Submission Details
Molecule(s):
Cc1ccc(S(=O)(=O)Nc2c(-c3cccnc3)nc3ccccn23)c(C)c1
CCN1CCN(Cc2ccccc2CNC2=NC[C@@H](C3CCCC3)N2)CC1
CCN1CCN(Cc2ccccc2CNC(=O)[C@@]2(C)CCN2C(=O)OC(C)(C)C)CC1
CCOC(=O)[C@@H](CCc1ccccc1)N[C@H](C)C(=O)Nc1cccc(CN2CCCC2)c1
O=C(O)[C@@H](Cc1nc(=O)cc[nH]1)NCc1ccc(Cl)s1
Cc1ccc(NCc2cc(NC(=O)OC(C)(C)C)ccc2Br)cn1
Cc1cc(C(C)(C)C)ccc1OC[C@H](O)Cn1cnccc1=O
C[C@H]1CN(Cc2ccccc2)CC[C@@H]1NC(=O)C(=O)NCc1ccccc1CN1CCCC[C@@H]1C
O=C(O)[C@@H](Cc1nc(=O)cc[nH]1)NC[C@@H]1C[C@@H]2C=C[C@H]1C2
O=C(NCc1ccccc1OCCO)C(=O)N[C@H]1C[C@H]1C1CCOCC1
CC[C@@H]1CN=C(NCc2ccccc2CN2CCN(CC)CC2)N1
O=S(=O)(Cc1nc(-c2ccncc2)no1)Nc1ccc(N2CCCCC2)cc1
O=C(c1ccccc1)N1C[C@@H](CNCc2c[nH]cn2)N2CC[C@H]1C2
Design Rationale:
We applied a new approach named "Chemical Space Docking" to mine Enamine's REAL Space for compounds with a high potential to be good binders. REAL Space is based on reliable reactions and off-the-shelf building blocks from Enamine. It contains billions of molecules, which prohibits brute-force docking. Our new method exploits an anchor-and-grow strategy that circumvents the problem of the combinatorial explosion. Our Chemical Space Docking was performed using 4 non-covalent fragment binders as starting-points. This led to almost 2 mio molecules and a total of 8 million docking poses. These were scored and filtered followed by visual selection of 13 molecules from the top of the list.
Other Notes:
An SD file with the 3D poses of the molecules is deposited here: https://www.biosolveit.de/transfer/d/665ce8c70e728a74b114f819b2429900061d9d92/selected.sdf Correlation between smiles and Enamine order number: S(=O)(=O)(NC=1N2C(=NC1c3cnccc3)C=CC=C2)c4c(cc(cc4)C)C --> s232682__6950814__3005078; [NH+]1=C(N[C@H](C2CCCC2)C1)NCc3c(cccc3)C[NH+]4CC[NH+](CC4)CC --> s276492__14269936__14695664; O=C(OC(C)(C)C)N1[C@@](C(=O)NCc2c(cccc2)C[NH+]3CC[NH+](CC3)CC)(CC1)C --> s22__677414__15065722; O=C(OCC)[C@H]([NH2+][C@@H](C(=O)Nc1cc(ccc1)C[NH+]2CCCC2)C)CCc3ccccc3 --> s22__625048__12423058; ClC=1SC(=CC1)C[NH2+][C@@H](C([O-])=O)CC2=NC(=O)C=CN2 --> s271304__15071844__9305138; Brc1c(cc(NC(=O)OC(C)(C)C)cc1)CNc2cnc(cc2)C --> s270004__8298878__14783060; O=C1N(C=NC=C1)C[C@@H](O)COc2c(cc(cc2)C(C)(C)C)C --> s63__6670848__64507; O=C(N[C@@H]1[C@H](C[N@H+](Cc2ccccc2)CC1)C)C(=O)NCc3c(cccc3)C[N@@H+]4[C@H](CCCC4)C --> s271948__9939400__9926964; [O-]C(=O)[C@H]([NH2+]C[C@H]1[C@H]2C=C[C@@H](C1)C2)CC3=NC(=O)C=CN3 --> s271304__15071844__9304654; O=C(N[C@@H]1[C@H](C2CCOCC2)C1)C(=O)NCc3c(OCCO)cccc3 --> s271948__12640900__15268182; [NH+]1=C(N[C@@H](C1)CC)NCc2c(cccc2)C[NH+]3CC[NH+](CC3)CC --> s276492__14269838__14695664; S(=O)(=O)(Nc1ccc(N2CCCCC2)cc1)CC=3ON=C(N3)c4ccncc4 --> s265764__4837050__4564564; O=C(N1[C@@H]2C[N@H+]([C@H](C[NH2+]CC=3N=CNC3)C1)CC2)c4ccccc4 --> s207__7974616__11756618;