC6)Cl | −10.0 ± 0.3 | 7.3 ± 0.2 | |
45 | ALP-POS-696356e4-1 | c1cc2cncc(c2cc1F)NC(=O)C3CCOc4c3cc(cc4)Cl | −9.91 ± 0.05 | 7.22 ± 0.04 | |
46 | BEN-DND-c852c98b-6 | c1cc2cncc(c2cc1OC(F)F)NC(=O)C3CCOc4c3cc(cc4)Cl | −9.90 ± 0.07 | 7.21 ± 0.05 | |
47 | BEN-DND-c852c98b-5 | CS(=O)(=O)c1ccc2cncc(c2c1)NC(=O)C3CCOc4c3cc(cc4)Cl | −9.89 ± 0.09 | 7.20 ± 0.06 | |
48 | MAK-UNK-8be7dca9-2 | c1cc2c(cc1CC(=O)N)cncc2NC(=O)C3CCOc4c3cc(cc4)Cl | −9.84 ± 0.09 | 7.17 ± 0.07 | |
49 | ALP-POS-d3acb8cc-4 | C[C@@H]1C[C@H](c2cc(ccc2O1)Cl)C(=O)Nc3cncc4c3cccc4 | −9.80 ± 0.06 | 7.14 ± 0.04 | |
50 | NAU-LAT-0543f7f2-10 | CC(=O)NCCOc1cc(cc2c1OCCC2C(=O)Nc3cncc4c3cccc4)Cl | −9.8 ± 0.3 | 7.1 ± 0.2 | |
51 | EDJ-MED-e4b030d8-2 | C[C@@H]1C[C@H](c2cc(ccc2O1)Cl)C(=O)Nc3cncc4c3cccc4 | −9.78 ± 0.05 | 7.12 ± 0.04 | |
52 | EDJ-MED-e4b030d8-13 | C[C@]1(CCOc2c1cc(cc2)Cl)C(=O)Nc3cncc4c3cccc4 | −9.77 ± 0.07 | 7.11 ± 0.05 | |
53 | MAT-POS-b3e365b9-1 | c1ccc2c(c1)cncc2NC(=O)[C@@H]3CCOc4c3cc(cc4)Cl | −9.75 ± 0.04 | 7.11 ± 0.03 | |
54 | MAT-POS-f7918075-1 | c1ccc2c(c1)cncc2NC(=O)C3CCOc4c3cc(cc4)Cl | −9.74 ± 0.05 | 7.10 ± 0.03 | |
55 | VLA-UCB-1dbca3b4-15 | c1ccc2c(c1)cncc2NC(=O)C3CCOc4c3cc(cc4)Cl | −9.71 ± 0.04 | 7.07 ± 0.03 | |
56 | DAR-DIA-0d514e7d-29 | C[C@@H]1COc2ccc(cc2[C@]1(C)C(=O)Nc3cncc4c3cccc4)Cl | −9.7 ± 0.2 | 7.1 ± 0.1 | |
57 | EDJ-MED-e4b030d8-7 | COc1cc(cc2c1OCC[C@H]2C(=O)Nc3cncc4c3cccc4)Cl | −9.7 ± 0.1 | 7.0 ± 0.1 | |
58 | BEN-DND-c852c98b-7 | c1cc2cncc(c2cc1C(F)F)NC(=O)C3CCOc4c3cc(cc4)Cl | −9.58 ± 0.06 | 6.98 ± 0.05 | |
59 | DAR-DIA-23e5a6a0-3 | c1ccc2c(c1)cncc2NC(=O)[C@@H]3CCOc4c3cc(cc4OC5CC6(N5)COC6)Cl | −9.6 ± 0.5 | 7.0 ± 0.4 | |
60 | ADA-UCB-dc2b944c-11 | c1ccc2c(c1)c(cnc2Br)NC(=O)[C@@H]3CCOc4c3cc(cc4)Cl | −9.56 ± 0.08 | 6.96 ± 0.06 | |
61 | BEN-DND-c852c98b-2 | c1cc2cncc(c2cc1OC(F)(F)F)NC(=O)C3CCOc4c3cc(cc4)Cl | −9.52 ± 0.07 | 6.94 ± 0.05 | |
62 | VLA-UCB-05e51b3f-13 | c1ccc2c(c1)cncc2NC(=O)[C@]3(CCOc4c3cc(cc4)Cl)CCC5CCCCC5 | −9.5 ± 0.3 | 6.9 ± 0.2 | |
63 | MAT-POS-11b63608-1 | c1ccc2c(c1)cncc2NC(=O)C3CCOc4c3cc(cc4)Br | −9.43 ± 0.06 | 6.87 ± 0.04 | |
64 | EDJ-MED-e4b030d8-10 | c1ccc2c(c1)cncc2NC(=O)[C@@H]3CCOc4c3c(c(cc4)Cl)Cl | −9.4 ± 0.1 | 6.86 ± 0.08 | |
65 | DAR-DIA-6a508060-4 | COc1cc(cc2c1OCCC2C(=O)Nc3cncc4c3cccc4)Cl | −9.4 ± 0.1 | 6.85 ± 0.08 | |
66 | ADA-UCB-dc2b944c-10 | Cc1c(c2ccccc2cn1)NC(=O)[C@@H]3CCOc4c3cc(cc4)Cl | −9.4 ± 0.1 | 6.83 ± 0.07 | |
67 | MAK-UNK-8be7dca9-9 | c1cc2c(cc1C(=O)O)cncc2NC(=O)C3CCOc4c3cc(cc4)Cl | −9.16 ± 0.07 | 6.67 ± 0.05 | |
68 | EDJ-MED-e4b030d8-1 | C[C@@]1(c2cc(ccc2OCC1=O)Cl)C(=O)Nc3cncc4c3cccc4 | −9.1 ± 0.1 | 6.64 ± 0.08 | |
69 | MAK-UNK-8be7dca9-8 | c1cc2cncc(c2cc1CC(=O)O)NC(=O)C3CCOc4c3cc(cc4)Cl | −9.10 ± 0.08 | 6.63 ± 0.06 | |
70 | DAR-DIA-6a508060-8 | c1ccc2c(c1)cncc2NC(=O)C3CCOc4c3cc(cc4)C5CC5 | −9.0 ± 0.1 | 6.59 ± 0.08 | |
71 | ADA-UCB-dc2b944c-9 | c1ccc2c(c1)cnc(c2NC(=O)[C@@H]3CCOc4c3cc(cc4)Cl)Br | −9.0 ± 0.1 | 6.56 ± 0.09 | |
72 | DAR-DIA-23e5a6a0-5 | c1ccc2c(c1)cncc2NC(=O)[C@@H]3CCOc4c3cc(cc4OC5CC6(N5)CC6)Cl | −9.0 ± 0.3 | 6.5 ± 0.2 | |
73 | ADA-UCB-dc2b944c-12 | Cc1c2ccccc2c(cn1)NC(=O)[C@@H]3CCOc4c3cc(cc4)Cl | −8.94 ± 0.07 | 6.51 ± 0.05 | |
74 | DAR-DIA-6a508060-9 | c1ccc2c(c1)cncc2NC(=O)C3(CCOc4c3cc(cc4)Cl)CCC5CCCCC5 | −8.9 ± 0.3 | 6.5 ± 0.2 | |
75 | VLA-UCB-1dbca3b4-14 | CC1(c2cc(ccc2OCC1=O)Cl)C(=O)Nc3cncc4c3cccc4 | −8.9 ± 0.1 | 6.49 ± 0.08 | |
76 | BEN-DND-c852c98b-3 | CC(C)(c1ccc2cncc(c2c1)NC(=O)C3CCOc4c3cc(cc4)Cl)O | −8.90 ± 0.09 | 6.48 ± 0.06 | |
77 | EDJ-MED-e4b030d8-8 | Cc1c(ccc2c1[C@@H](CCO2)C(=O)Nc3cncc4c3cccc4)Cl | −8.78 ± 0.07 | 6.40 ± 0.05 | |
78 | ADA-UCB-dc2b944c-7 | c1ccc2c(c1)cncc2NC(=O)[C@@H]3CCOc4c3cc(cc4)F | −8.77 ± 0.07 | 6.39 ± 0.05 | |
79 | ADA-UCB-dc2b944c-5 | Cc1ccc2c(c1)[C@@H](CCO2)C(=O)Nc3cncc4c3cccc4 | −8.75 ± 0.06 | 6.37 ± 0.05 | |
80 | JOH-SUS-a69c159d-1 | Cc1c2ccccc2c(cn1)NC(=O)C3CCOc4c3cc(cc4)Cl | −8.69 ± 0.06 | 6.33 ± 0.05 | |
81 | EDJ-MED-e4b030d8-3 | C[C@H]1C[C@H](c2cc(ccc2O1)Cl)C(=O)Nc3cncc4c3cccc4 | −8.69 ± 0.07 | 6.33 ± 0.05 | |
82 | DAR-DIA-6a508060-13 | CS(=O)(=O)NCCC1(CCOc2c1cc(cc2)Cl)C(=O)Nc3cncc4c3cccc4 | −8.6 ± 0.3 | 6.3 ± 0.2 | |
83 | MAK-UNK-8be7dca9-3 | c1ccc2c(c1)cncc2NC(=O)C3c4cc(ccc4OCC3CN)Cl | −8.5 ± 0.1 | 6.19 ± 0.09 | |
84 | ADA-UCB-dc2b944c-8 | c1cc2c(cncc2NC(=O)[C@@H]3CCOc4c3cc(cc4)Cl)c(c1)Cl | −8.48 ± 0.06 | 6.18 ± 0.04 | |
85 | MAK-UNK-8be7dca9-10 | c1ccc2c(c1)cncc2NC(=O)C3CC(Oc4c3cc(cc4)Cl)C(=O)O | −7.89 ± 0.08 | 5.74 ± 0.06 | |
86 | ALP-UNI-4b8a177c-1 | c1ccc2c(c1)cncc2NC(=O)C3CCOc4c3c(ccc4O)Cl | −7.7 ± 0.2 | 5.6 ± 0.1 | |
87 | EDJ-MED-28ec730d-1 | COCCC[C@]1(CCOc2c1cc(cc2)Cl)C(=O)Nc3cncc4c3cccc4 | −7.5 ± 0.2 | 5.5 ± 0.2 | |
88 | JOH-UNI-f51e3bbc-3 | c1ccc2c(c1)cnc(c2NC(=O)C3CCOc4c3cc(cc4)Cl)O | −7.4 ± 0.2 | 5.4 ± 0.1 | |
89 | ALP-POS-477dc5b7-3 | c1ccc2c(c1)cncc2NC(=O)C3(CCOc4c3cc(cc4)Cl)CCC5CC5 | −6.87 ± 0.09 | 5.00 ± 0.07 | |
90 | JAG-UCB-706446eb-3 | c1ccc2c(c1)cncc2NC(=O)[C@@]3(CCOc4c3cc(cc4)Cl)CCC(=O)O | −6.5 ± 0.2 | 4.8 ± 0.2 | |
91 | JOH-SUS-a69c159d-3 | c1ccc2c(c1)c(cnc2C(F)F)NC(=O)C3CCOc4c3cc(cc4)Cl | −5.9 ± 0.2 | 4.3 ± 0.1 |