Submission Details
Molecule(s):
O=C(Cc1ccccc1O)N1CCOC2(CCN(Cc3cncnc3)CC2)C1
O=C(CCc1cn[nH]c1)N1CCOC2(CCN(Cc3cncnc3)CC2)C1
Cc1nc(N)nc(C)c1CC(=O)N1CCOCC1CC(=O)Nc1ccccc1
Nc1ccnc(N2CCC3(CC2)CN(C(=O)Cc2cccs2)CCO3)n1
O=C(CN1CCCC2(CCc3cnc(-c4ccccc4)nc32)C1)N1CCOCC1
CCc1nccc(CN2CCC3(CC2)CN(C(=O)NC(C)(C)C)CCO3)n1
O=C(NCc1cn2cccnc2n1)C1CNCC(C(=O)N2CCOCC2)C1
CCCCSc1nc(N)cc(N2CCCC(C(=O)N3CCOCC3)C2)n1
COc1cccc(CC2CN(C(=O)Cc3c(C)nc(N)nc3C)CCO2)c1
Cc1nc(CC(=O)N2CCOC3(CCN(c4ncccn4)CC3)C2)cs1
CNc1nc(C)cc(N2CCC(N3CCCC(C(=O)N4CCOCC4)C3)CC2)n1
CNc1ccnc(N2CCC(N3CCCC(C(=O)N4CCOCC4)C3)CC2)n1
Cc1nc2c(N3CCC(C(=O)N4CCOCC4)CC3)ncnc2o1
O=C(C1CNCC(C(=O)N2CCC(c3ccncn3)CC2)C1)N1CCOCC1
O=C(CN1CCN(c2ncccn2)CC1)N1CCOC(c2ccccc2)C1
CN(C)c1ncc2c(n1)C1(CCCN(CC(=O)N3CCOCC3)C1)CC2
CC1CN(C(=O)CN2CCC(Nc3ncccn3)C(O)C2)CC(C)O1
Nc1ncc2c(n1)C1(CCCN(CC(=O)N3CCOCC3)C1)CC2
Nc1cc(N2CCC(N3CCCC(C(=O)N4CCOCC4)C3)CC2)ncn1
Cc1ncc2c(n1)C1(CCCN(CC(=O)N3CCOCC3)C1)CC2
CC(=O)N1CCOC(CNc2nc(C)nc(O)c2Cl)C1
O=C(CCc1ccc2c(c1)OCO2)N1CCOC2(CCN(c3ncccn3)C2)C1
COc1cc(C(=O)NCC2CN(C(C)=O)CCO2)nc(OC)n1
O=C(O)CC1COCCN1C(=O)c1ccc(CSc2ncccn2)o1
O=C(C1CCCN(c2nccc(-c3cccnc3)n2)C1)N1CCOCC1
CSc1ncc(CN2CCCC(CCC(=O)N3CCOCC3)C2)cn1
CCCCSc1nc(N)cc(N2CCC(C(=O)N3CCOCC3)CC2)n1
Cc1nc(O)nc(C)c1CCC(=O)N1CCOC(c2cccnc2)C1
O=C(c1ccc(-c2cncnc2)o1)N1CCOCC1
O=C(C1CNCC(C(=O)N2CCN(c3ncccn3)CC2)C1)N1CCOCC1
O=C(C1CCCN1Cc1cnc(C2CCCCC2)nc1)N1CCOCC1
CC(=O)N1CCOC(CNc2cc(-c3ccccc3)nc3ccnn23)C1
Cc1nc(C2CCCN(CC(=O)N3CCOCC3)C2)cc(N2CCCC2)n1
CC(=O)N1CCOC(CNc2ncc(C#N)c(N)n2)C1
Cc1nccc(N2CCC3(CC2)CN(C(=O)C(C)N2CCCC2=O)CCO3)n1
CCC1COCCN1C(=O)c1coc(CN2CCN(c3ncccn3)CC2)n1
CN(C)c1ncc(CN2CCC(CCC(=O)N3CCOCC3)CC2)cn1
CCC1COCCN1C(=O)CCc1c(C)nc(O)nc1C
O=C(C1CCN(c2cc(C3CCOC3)ncn2)CC1)N1CCOCC1
CC(=O)c1cnc(N2CCC(C(=O)N3CCOCC3)CC2)nc1C
CSc1ncc(CN2CCC(CCC(=O)N3CCOCC3)CC2)cn1
Cc1nccc(N2CCCn3nc(CCC(=O)N4CCOCC4)cc3C2)n1
CCc1cc(NCC2CN(C(C)=O)CCO2)nc(N2CCCCC2)n1
CCCC1COCCN1C(=O)CN1CCN(c2ncccn2)CC1
CCc1nccc(CN2CCC(C(=O)N3CCOCC3)CC2)n1
CC1CN(C(=O)CN2CCCC3(CCc4cnc(-c5ccccc5)nc43)C2)CC(C)O1
O=C(CSc1ncccn1)N1CCCC(C(=O)N2CCOCC2)C1
CC(=O)N1CCOC(CNc2cc(N3CCCCC3)ncn2)C1
O=C(CN1CCN(c2ncccn2)CC1)N1CCOC(c2ccc(F)cc2)C1
Design Rationale:
This batch is the top 49 hits selected from ChemBridge Core Library containing n1cnccc1 (an essential part of x0995) as well as O=CN2CCOCC2 ( an important part of x1249) which were docked using our THINK software (http://treweren.com) into 1093 (5RF3) using a 3 centre pharmacophore requiring interactions with residues observed to be strongly interacting with fragments in the non-covalent crystal structures: (41),(44),(140),(142),(143),(144),(163),(166),(189). They were scored using an enhanced ChemScore function which doesn't require explicit hydrogens or tautomers.
Other Notes:
These compounds are commercially available for HTS assays as solids for about $20 per sample (assuming a minimum purchase of around 100). As SD file of the docked conformations is available.