Submission Details
Molecule(s):
Cc1cc(C(=O)CSc2ncc(C#N)c(N)n2)c(C)n1C
CCc1nc(SCC(=O)NCc2ccco2)[nH]c(=O)c1C#N
CCc1nc(SCC(=O)NCCOC)[nH]c(=O)c1C#N
CCc1nc(SCC(=O)NCC(C)C)[nH]c(=O)c1C#N
COCc1cc(C)nc(SCC(=O)OC(C)C)c1C#N
N#CCCn1c(=O)n(CCC#N)c(=O)n(CCC#N)c1=O
CSc1nc(N)nc(SCC(=O)C(C)(C)C)c1C#N
N#Cc1cnc(SCC(=O)N2CCCC2)nc1N
COCc1cc(C)nc(SCC(=O)NC(C)(C)C)c1C#N
CCOC(=O)CSc1nc(CC)c(C#N)c(=O)[nH]1
CCC(=O)Nc1nnc(SCC#N)s1
CCOc1ccc(NC(=O)CSc2nc(CC)c(C#N)c(=O)[nH]2)cc1
N#CCCCOc1ccc2c(c1)OCO2
Cc1csc(NC(=O)CSc2ncccc2C#N)n1
CCc1nc(SCC(=O)OC(C)C)[nH]c(=O)c1C#N
CCc1nc(SCC(=O)Nc2ccc(OC)cc2)[nH]c(=O)c1C#N
COCc1cc(C)nc(SCC(=O)Nc2cccc(F)c2)c1C#N
COCc1cc(C)nc(SCC(=O)O)c1C#N
CCc1nnc(NC(=O)CN(C)CCC#N)s1
Cc1cnc(NC(=O)CSc2ncccc2C#N)s1
CC(C)(C#CCN1CCOCC1)OCCC#N
N#Cc1cnc(SCC(=O)Nc2nccs2)nc1N
CCc1nc(SCC(=O)OC)[nH]c(=O)c1C#N
CCc1nc(SCC(=O)Nc2ccc(F)c(Cl)c2)[nH]c(=O)c1C#N
COc1ccc(NC(=O)NC(C)(C)C#N)cc1
Cc1nnc(NC(=O)CSc2ncccc2C#N)s1
CN1CCc2nc(SCC(=O)NC(C)(C)C)c(C#N)cc2C1
COCc1cc(C)nc(SCC(=O)Nc2nc(C)cs2)c1C#N
COCc1cc(C)nc(SCC(=O)Nc2ncc(C)s2)c1C#N
Cn1c(=O)c2c(nc(SCC#N)n2C)n(C)c1=O
CC(=O)c1cc(C#N)c(SCC(N)=O)nc1C
COCc1cc(C)nc(SCC(=O)Nc2ccc(F)cc2)c1C#N
CCc1nnc(NC(=O)CSc2ncccc2C#N)s1
CC(=O)N1CCC(C(=O)NCC#N)CC1
CCCOc1ccc(NC(=O)CSc2ncc(C#N)c(N)n2)cc1
COCCNc1oc(COc2ccc(F)cc2)nc1C#N
CCOC(=O)CC(=O)CSc1nccc(N(C)C)c1C#N
N#CCSc1nc(N2CCOCC2)nc(N2CCOCC2)n1
N#CCSc1nc2ccc(N)cc2s1
CC(Sc1ncccc1C#N)C(=O)Nc1nccs1
Cn1c(=O)c2c(ncn2CCCC#N)n(C)c1=O
CCCN1CC(C(=O)NCC#N)CC1=O
N#Cc1ccsc1NC(=O)CCCOc1ccc(Cl)cc1Cl
N#CCCS(=O)(=O)c1cc(Cl)ccc1Cl
N#Cc1cnc(SCC(=O)Nc2ccc(Cl)c(Br)c2)nc1N
N#Cc1cccnc1SCC(=O)Nc1ccc(Cl)c(Cl)c1
MAR-TRE-6c5ef77a-47
Duplicate of:
MAR-TRE-f5c2d31c-6
CSc1nc(N)nc(SCC(=O)Nc2cccc(F)c2)c1C#N
CC(=O)c1cc(C#N)c(SCC(=O)O)nc1C
CC(=O)c1cnc2nc(SCC#N)nn2c1C
N#CCCCn1c(=O)oc2ccc(Cl)cc21
N#Cc1cccnc1SCC(=O)Nc1ccc(F)c(Cl)c1
CC(C)c1nc(CC#N)n[nH]1
Cc1nc(C#N)c(NCc2ccco2)o1
N#CCSc1nc2cc(Cl)ccc2[nH]1
Cc1nc2ccc(NC(=O)CSc3ncccc3C#N)cc2[nH]1
Cc1ccc(-c2nn(CCC#N)cc2/C=N/O)o1
N#CCNC(=O)COc1ccc(Cl)cc1
CCCOc1ccc(NC(=O)CSc2ncccc2C#N)cc1
CN(C)c1nc(NC(C)(C)C)nc(SCC#N)n1
COCc1cc(C)nc(SC)c1C#N
CN(CCC#N)CC(=O)Nc1nccs1
CC(=O)Nc1ccc(NCCC#N)cc1
N#CCCNCCN1CCCC1=O
CCOc1ccc(NC(=O)CSc2ncccc2C#N)cc1
COc1ccc(OCCC#N)cc1
N#Cc1cccnc1SCC(=O)Nc1ccc(F)cc1
COc1ccc(NC(=O)CSc2ncccc2C#N)cc1
CC(=O)c1cc(C#N)c(SCC(=O)Nc2nccs2)nc1C
CCOC(=O)c1c(C)oc(N)c1C#N
CNc1oc(COc2ccc(Cl)cc2)nc1C#N
CC(=O)c1cc(C#N)c(SCC(=O)OC(C)(C)C)nc1C
Cn1c(=O)c2cc(C#N)c(N)nc2n(C)c1=O
COC(=O)c1c(N)c(C#N)cn1C
CSc1nc(N)nc(SCC(=O)Nc2ccc(Cl)cc2)c1C#N
CCOCCCNc1oc(COc2ccc(F)cc2)nc1C#N
CCOC(=O)c1c(N)c(C#N)cn1C
N#Cc1cc(Cl)ccc1OCC(=O)O
Cc1nnc(SCC#N)s1
CCNc1sc(C(C)=O)c(N)c1C#N
C=CCNc1oc(COc2cccc(Cl)c2)nc1C#N
Cc1nc2ncc(C#N)c(N)n2n1
CCc1nc(SC(C)C(=O)Nc2cccc(Cl)c2C)[nH]c(=O)c1C#N
CN(C)c1nc(SCC#N)nc(N2CCOCC2)n1
CC1(C)Cc2nc(NCCO)c(C#N)cc2CO1
CCc1nc(SC(C)C(=O)Nc2ccc(Cl)cc2)[nH]c(=O)c1C#N
CCc1nc(SC(C)C(=O)Nc2ccc(F)cc2)[nH]c(=O)c1C#N
CCOC(=O)c1csc(CC#N)n1
CC(C)(C#CCN1CCCC1)OCCC#N
CSc1nc(C)c(C(C)=O)cc1C#N
Cn1nnnc1SCC#N
CN(C)c1nc(SCC#N)nc(N(C)C)n1
CCc1nc(SCC(=O)Nc2ccc(F)cc2)[nH]c(=O)c1C#N
Cc1cc(C(=O)CSc2ncccc2C#N)c(C)n1C
COCc1c(Br)c(C)nc(OCC(=O)O)c1C#N
N#Cc1cnc2ncnn2c1N
Cc1cc(Cl)ccc1NC(=O)CSc1ncccc1C#N
Cc1nc(C)c(CC#N)s1
COc1nc(C#N)c(N(C)C)o1
CCOC(=O)COc1nc(C)c(Br)c(COC)c1C#N
CCOC(=O)/C(C#N)=C1\C=CN(C)C(C)=N1
Design Rationale:
A nitrile group is an attractive covalent bonding warhead for cysteine proteases because the proximity of the HIS(41) residue facilitating the formation of the SG-C(=N-H)R binding complex. Selectivity is then possible by non-covalent interactions elsewhere in the binding site. This selection of 500 molecules from nearly 8,000 commercially available nitriles in the ChemBridge Express Pick collection are predicted to bind using the THINK software (https://treweren.com) into the 6WNP crystal structure (which has a slightly more favourable geometry than 5RF7). These hits were partitioned by lipophilicity (as calculated by the software) in to 5 sets. This is set 1 of 5.
Other Notes:
A SD file of the 3D binding coordinates is available.