Submission Details
Molecule(s):
Cc1nnc2c(=O)n(CC(=O)NCc3ccc(C(C)C)cc3)c3cccnc3n12
O=C(Cn1c(=O)n(Cc2ccccc2)c(=O)c2ncccc21)NCc1ccc(F)cc1
Cc1ccc(CNC(=O)Cn2c(=O)n(Cc3ccccn3)c(=O)c3ncccc32)cc1
CC(C)c1ccc(CNC(=O)Cn2c(=O)c3nncn3c3ncccc32)cc1
O=C(CCN1C(=O)c2ccccc2N2C(=O)c3ccccc3[C@@H]12)Nc1cccnc1
O=C(Cn1c(=O)c2cc(C3CC3)nn2c2ncccc21)NCc1ccccc1
CC[C@@H]1Sc2ccc(S(=O)(=O)CCC(=O)Nc3cccnc3)cc2NC1=O
O=C(Cn1c(=O)n(Cc2cccnc2)c(=O)c2ncccc21)NC1CCCCC1
O=C(Cn1c(=O)n(C2CCCCC2)c2ncccc21)NCc1ccc(F)cc1F
O=C(Cn1c(=O)n(Cc2ccccn2)c(=O)c2ncccc21)NC1CCCCC1
COc1ccc([C@@H](C)NC(=O)Cn2c(=O)n(C3CCCCC3)c3ncccc32)cc1
COc1ccccc1CNC(=O)Cn1c(=O)c(=O)n(Cc2ccc(C)cc2)c2ncccc21
O=C1c2ccc(Br)cc2C(=O)N1c1cccnc1
N#Cc1cccc(C(=O)NCCn2c(=O)n(Cc3ccccc3)c3cccnc32)c1
COc1ccc(CCn2c(=O)c3ncccc3n(Cc3cccc(C)c3)c2=O)cc1OC
O=C(Cn1c(=O)c2cc(C3CC3)nn2c2ncccc21)N1CCc2ccccc21
O=C(Nc1cccnc1)[C@@H]1CCCN(S(=O)(=O)c2ccc(Cl)cc2)C1
COc1ccc(CCn2c(=O)c3ncccc3n(Cc3ccccc3C)c2=O)cc1OC
N[C@H](CC(=O)Nc1ccc(NC(=O)C2CC2)nc1)c1ccccc1
COc1cccc(CNC(=O)Cn2c(=O)n(C3CCCCC3)c3ncccc32)c1
O=C(Cn1c(=O)n(-c2ccccc2)c2ncccc21)NCc1ccc(Cl)cc1
CCc1ccccc1NC(=O)Cn1c(=O)n(Cc2ccccn2)c(=O)c2ncccc21
O=C(Cn1c(=O)n(Cc2cccs2)c(=O)c2ncccc21)NCc1ccccc1
Cc1ccc(C)c(NC(=O)Cn2c(=O)n(Cc3ccccn3)c(=O)c3ncccc32)c1
COc1ccccc1CNC(=O)Cn1c(=O)n(C2CCCCC2)c2ncccc21
Cc1ccccc1Cn1c(=O)n(Cc2cccnc2)c(=O)c2ncccc21
O=C(Cn1c(=O)c2cc(C3CC3)nn2c2ncccc21)NCCc1ccccc1
O=C(Cn1c(=O)n(Cc2ccc3c(c2)OCO3)c(=O)c2ncccc21)N1CCCc2ccccc21
O=C(Cn1c(=O)n(Cc2cccs2)c(=O)c2ncccc21)c1ccc(F)cc1
CC(=O)c1ccc(NC(=O)Cn2c(=O)n(Cc3ccccc3)c(=O)c3ncccc32)cc1
O=C(CCCSc1ccc(NC(=O)C2CC2)nn1)Nc1cccnc1
O=C(CCC(=O)N1Cc2ccccc2Oc2ncccc21)NCCc1ccc(Cl)cc1
COc1cccc(CNC(=O)Cn2c(=O)n(-c3ccc(C)cc3)c3ncccc32)c1
NC(=O)c1cccc(Cc2ccc(NC(=O)CN3CCCCC3)cn2)c1
O=C(Nc1cccnc1)[C@@H]1CCCN(S(=O)(=O)c2ccc(F)cc2)C1
O=C(Cn1c(=O)n(C2CCCC2)c2ncccc21)NCc1ccc(Cl)cc1
Cc1cccc(Cn2c(=O)n(Cc3ccc4c(c3)OCO4)c(=O)c3ncccc32)c1
Nc1ccc(NC(=O)CCS(=O)(=O)c2ccc3c(c2)CCC3)cn1
COc1ccc(NC(=O)c2cn(-c3ccccc3OC)c(=O)c3ccccc23)cn1
C[C@H]1CCC[C@H](C(=O)Nc2cnn(CC(=O)Nc3cccnc3)c2)C1
Cc1c(CC(=O)Nc2cccnc2)c(=O)oc2cc(O)ccc12
CCc1cccc(NC(=O)Cn2c(=O)n(Cc3ccccn3)c(=O)c3ncccc32)c1
Cc1cccc(NC(=O)Cn2c(=O)n(Cc3ccccn3)c(=O)c3ncccc32)c1
CCC1CCC2(CC1)NC(=O)N(CC(=O)Nc1ccc(N)nc1)C2=O
O=C(Cn1c(=O)n(-c2ccccc2)c2ncccc21)NCc1ccccc1F
O=C(Nc1cccnc1)[C@@H]1CCCN(S(=O)(=O)c2ccccc2)C1
O=C(C[C@H]1CCOc2ccccc21)N1CCSc2ncccc21
O=C(Nc1ccc(NC(=O)[C@H]2CCCNC2)cn1)C1CC1
O=C(Nc1cccnc1)[C@@H]1CCCN(S(=O)(=O)c2cccs2)C1
O=c1c2ncccc2n(Cc2ccccc2)c(=O)n1Cc1cccnc1
Cc1ccc2[nH]cc(CCC(=O)NCC(=O)Nc3cccnc3)c2c1
O=C(Cn1c(=O)n(-c2ccccc2)c2ncccc21)NCc1ccc(F)cc1
O=C(CCC1CCNCC1)Nc1ccc(C(=O)Nc2cccnc2)c(Cl)c1
N#Cc1cccc(C(=O)NCCn2c(=O)n(Cc3ccc(F)cc3)c3cccnc32)c1
O=C(Cn1c(=O)c(=O)n(Cc2ccccc2)c2ncccc21)NCCc1ccccc1Cl
COc1ccc(CNC(=O)Cn2c(=O)n(C3CCCC3)c3ncccc32)cc1
COc1ccc([C@@H](C)NC(=O)Cn2c(=O)n(-c3ccc(C)cc3)c3ncccc32)cc1
COc1cccc(CNC(=O)Cn2c(=O)n(-c3ccccc3)c3ncccc32)c1
Cc1ccc(C(=O)Cn2c(=O)n(Cc3cccnc3)c(=O)c3ncccc32)c(C)c1
O=C(Cn1c(=O)n(-c2ccccc2)c2ncccc21)NCc1cccc(F)c1
O=c1c2ncccc2n(Cc2ccccc2)c(=O)n1Cc1ccc2c(c1)OCO2
C[C@H]1CCCC[C@]12NC(=O)N(CC(=O)Nc1ccc(N)nc1)C2=O
O=C(Cn1c(=O)n(C2CCCC2)c2ncccc21)NCc1ccc(F)cc1
Cc1c(CCC(=O)Nc2cccnc2)c(=O)oc2c(C)c(O)ccc12
O=C(Nc1cccnc1)c1ccc(CNS(=O)(=O)c2cccc(Cl)c2)cc1
Cc1ccc(CNC(=O)Cn2c(=O)n(Cc3cccs3)c(=O)c3ncccc32)cc1
COc1ccc(Cn2c(=O)c3ncccc3n(CC(=O)Nc3ccc(C)cc3)c2=O)cc1
O=C(CCN1C(=O)c2ccccc2C1=O)Nc1cccnc1NC1CCCC1
O=C(Cn1c(=O)n(-c2ccccc2)c2ncccc21)NCc1ccccc1Cl
COc1ccccc1CNC(=O)Cn1c(=O)n(-c2ccc(C)cc2)c2ncccc21
O=C(CSCc1nc(O)c2ccccc2n1)Nc1cccnc1
O=C(Cn1c(=O)n(C2CCCC2)c2ncccc21)NCc1cccc(F)c1
Cc1ccc(Cn2c(=O)c(=O)n(CC(=O)NCc3ccc(F)cc3)c3cccnc32)cc1
Cc1ccc(Cn2c(=O)c(=O)n(CC(=O)NCc3ccccc3F)c3cccnc32)cc1
COc1cc(CCC(=O)N2CCN(Cc3ccc(C)cc3)c3ncccc32)cc(OC)c1OC
C[C@@H](O)c1ccc(C2(CNC(=O)C(=O)Nc3cccnc3)CCCC2)s1
Cn1c(=O)c(=O)n(CC(=O)N[C@H]2CCCc3ccccc32)c2cccnc21
Nc1ccc(NC(=O)C2(c3cccc(Cl)c3)CCOCC2)cn1
CNc1ccc(NC(=O)[C@@H]2CCCO[C@@H]2c2ccccc2)cn1
Cc1ccc(-n2c(=O)n(CC(=O)NCc3cccnc3)c3cccnc32)cc1
NCC1(CC(=O)NCC(=O)Nc2cccnc2)CCCCC1
COCc1nc2c(NC(=O)C3CCCCC3)cccn2n1
O=c1c(NCCc2cccnc2)nc2ccncc2n1Cc1ccccc1
O=C(CNCC1CC1)Nc1ccc(NC(=O)C2CC2)nc1
O=C(Nc1ccc(NC(=O)[C@@H]2CCCCN2)cn1)C1CC1
O=C(Nc1cccnc1)C1(n2cnnn2)CCCCC1
Cc1[nH]c2ccccc2c1[C@H]1c2ccccc2C(=O)N1CCC(=O)Nc1cccnc1
O=C(Cc1ccccc1Cl)NCCn1c(=O)n(Cc2ccc(F)cc2)c2cccnc21
C[C@H]1CCCCN1CCNC(=O)Cn1c(=O)n(C2CCCCC2)c2ncccc21
CCC[C@@H](N)C(=O)NCc1ccc(C(=O)Nc2cccnc2)cc1
Cc1ccc2ncc(NC(=O)NCC#N)c(O)c2c1
O=C(Cn1c(=O)n(Cc2ccccc2)c(=O)c2ncccc21)NCc1ccccc1Cl
O=C(CCCc1nnc2ccccn12)Nc1cccnc1
COc1ncc(NC(=O)[C@@H]2C[C@H]3CCCC[C@H]3N2)cc1C(N)=O
O=C(CNC(=O)[C@@H]1C[C@H]2CCCC[C@H]2N1)Nc1cccnc1
Cc1cc2c(=O)[nH]c(CSCC(=O)Nc3cccnc3)nc2s1
O=C(CCS(=O)(=O)Cc1ccccc1)Nc1cccnc1
Cc1ccccc1Cn1c(=O)n(Cc2ccc3c(c2)OCO3)c(=O)c2ncccc21
Cc1ccc(NC(=O)Cn2c(=O)n(Cc3ccccn3)c(=O)c3ncccc32)c(C)c1
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 9 of 10
Other Notes:
SD files of the docked molecules are available.