Submission Details
Molecule(s):
O=C(Cn1c(=O)n(Cc2ccccn2)c(=O)c2ncccc21)NCc1ccccc1
Cc1ccc(CNC(=O)Cn2c(=O)c3nnc(C)n3c3ncccc32)cc1C
CSc1ccc(CNC(=O)Cn2c(=O)c3nnc(C)n3c3ncccc32)cc1
CCc1ccc(CNC(=O)Cn2c(=O)c3nnc(C)n3c3ncccc32)cc1
O=C(Cn1c(=O)c2cc(C3CC3)nn2c2ncccc21)NCc1ccc(Cl)cc1
O=C(Cn1c(=O)n(Cc2cccs2)c(=O)c2ncccc21)NCc1ccc(F)cc1
O=C(Cn1c(=O)c2cc(C3CC3)nn2c2ncccc21)NCc1ccc(F)cc1
O=C(Cn1c(=O)c2cc(C3CC3)nn2c2ncccc21)NCc1cccc(Cl)c1
Nc1ccccc1CCC(=O)Nc1ccc(N2CCNC(=O)C2)nc1
COc1cccc(CNC(=O)Cn2c(=O)c3cc(C4CC4)nn3c3ncccc32)c1
Cc1cccc(CNC(=O)Cn2c(=O)c(=O)n(C)c3ncccc32)c1
O=c1c2ncccc2n(Cc2cccc(F)c2)c(=O)n1Cc1ccc2c(c1)OCO2
O=C(Cn1c(=O)n(Cc2cccnc2)c(=O)c2ncccc21)NC1CCCC1
O=c1c2ncccc2n(Cc2ccc(F)cc2)c(=O)n1Cc1ccc2c(c1)OCO2
COc1ccc(NC(=O)CCN2C(=O)c3ccccc3N3C(=O)c4ccccc4[C@@H]23)cn1
Cc1nnc2c(=O)n(CC(=O)NCC3CCCCC3)c3cccnc3n12
C[C@@H]1Sc2ccc(S(=O)(=O)CCC(=O)Nc3cccnc3)cc2NC1=O
COc1ccc(NC(=O)CCc2nc3sc4c(c3c(=O)[nH]2)CCCC4)cn1
COc1ccccc1CNC(=O)Cn1c(=O)c2cc(C3CC3)nn2c2ncccc21
Cc1ccc(-n2c(=O)n(CC(=O)NCc3ccc(F)cc3F)c3cccnc32)cc1
COc1ccc(CCn2c(=O)c3ncccc3n(Cc3cccc(F)c3)c2=O)cc1OC
CCc1nnc2c(=O)n(CC(=O)NCC3CCCCC3)c3cccnc3n12
Cc1ccc(C)c(CNC(=O)Cn2c(=O)c3nnc(C)n3c3ncccc32)c1
COc1ccc(CCn2c(=O)c3ncccc3n(Cc3cccc(Cl)c3)c2=O)cc1OC
O=C(Cn1c(=O)n(Cc2cccnc2)c(=O)c2ncccc21)NCCc1ccccc1
O=C(Cn1c(=O)c2cc(C3CC3)nn2c2ncccc21)NCc1cccs1
O=C(Cn1c(=O)n(-c2ccccc2)c2ncccc21)NCc1ccc(F)cc1F
O=C(Cn1c(=O)n(Cc2cccs2)c(=O)c2ncccc21)NCc1ccccc1Cl
Cc1ccccc1CNC(=O)Cn1c(=O)c2nncn2c2ncccc21
NC1(C(=O)Nc2ccc(N3CCNC(=O)C3)nc2)CCCCC1
COc1ccc(CCn2c(=O)c3ncccc3n(Cc3ccccc3Cl)c2=O)cc1OC
O=c1c2ncccc2n(Cc2ccccc2Cl)c(=O)n1Cc1cccnc1
O=c1c2ncccc2n(Cc2cccc(Cl)c2)c(=O)n1Cc1cccnc1
O=C(NCc1ccc([C@H](O)c2cccs2)s1)C(=O)Nc1cccnc1
CC(=O)Nc1ccc(-n2cnc(C(=O)NC3CCCCC3)c2)nc1
CCc1ccc(C(=O)Cn2c(=O)n(Cc3ccncc3)c(=O)c3ncccc32)cc1
O=c1c2ncccc2n(Cc2ccccc2F)c(=O)n1Cc1ccc2c(c1)OCO2
O=C(Cn1c(=O)n(Cc2ccc3c(c2)OCO3)c(=O)c2ncccc21)N1CCc2ccccc21
Cc1c(CC(=O)Nc2cccnc2)c(=O)oc2cc(O)c(Cl)cc12
C[C@H]1Cc2cc(S(=O)(=O)N(C)CC(=O)Nc3cccnc3)ccc2N1C(=O)C1CC1
O=c1c2ncccc2n(Cc2ccccc2F)c(=O)n1Cc1cccnc1
COc1ccc(Cn2c(=O)c3ncccc3n(CC(=O)Nc3ccccc3F)c2=O)cc1
O=C(Cn1c(=O)n(-c2ccccc2)c2ncccc21)NCc1ccc(F)cc1Cl
Cc1ccc(-c2ccccc2NC(=O)Cn2c(=O)n(Cc3cccs3)c3ncccc32)o1
Cc1ccc(CNC(=O)Cn2c(=O)n(Cc3cccnc3)c(=O)c3ncccc32)cc1
O=C(Cn1c(=O)n(Cc2cccnc2)c(=O)c2ncccc21)NCc1ccccc1
COc1cccc(CNC(=O)c2ccc(NC(=O)N3CCSc4ncccc43)cc2)c1
COc1ccc(CNC(=O)Cn2c(=O)n(-c3ccc(C)cc3)c3ncccc32)cc1OC
O=c1c2ncccc2n(Cc2ccc(F)cc2)c(=O)n1Cc1cccnc1
O=c1c2ncccc2n(Cc2cccc3ccccc23)c(=O)n1Cc1ccncc1
O=c1c2ncccc2n(Cc2cccc(F)c2)c(=O)n1Cc1ccccn1
CN1C(=O)N(CC(=O)Nc2cccnc2)C(=O)C12CCCCC2
O=C(C[C@@H]1NC(=O)N(C2CCCCC2)C1=O)Nc1cccnc1
CCc1ccc(CNC(=O)Cn2c(=O)c(=O)n(C)c3ncccc32)cc1
COc1ccc2cc(NC(=O)[C@@H](C)n3cnc4ccccc4c3=O)cnc2c1
O=C(Cn1c(=O)n(Cc2ccc3c(c2)OCO3)c(=O)c2ncccc21)c1ccccc1
COc1ccc(Cn2c(=O)c3ncccc3n(CC(=O)Nc3ccc(Br)cc3)c2=O)cc1
O=C(Cn1c(=O)n(Cc2ccccn2)c(=O)c2ncccc21)Nc1ccccc1
O=C(Cn1c(=O)n(-c2ccc(F)cc2)c2ncccc21)NCC1CCCCC1
COc1cccc(NC(=O)Cn2c(=O)n(Cc3ccccc3)c(=O)c3ncccc32)c1
Cc1nnc2c(=O)n(CC(=O)NCCC3=CCCCC3)c3cccnc3n12
O=c1c2ncccc2n(Cc2cccc(Cl)c2)c(=O)n1Cc1ccccn1
Nc1ccc(NC(=O)CN2C(=O)NC3(CCCCC3)C2=O)cn1
O=c1c2ncccc2n(Cc2ccccc2Cl)c(=O)n1Cc1ccc2c(c1)OCO2
COc1cccc(NC(=O)Cn2c(=O)n(CCc3ccccc3)c(=O)c3ncccc32)c1
C[C@H]1Cc2cc(S(=O)(=O)CCC(=O)Nc3cccnc3)ccc2N1C(=O)C1CC1
CC(C)n1ncc2cc(NC(=O)CCc3c[nH]c4ccccc34)cnc21
COc1ccc([C@@H](C)NC(=O)Cn2c(=O)n(-c3ccc(C)cc3)c3ncccc32)cc1OC
O=C(Cn1c(=O)c(=O)n(Cc2ccccc2)c2ncccc21)N1CCN(c2ccccc2)CC1
O=C(Nc1cccnc1)c1ccc2c(c1)C(=O)N(Cc1cccnc1)C2=O
N[C@H]1[C@H]2CC[C@@H](C2)[C@H]1C(=O)NCC(=O)Nc1cccnc1
COc1ccc([C@H]2[C@H](C(=O)Nc3ccc(N)nc3)CCC(=O)N2C)cc1
CN(C)c1cccc(C(=O)Nc2cccnc2SCCN2CCCCC2)c1
O=C(CCC1CCNCC1)NCC(=O)Nc1cccnc1
O=C(C[C@@H]1CSCCN1)Nc1ccc(NC(=O)C2CC2)nc1
O=c1c2ncccc2n(Cc2ccc(F)cc2)c(=O)n1Cc1ccccn1
C[C@@H](CC(=O)NCC(=O)Nc1cccnc1)[C@H]1CCCNC1
O=C(CCN1C(=O)/C(=C\c2cccs2)SC1=S)Nc1cccnc1
O=c1c2ncccc2n(Cc2cccc(Cl)c2)c(=O)n1Cc1ccc2c(c1)OCO2
N[C@@H]1CCC[C@@H]1CC(=O)NCCC(=O)Nc1cccnc1
O=C(CCNS(=O)(=O)c1ccc2c(c1)CCN2C(=O)C1CC1)Nc1cccnc1
COc1ccc(Cn2c(=O)c3ncccc3n(CC(=O)Nc3ccccc3)c2=O)cc1
C[C@H]1Cc2cc(S(=O)(=O)NCCC(=O)Nc3cccnc3)ccc2N1C(=O)C1CC1
O=C(Cn1c(=O)c2cc(C3CC3)nn2c2ncccc21)Nc1ccccc1F
COc1ccc(C2(C(=O)Nc3cccnc3)CCOCC2)cc1
O=c1c2ncccc2n(Cc2ccccc2F)c(=O)n1Cc1ccccn1
O=C1NC(=O)N(c2cccnc2)C(=O)/C1=C/c1cc(Br)cs1
O=C(NC[C@@H](O)c1csc2ccccc12)C(=O)Nc1cccnc1
COc1cccc(CNC(=O)CCC(=O)N2Cc3ccccc3Oc3ncccc32)c1
CCc1cccc(NC(=O)Cn2c(=O)c3cc(C)nn3c3ncccc32)c1
O=C(CN1C(=O)NC2(CCCC2)C1=O)Nc1cccnc1
CC(=O)Nc1ccc(-n2cnc(C(=O)NCCC3=CCCCC3)c2)nc1
Cc1nnc2c(=O)n(CC(=O)NC3CCCCC3)c3cccnc3n12
C[C@@H](c1ccccc1)n1c(=O)n(Cc2ccc3c(c2)OCO3)c(=O)c2ncccc21
CC(=O)Nc1ccc(-n2cnc(C(=O)NC3CCC(C)CC3)c2)nc1
N[C@@H]1CCC[C@@H]1CC(=O)N1CC(=O)Nc2cnccc21
N[C@H]1CCC[C@H](C(=O)NCC(=O)Nc2cccnc2)C1
COc1ccc([C@@H](C)NC(=O)Cn2c(=O)n(-c3ccccc3)c3ncccc32)cc1
Cc1cccc(CNC(=O)C[C@H]2Sc3ncccc3N(C)C2=O)c1
C[C@@H](NC(=O)Cn1c(=O)n(-c2ccccc2)c2ncccc21)c1ccccn1
Design Rationale:
The Akos screening library is vast and includes a large number of molecules containing the 3-amino-pyridine substructure found in fragment x0678. We docked these molecules with 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. We selected the best 1,000 hits and partitioned them by lipophilicity (as calculated by the software) in to 10 sets. This is set 8 of 10.
Other Notes:
SD files of the docked molecules are available.