Submission Details
Molecule(s):
N#Cc1cnc(SCC(=O)NCCc2ccccc2)nc1N
CCc1nc(SCC(=O)NC2CCCCC2)[nH]c(=O)c1C#N
N#CCNC(=O)Cn1c(=O)[nH]c2ccccc2c1=O
N#Cc1cnc(SCC(=O)N2CCc3cc(Br)ccc32)nc1N
N#Cc1cnc(SCC(=O)N2CCc3ccccc32)nc1N
CCOC(=O)CSc1ncc2c(c1C#N)CCC2
N#CCSc1ncnc2c1oc1ccccc12
COCc1cc(C)nc(SCC(=O)N2CC(C)CC(C)C2)c1C#N
N#Cc1cccnc1NCc1ccc2c(c1)OCO2
CCc1nc(SCc2cccc(C(=O)OC)c2)[nH]c(=O)c1C#N
N#Cc1ccc(NC(=O)CSc2cnn[nH]2)cc1
CC(=O)c1cc(C#N)c(SCc2ccccn2)nc1C
COC(=O)CC(=O)CSc1nc2c(cc1C#N)CCC2
N#Cc1ccc(NC(=O)CSc2nnc[nH]2)cc1
Cc1nc(SCC#N)c2oc3ccccc3c2n1
N#CCNC(=O)C1CC(=O)N(CCc2ccc(F)cc2)C1
C=CCn1c(SCC#N)nc2sc(CC)cc2c1=O
CCc1nnc(SCC(=O)Nc2sc3c(c2C#N)CCCC3)[nH]1
COC(=O)CSc1nc(C)c(C)c(C)c1C#N
N#Cc1c(NC(=O)CSc2ncccn2)sc2c1CCC2
Cc1nc(SCC(=O)O)c(C#N)c(C)c1C
Cc1nc(SCC(N)=O)c(C#N)c(C)c1C
COCc1cc(C)nc(SCc2ccc(Cl)cc2)c1C#N
CCc1nc(SCC(=O)NCCc2ccccc2)[nH]c(=O)c1C#N
CCN1CCN(CC(=O)C(C#N)c2ccccc2)CC1
N#CCCCN1C(=O)C(=O)c2ccccc21
CN1CCN(CC(=O)C(C#N)c2ccccc2)CC1
Cc1nc(N(CCC#N)CCC#N)sc1C(C)(C)C
N#Cc1cccnc1SCC(=O)Nc1ccc(Br)c(Cl)c1
Cc1cc(C)c(C#N)c(SCC(N)=O)n1
CC(=O)c1cc(C#N)c(SCC(=O)Nc2ccc(C(N)=O)cc2)nc1C
N#Cc1cccnc1NCc1cccnc1
Cc1cc(SC(C)C(=O)Nc2sc(C)c(C)c2C#N)ncn1
N#Cc1cnc(SCCOc2ccccc2)nc1N
Cc1cc2c(=O)n(C)c(SCC#N)nc2s1
CCc1nnc(NC(=O)CSc2nc3c(cc2C#N)CCCC3)s1
N#CC(C(=O)CN1CCOCC1)c1ccccc1
CCOC(=O)c1sc(NC(=O)CSc2ccccn2)c(C#N)c1C
N#CCN1CCN(CC(=O)c2ccc(Br)cc2)CC1
CCc1nc(SCC(=O)c2ccccc2)[nH]c(=O)c1C#N
COc1ccc(S(=O)(=O)NCC#N)cc1
COCc1cc(C)nc(SCC(=O)NC2CCCCC2)c1C#N
Cc1nc(SCC(=O)Nc2sc3c(c2C#N)CCCC3)oc1C
COCCNc1oc(COc2cccc(C)c2)nc1C#N
N#CCCn1nnc(-c2ccccc2F)n1
CN1CCc2nc(SCc3cccnc3)c(C#N)cc2C1
N#Cc1cccnc1SCC(=O)Nc1cccc(F)c1
N#CCC(=O)NS(=O)(=O)c1ccc(Cl)cc1
N#CCCCn1c(=O)oc2ccccc21
N#CCCS(=O)(=O)c1ccc(N)cc1
CC1CC(=O)C(C)(CCC#N)CN1C
N#CCC(=O)N1CCN(CCc2ccccc2)CC1
COCc1cc(C)nc(SCC(=O)NC2CCCCC2C)c1C#N
Cc1ccccc1NC(=O)c1cnc2nc(SCC#N)nn2c1C
N#CCCS(=O)(=O)c1ccc(Cl)c(Cl)c1
Cn1nnnc1SCC(=O)Nc1ccc(C#N)cc1
CC1CN(CC(=O)C(C#N)c2ccccc2)CC(C)O1
N#CCCCn1cnc2ccccc2c1=O
COc1cccc(NC(=O)CSc2nc(C)c(C)c(C)c2C#N)c1
CCc1nc(SCC(=O)Nc2ccccc2C)[nH]c(=O)c1C#N
Cc1nc(SCC(=O)Nc2sc3c(c2C#N)CCCC3)[nH]c(=O)c1CCO
N#Cc1ccc(OCCSc2ncccn2)cc1
N#Cc1ccc(-c2cccs2)nc1SCC(=O)Nc1nccs1
Cn1c(=O)c2ccccc2n(CC#N)c1=O
COc1cccc(-c2nc(CC#N)n[nH]2)c1
CCOC(=O)c1sc(C)c(C#N)c1N
CCc1nc(SCC(=O)Nc2cccc(C)c2C)[nH]c(=O)c1C#N
CCc1nnc(NC(=O)CSc2nc3c(cc2C#N)CCC3)s1
CCCSc1nc(C)cc(COC)c1C#N
CCc1nc(SCC(=O)Nc2cccc3ccccc23)[nH]c(=O)c1C#N
N#Cc1ccccc1OCCCn1cncn1
CCOC(=O)c1ccc(NC(=O)CSc2ncccc2C#N)cc1
CCc1nc(SC(C)C(=O)Nc2cc(C)ccc2C)[nH]c(=O)c1C#N
COc1ccc(C(=O)NCC#N)cc1
CCc1ccc(CCC(=O)Nc2sc3c(c2C#N)CCCC3)o1
COC(=O)c1ccc(NC(=O)CSc2ncccc2C#N)cc1
Cc1ccnc(SCC(=O)c2ccc(C#N)cc2)n1
N#CCCn1cc(CO)c(-c2ccccc2)n1
Cc1cc(C)nc(SCCCC#N)n1
CCOC(=O)C(C#N)C(=O)c1ccc(N)cc1
Cc1nnc(SCC(=O)Nc2ccc(C#N)cc2)s1
COc1ccc(C(=O)CSc2nc(C)ccc2C#N)cc1OC
N#CCNC1CC(=O)N(c2ccc(Br)cc2)C1=O
N#Cc1cc(C(=O)Nc2ccccc2)c(N)nc1SCC(N)=O
CCc1nc(SC(C)C(=O)Nc2ccccc2C)[nH]c(=O)c1C#N
COCCCNc1oc(-c2cccc(C)c2)nc1C#N
COCCCNc1oc(-c2ccccc2C)nc1C#N
COC(=O)Cn1cc(C#N)c2ccccc21
Cc1c(Cl)cccc1NC(=O)CSc1ncccc1C#N
Cc1c(F)cccc1NC(=O)CSc1ncccc1C#N
CCc1nc(SC(C)C(=O)Nc2ccc(C)cc2)[nH]c(=O)c1C#N
N#CC1(c2ccccc2)CCC(=O)N1CCO
CCc1ccc(NC(=O)C(C)Sc2nc(CC)c(C#N)c(=O)[nH]2)cc1
CCc1nc(SCC(=O)Nc2ccc(C)c(C)c2)[nH]c(=O)c1C#N
N#Cc1ccccc1OCCn1cncn1
CCc1nc(SCC(=O)Nc2ccc(C)cc2)[nH]c(=O)c1C#N
CCOc1ccc(C(=O)CC#N)cc1
COCCNc1oc(/C=C/c2cccs2)nc1C#N
N#Cc1ccccc1OCCCn1ccnc1
CCc1nc(SCC(=O)Nc2cc(C)cc(C)c2)[nH]c(=O)c1C#N
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 3 of 5.
Other Notes:
A SD file of the 3D binding coordinates is available.