Description

COVID Moonshot Sprint 10 for P1 pocket replacement based on x10959 (ADA-UCB-6c2cb422-1) to optimize substituents in the P1 pocket with Mpro dimer and neutral Cys145:His41 catalytic dyad

Progress

100.00%

Distributions

relative free energy distribution cumulative free energy distribution

Leaderboard

Rank Compound SMILES ΔG / kcal mol-1 pIC50
1 DAR-DIA-56cf811e-1 molecule C#CC(=O)N(c1cncc2c1cccc2)C(=O)Cc3cccc(c3)Cl −13.9 ± 0.1 10.1 ± 0.1
2 TRY-UNI-9f475305-8 molecule Cc1cc(no1)CN(C(=O)C(C)c2cccc(c2)Cl)C(=O)NC3CC3 −13.5 ± 0.2 9.9 ± 0.1
3 PET-UNK-12d8d43f-2 molecule COC(=O)N(c1cncc2c1cccc2)C(=O)Cc3cccc(c3)Cl −12.7 ± 0.2 9.2 ± 0.1
4 JOH-UNI-a38a7bdd-7 molecule Cc1ccncc1N(C(=O)Cc2cccc(c2)Cl)C(=O)C3CC3C(F)(F)F −10.8 ± 0.1 7.9 ± 0.1
5 EDJ-MED-c8e7a002-17 molecule c1cc(cc(c1)Cl)CC(=O)Nc2c3nnc(n3cnc2Cl)O −10.5 ± 0.1 7.66 ± 0.07
6 BAR-COM-0f94fc3d-24 molecule c1ccc2c(c1)ncn2NC(=O)C(c3cccc(c3)Cl)(F)F −10.4 ± 0.1 7.55 ± 0.08
7 EDJ-MED-ee07cf00-13 molecule Cc1nc2n(n1)C[C@@H](CC2)C(=O)NC(c3cccc(c3)Cl)C(=O)Nc4cncc5c4cccc5 −10.3 ± 0.2 7.5 ± 0.1
8 EDJ-MED-c8e7a002-8 molecule c1cc(cc(c1)Cl)CC(=O)Nc2c3nnnn3cnc2Cl −9.8 ± 0.1 7.17 ± 0.10
9 RUB-POS-1325a9ea-18 molecule c1ccc2c(c1)cnc(c2NC(=O)Cc3cccc(c3)Cl)F −9.82 ± 0.03 7.16 ± 0.02
10 PET-UNK-1320d94d-9 molecule c1ccc2c(c1)cncc2NC(=O)[C@@H](c3cccc(c3)Cl)NC(=O)[C@@H]4CCC[C@@H](O4)C(=O)N5CCCC5 −9.7 ± 0.2 7.0 ± 0.2
11 EDJ-MED-c8e7a002-1 molecule COc1ccc2c(c1)onc2NC(=O)Cc3cccc(c3)Cl −9.6 ± 0.1 7.02 ± 0.09
12 PET-UNK-ac320b15-7 molecule c1ccc2c(c1)cncc2NC(=O)[C@@H](c3cccc(c3)Cl)NC(=O)[C@@H]4CC[C@H](O4)C(=O)N5CCCC5 −9.6 ± 0.2 7.0 ± 0.1
13 EDJ-MED-076d6e64-1 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncn3c2nnc3 −9.6 ± 0.1 6.96 ± 0.08
14 BAR-COM-ebf5acce-14 molecule Cc1ccncc1N(CCn2cccn2)C(=O)Cc3cccc(c3)Cl −9.5 ± 0.2 7.0 ± 0.1
15 JAN-GHE-5a013bed-9 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncnc2 −9.5 ± 0.1 6.93 ± 0.09
16 PET-UNK-1320d94d-21 molecule CN(C)C(=O)[C@H]1CC[C@H](O1)C(=O)N(C)[C@H](c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −9.5 ± 0.2 6.9 ± 0.2
17 JAN-GHE-83b26c96-7 molecule Cc1c(cncn1)NC(=O)C(c2cccc(c2)Cl)C(C)C −9.4 ± 0.2 6.9 ± 0.1
18 MIC-UNK-c66144cb-3 molecule c1ccc2c(c1)cncc2NC(=O)C(CCC3CCCCC3)c4cccc(c4)Cl −9.4 ± 0.2 6.9 ± 0.2
19 VLA-UNK-dc1d9354-1 molecule c1ccc2c(c1)[nH]c(=O)n2NC(=O)Cc3cccc(c3)Cl −9.4 ± 0.1 6.8 ± 0.1
20 PET-UNK-1320d94d-29 molecule CN([C@H](c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3)C(=O)[C@@H]4CCC[C@@H](O4)C(=O)N5CCCC5 −9.2 ± 0.2 6.7 ± 0.2
21 JAN-GHE-5a013bed-4 molecule c1cc(cc(c1)Cl)CC(=O)Nn2cn[nH]c2=O −9.2 ± 0.1 6.70 ± 0.09
22 ALP-POS-3b848b35-4 molecule c1ccc2c(c1)cncc2NC(=O)C(CCC3CCCCC3)c4cccc(c4)Cl −9.2 ± 0.2 6.7 ± 0.1
23 VLA-UNK-411a133b-1 molecule Cn1nc(nn1)NC(=O)Cc2cccc(c2)Cl −9.2 ± 0.1 6.68 ± 0.08
24 JAN-GHE-f4ca5a00-20 molecule CCCCC(c1cccc(c1)Cl)C(=O)Nn2c(cnn2)C3CC3 −9.1 ± 0.2 6.6 ± 0.1
25 PET-UNK-1320d94d-1 molecule CN(C)C(=O)[C@H]1CC[C@H](O1)C(=O)N[C@H](c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −9.1 ± 0.2 6.6 ± 0.1
26 MAT-POS-bfb445d4-2 molecule c1ccc2c(c1)nnn2NC(=O)Cc3cccc(c3)Cl −9.11 ± 0.07 6.63 ± 0.05
27 MIC-UNK-5a93dd5f-12 molecule c1ccc2c(c1)cncc2NC(=O)C(c3cccc(c3)Cl)N4CCC(C4)N5CCCCC5 −9.1 ± 0.1 6.62 ± 0.08
28 MIC-UNK-d36ab305-4 molecule CN(C)c1ccc(cc1)C(c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −9.1 ± 0.2 6.6 ± 0.1
29 DAR-DIA-076fb6ea-6 molecule Cc1ccncc1N(C#CC#N)C(=O)Cc2cccc(c2)Cl −9.0 ± 0.2 6.6 ± 0.1
30 JAN-GHE-f4ca5a00-18 molecule CCCCC(c1cccc(c1)Cl)C(=O)Nn2cncc2C3CC3 −9.0 ± 0.2 6.6 ± 0.1
31 MIC-UNK-c66144cb-1 molecule c1ccc2c(c1)cncc2NC(=O)C(CCc3cccc(c3)F)c4cccc(c4)Cl −8.9 ± 0.2 6.5 ± 0.2
32 PET-UNK-ac320b15-5 molecule c1ccc2c(c1)cncc2NC(=O)[C@@H](c3cccc(c3)Cl)NC(=O)[C@H]4CC[C@@H](O4)C(=O)N5CCCC5 −8.9 ± 0.2 6.5 ± 0.2
33 EDJ-MED-c8e7a002-13 molecule c1cc(cc(c1)Cl)CC(=O)Nc2c3c(cccc3F)n[nH]2 −8.9 ± 0.1 6.46 ± 0.10
34 PET-UNK-1320d94d-25 molecule CN([C@H](c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3)C(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCC5 −8.9 ± 0.2 6.5 ± 0.1
35 JOH-UNI-a38a7bdd-3 molecule Cc1ccncc1N(C(=O)Cc2cccc(c2)Cl)C(=O)C(F)(F)F −8.8 ± 0.2 6.4 ± 0.1
36 PET-UNK-1320d94d-5 molecule c1ccc2c(c1)cncc2NC(=O)[C@@H](c3cccc(c3)Cl)NC(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCC5 −8.8 ± 0.2 6.4 ± 0.1
37 PET-UNK-6314f867-3 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncc3c2c(ccc3)C#N −8.8 ± 0.1 6.43 ± 0.09
38 TRY-UNI-9f475305-3 molecule Cc1ccncc1NC(=O)C(c2cccc(c2)Cl)c3nnc(s3)C −8.8 ± 0.1 6.42 ± 0.08
39 MAT-POS-bb423b95-8 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncc3c2ccc(c3)O −8.8 ± 0.1 6.42 ± 0.09
40 MIC-UNK-c66144cb-2 molecule c1ccc2c(c1)cncc2NC(=O)C(CCc3ccc(cc3)F)c4cccc(c4)Cl −8.8 ± 0.2 6.4 ± 0.1
41 SAM-UNK-2684b532-3 molecule Cc1ccncc1NC(=O)C(c2cccc(c2)Cl)c3nnc(s3)C −8.8 ± 0.1 6.40 ± 0.08
42 PET-UNK-1320d94d-3 molecule c1ccc2c(c1)cncc2NC(=O)[C@@H](c3cccc(c3)Cl)NC(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCOCC5 −8.8 ± 0.2 6.4 ± 0.2
43 EDJ-MED-97c1bf5c-2 molecule COc1c(c2nnnn2cn1)NC(=O)Cc3cccc(c3)Cl −8.8 ± 0.1 6.39 ± 0.10
44 PET-UNK-5ecb6237-1 molecule c1ccc2c(c1)cncc2N(C#N)C(=O)Cc3cccc(c3)Cl −8.8 ± 0.2 6.4 ± 0.1
45 DAR-DIA-076fb6ea-3 molecule COC(=O)/C=C/C(=O)N(c1cncc2c1cccc2)C(=O)Cc3cccc(c3)Cl −8.7 ± 0.2 6.3 ± 0.2
46 JAN-GHE-83b26c96-15 molecule Cc1ccncc1N(C)C(=O)Cc2cccc(c2)Cl −8.7 ± 0.2 6.3 ± 0.1
47 DAR-DIA-076fb6ea-7 molecule Cc1ccncc1N(C(=O)Cc2cccc(c2)Cl)C(=O)C=C=C −8.7 ± 0.2 6.3 ± 0.1
48 EDJ-MED-ee07cf00-11 molecule c1ccc2c(c1)cncc2NC(=O)C(c3cccc(c3)Cl)NC(=O)C4CCC(O4)C(=O)N5CCCC5 −8.6 ± 0.1 6.30 ± 0.08
49 PET-UNK-6314f867-2 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncc3c2ccc(c3)C#N −8.6 ± 0.2 6.2 ± 0.1
50 JIN-POS-6dc588a4-16 molecule c1cc(cc(c1)Cl)CC(=O)Nc2c3ccncc3on2 −8.5 ± 0.1 6.23 ± 0.08
51 PET-UNK-b38839dc-2 molecule COc1cc2c(cc1Cl)cncc2NC(=O)Cc3cccc(c3)Cl −8.5 ± 0.1 6.2 ± 0.1
52 PET-UNK-ac320b15-9 molecule c1ccc2c(c1)cncc2NC(=O)[C@@H](c3cccc(c3)Cl)NC(=O)[C@H]4CC[C@H](O4)C(=O)N5CCCC5 −8.5 ± 0.2 6.2 ± 0.1
53 VLA-UNK-9a7dc93f-7 molecule COC(c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3 −8.51 ± 0.05 6.20 ± 0.03
54 ROB-UNI-daaf9793-3 molecule c1ccc2c(c1)CC(=CC2=O)NC(=O)Cc3cccc(c3)Cl −8.5 ± 0.1 6.2 ± 0.1
55 JIN-POS-6dc588a4-17 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cc3nccn3cn2 −8.5 ± 0.2 6.2 ± 0.1
56 PET-UNK-1320d94d-7 molecule c1ccc2c(c1)cncc2NC(=O)[C@@H](c3cccc(c3)Cl)NC(=O)[C@@H]4C[C@@H](O4)C(=O)N5CCCC5 −8.5 ± 0.2 6.2 ± 0.2
57 JAN-GHE-5a013bed-2 molecule c1ccc2c(c1)ncn2NC(=O)Cc3cccc(c3)Cl −8.41 ± 0.07 6.13 ± 0.05
58 EDJ-MED-ee07cf00-2 molecule Cc1c(c(=O)n2c(n1)cc[nH]2)CC(=O)NC(c3cccc(c3)Cl)C(=O)Nc4cncc5c4cccc5 −8.4 ± 0.2 6.1 ± 0.1
59 MAT-POS-a13804f0-4 molecule c1ccc2c(c1)cncc2NC(=O)C(c3cccc(c3)Cl)NC(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCCC5 −8.35 ± 0.07 6.09 ± 0.05
60 JAN-GHE-f4ca5a00-17 molecule c1cc(cc(c1)Cl)CC(=O)Nn2c(cnn2)C3CC3 −8.4 ± 0.1 6.09 ± 0.08
61 MIC-UNK-5a93dd5f-3 molecule c1ccc2c(c1)cncc2NC(=O)C(c3cccc(c3)Cl)N4CCC5CCCCC5C4 −8.35 ± 0.08 6.08 ± 0.06
62 PET-UNK-10339a1d-1 molecule CN(C(c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3)C(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCCC5 −8.3 ± 0.2 6.1 ± 0.1
63 JOH-UNI-ee5ed7c8-6 molecule c1ccc2c(c1)cncc2NC(=O)C(CC#N)c3cccc(c3)Cl −8.3 ± 0.1 6.07 ± 0.07
64 PET-UNK-1320d94d-30 molecule CN([C@@H](c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3)C(=O)[C@@H]4CCC[C@@H](O4)C(=O)N5CCCC5 −8.3 ± 0.2 6.1 ± 0.1
65 MIC-UNK-5a93dd5f-2 molecule c1ccc2c(c1)cncc2NC(=O)C(c3cccc(c3)Cl)N4CC5CCCCC5C4 −8.3 ± 0.2 6.1 ± 0.1
66 MIC-UNK-d36ab305-1 molecule CC(=O)Nc1ccc(cc1)C(c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −8.3 ± 0.1 6.06 ± 0.10
67 EDJ-MED-c8e7a002-7 molecule c1cc(cc(c1)Cl)CC(=O)Nc2c3nncn3cnc2Cl −8.3 ± 0.1 6.0 ± 0.1
68 MAT-POS-f7918075-3 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncc3c2cccn3 −8.29 ± 0.04 6.04 ± 0.03
69 PET-UNK-1320d94d-10 molecule c1ccc2c(c1)cncc2NC(=O)[C@H](c3cccc(c3)Cl)NC(=O)[C@@H]4CCC[C@@H](O4)C(=O)N5CCCC5 −8.2 ± 0.2 6.0 ± 0.2
70 MIC-UNK-50cce87d-3 molecule Cc1cccc2c1c(cnc2)NC(=O)Cc3cccc(c3)Cl −8.24 ± 0.07 6.00 ± 0.05
71 ADA-UCB-6c2cb422-11 molecule COc1ccccc1CO[C@@H](c2cccc(c2)Cl)C(=O)Nc3cc(=O)[nH]c4c3cccc4 −8.2 ± 0.2 6.0 ± 0.2
72 JOH-UNI-3fc3434e-7 molecule CN(c1cncc2c1cccc2)C(=O)C(CC#N)c3cccc(c3)Cl −8.2 ± 0.2 6.0 ± 0.2
73 PET-UNK-6c2be958-1 molecule c1ccc2c(c1)cncc2N(C(=O)Cc3cccc(c3)Cl)C(=O)CCl −8.2 ± 0.2 6.0 ± 0.1
74 MAK-UNK-c749d764-22 molecule CC(CNCC1CCCO1)C(c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −8.2 ± 0.2 5.9 ± 0.1
75 PET-UNK-e274cad4-1 molecule Cn1c2c(cncc2NC(=O)Cc3cccc(c3)Cl)cn1 −8.2 ± 0.1 5.95 ± 0.09
76 PET-UNK-1320d94d-22 molecule CN(C)C(=O)[C@H]1CC[C@H](O1)C(=O)N(C)[C@@H](c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −8.1 ± 0.2 5.9 ± 0.1
77 JOH-UNI-a38a7bdd-1 molecule c1ccc2c(c1)cncc2N(C(=O)Cc3cccc(c3)Cl)C(=O)C(F)(F)F −8.1 ± 0.2 5.9 ± 0.1
78 MAT-POS-f7918075-7 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncc3c2CC(=O)N3 −8.1 ± 0.1 5.9 ± 0.1
79 EDJ-MED-00c1612e-1 molecule COc1ccc2cncc(c2c1)NC(=O)Cc3cccc(c3)Cl −8.12 ± 0.08 5.91 ± 0.05
80 MAK-UNK-ffc90da7-4 molecule CC(CNCC1CCCO1)C(c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −8.1 ± 0.2 5.9 ± 0.1
81 PET-UNK-ac320b15-6 molecule c1ccc2c(c1)cncc2NC(=O)[C@H](c3cccc(c3)Cl)NC(=O)[C@H]4CC[C@@H](O4)C(=O)N5CCCC5 −8.1 ± 0.3 5.9 ± 0.2
82 MAT-POS-29385cc1-4 molecule Cc1cc(cc2c1c(cnc2)NC(=O)Cc3cccc(c3)Cl)F −8.10 ± 0.10 5.90 ± 0.07
83 PET-UNK-8df914d1-1 molecule COc1ccc2cncc(c2c1)NC(=O)Cc3cccc(c3)Cl −8.1 ± 0.1 5.87 ± 0.09
84 MAK-UNK-c749d764-6 molecule CC(CNCCCO)C(c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3 −8.0 ± 0.2 5.9 ± 0.2
85 PET-UNK-12d8d43f-1 molecule c1ccc2c(c1)cncc2N(C=O)C(=O)Cc3cccc(c3)Cl −8.0 ± 0.1 5.85 ± 0.10
86 MAK-UNK-ffc90da7-1 molecule CC(CNCCCO)C(c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3 −8.0 ± 0.2 5.8 ± 0.2
87 JIN-POS-6dc588a4-11 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncc3c2ccc(c3)F −7.99 ± 0.07 5.82 ± 0.05
88 PET-UNK-1320d94d-27 molecule CN([C@H](c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3)C(=O)[C@@H]4C[C@@H](O4)C(=O)N5CCCC5 −8.0 ± 0.2 5.8 ± 0.2
89 PET-UNK-1320d94d-2 molecule CN(C)C(=O)[C@H]1CC[C@H](O1)C(=O)N[C@@H](c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4 −8.0 ± 0.2 5.8 ± 0.1
90 VLA-UCB-05e51b3f-15 molecule c1ccc2c(c1)cncc2N(C(=O)Cc3cccc(c3)Cl)C(=O)CCl −7.9 ± 0.2 5.8 ± 0.1
91 MIC-UNK-50cce87d-2 molecule c1cc(cc(c1)Cl)CC(=O)Nc2cncc3c2c(ccc3)Cl −7.9 ± 0.1 5.76 ± 0.08
92 RUB-POS-1325a9ea-4 molecule Cc1ccc2cncc(c2c1)NC(=O)Cc3cccc(c3)Cl −7.91 ± 0.07 5.76 ± 0.05
93 PET-UNK-1320d94d-26 molecule CN([C@@H](c1cccc(c1)Cl)C(=O)Nc2cncc3c2cccc3)C(=O)[C@@H]4CC[C@@H](O4)C(=O)N5CCC5 −7.9 ± 0.2 5.8 ± 0.1
94 EDJ-MED-ee07cf00-7 molecule Cc1c(c(=O)ccn1CC(=O)NC(c2cccc(c2)Cl)C(=O)Nc3cncc4c3cccc4)O −7.9 ± 0.3 5.7 ± 0.2
95 PET-UNK-a692de38-1 molecule c1ccc2c(c1)cncc2N(C(=O)Cc3cccc(c3)Cl)NC#N −7.9 ± 0.2 5.7 ± 0.2
96 MIC-UNK-5a93dd5f-1 molecule c1ccc2c(c1)cncc2NC(=O)C(c3cccc(c3)Cl)N4CC5CCCC5C4 −7.9 ± 0.1 5.7 ± 0.1
97 EDJ-MED-cf4b0d25-3 molecule c1ccc2c(c1)cncc2NC(=O)C(c3cccc(c3)Cl)NC(=O)[C@@H]4CCCO4 −7.84 ± 0.06 5.71 ± 0.05
98 RUB-POS-1325a9ea-15 molecule Cn1c2cncc(c2cn1)NC(=O)Cc3cccc(c3)Cl −7.8 ± 0.1 5.71 ± 0.10
99 EDG-MED-0da5ad92-18 molecule Cc1ccnc(c1NC(=O)Cc2cccc(c2)Cl)N −7.81 ± 0.08 5.69 ± 0.06
100 MAT-POS-29385cc1-2 molecule COc1cc2cncc(c2cc1F)NC(=O)Cc3cccc(c3)Cl −7.8 ± 0.1 5.69 ± 0.09

Raw data

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Structures

Last updated 2021-08-24T20:34:29.621440+00:00
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