Submission Details
Molecule(s):
N#Cc1cccnc1SCC(=O)NC1CCCCC1
Cc1nc(SCC(=O)C2CC2)c(C#N)c(C)c1C
N#Cc1ccccc1OCCCCSc1ncccn1
CC(C)Cc1ccc(C#N)c(SCC(N)=O)n1
CC(Sc1nc2c(cc1C#N)CCCCC2)C(=O)O
N#Cc1cc2c(nc1SCC(=O)Nc1ccc(S(N)(=O)=O)cc1)CCCCC2
N#Cc1cc2c(nc1SCC(=O)Nc1ccc(S(N)(=O)=O)cc1)CCCC2
N#Cc1ccc(CSc2nnc(COc3ccccc3)o2)cc1
COc1ccc(-c2nnc(SCc3ccc(C#N)cc3)o2)cc1
Cn1c(SCc2cccc(C#N)c2)nc2sc3c(c2c1=O)CCC3
CCS(=O)(=O)CCSc1nc2c(cc1C#N)CCCC2
N#Cc1cc2c(nc1SCc1ccncc1)CCCCC2
N#Cc1ccc(CSc2nc3ccccc3c(=O)[nH]2)cc1
N#Cc1cc2c(nc1SCCC1OCCO1)CCCC2
CC1(C)CC(=O)c2cc(C#N)c(SCC(N)=O)nc2C1
Cc1sc2nc(SCc3cccc(C#N)c3)n(C)c(=O)c2c1C
N#CCN(CC#N)C(=O)CSc1ccccc1
N#Cc1cc2c(nc1SCc1ccncc1)CCC2
N#Cc1cc2c(nc1SCC(=O)O)CCCC2
N#Cc1cc2c(nc1SCC(N)=O)CCCC2
N#Cc1ccc(CSc2nc3c(c(=O)[nH]2)CCCC3)cc1
N#Cc1cc2c(nc1SCC(N)=O)CCCCC2
Cc1cc(C)c(C#N)c(SCc2ccc3c(c2)OCO3)n1
N#Cc1ccc(CSc2nc3ccccc3o2)c(Cl)c1
Cn1c(SCc2cccc(C#N)c2)nc2ccccc2c1=O
Cc1ccc(S(=O)(=O)NC(=O)CC#N)cc1
Cc1ccc(NC(=O)CSc2ncccc2C#N)cc1C
COc1ccc(-c2nnc(SCc3cccc(C#N)c3)o2)cc1
N#Cc1ccc(CSc2ncccn2)cc1
N#CCCSCc1nc2ccccc2[nH]1
N#Cc1cccc(CSc2nc3ccccc3o2)c1
COc1cc(C2(C#N)CCCC2)ccc1O
N#Cc1ccc(CSc2nc3c(c(=O)[nH]2)CCC3)cc1
N#Cc1ccc(CSc2nnc(-c3ccccc3)o2)cc1
Cc1nc(SCc2ccc(C#N)cc2)nc2c1CCCC2
N#Cc1c(NC(=O)CSc2ccccn2)sc2c1CCCCC2
CSc1cccc(NC(=O)CSc2ncccc2C#N)c1
N#Cc1ccc(CSc2nc3ccc(Br)cc3[nH]2)cc1
CCCc1oc(C#N)cc1CSc1nnc(N)s1
N#Cc1cc2c(nc1SCc1nc3ccccc3[nH]1)CCC2
Cc1cc(-c2ccccc2)nc(SCc2ccc(C#N)cc2)n1
N#Cc1cc2c(nc1SCc1cccnc1)CCCCC2
Cc1cccc(NC(=O)CSc2ncccc2C#N)c1
N#Cc1ccc(CSc2ccc3ccccc3n2)cc1
CCC1CCc2c(sc(NC(=O)CCC(=O)O)c2C#N)C1
N#Cc1cc2c(nc1SC1CCCCC1O)CCCC2
Cc1cc(SCc2ccc(C#N)cc2)nc2ccccc12
N#Cc1ccc(-c2ccccc2)nc1SCc1ccc(C(=O)O)cc1
N#CCCCCn1nnc(-c2ccc(Cl)cc2)n1
Cc1cc(C)c(C#N)c(SCc2ccc(C(=O)O)cc2)n1
Cc1ccc(Cl)cc1NC(=O)CSCC#N
Cc1nnc(SCc2ccc(C#N)cc2)[nH]1
Cc1cc(C)c(C#N)c(SC2CCCCC2=O)n1
Cc1ccc2nc(SCCC#N)nc(C)c2c1
Cc1nnc(SCc2ccc(C#N)cc2)s1
Cc1sc(NC(=O)CCCC(=O)O)c(C#N)c1C
Cc1cc(C)c(C#N)c(SCc2ccc(Cl)nc2)n1
Cn1c(SCc2ccc(C#N)cc2Cl)nc2ccccc21
CCc1ccc(NC(=O)CSCC#N)cc1
COc1ccc(C(C)=O)cc1CSCCC#N
N#CCSCC(=O)Nc1ccccc1
N#Cc1ccc(CSCC(=O)O)cc1
N#Cc1ccccc1COc1ccc(C(=O)O)cc1
CC1CCc2c(sc3ncnc(SCC#N)c23)C1
Cc1ccc(C#N)c(SCc2ccc(C(=O)O)cc2)n1
Cc1nn(-c2nc3ccccc3s2)c(O)c1CCC#N
N#Cc1c(NC(=O)CSc2ncn(-c3ccccc3)n2)sc2c1CCCC2
N#CCSCC(=O)Nc1ccc(Br)cc1
CCOC(=O)C(=O)Nc1sc2c(c1C#N)CCC(C)C2
CC(=O)c1cc(C#N)c(SCCC(C)C)nc1C
N#Cc1c(NC(=O)CCC(=O)O)sc2c1CCCCC2
N#CCCSCc1ccc2oc(C(=O)O)cc2c1
N#Cc1ccc(CSc2nc(-c3ccccc3)cc(=O)[nH]2)cc1
CC(C)(C)c1cc(CCCC#N)cc(C(C)(C)C)c1O
C=CCSc1nc2c(cc1C#N)CCC2
C=C(C)CSc1nc2c(cc1C#N)CCC2
COc1ccc(CSc2nc(C)cc(C)c2C#N)cc1
Cc1ccc(NC(=O)CSCC#N)cc1
C=CCSc1nc2c(cc1C#N)CCCC2
CCCCSc1nc2c(cc1C#N)CCC2
CCCCSc1nc2c(cc1C#N)CCCC2
CCCC1CCc2c(sc(NC(=O)CCC(=O)O)c2C#N)C1
CC(=O)c1cc(CSc2nc(-c3cccs3)ccc2C#N)cs1
N#Cc1ccc(CSc2nc3ccccc3s2)cc1
N#CC1C(c2ccsc2)C(C(N)=O)C(=O)NC1(O)c1ccccc1
CCCCSc1nc(C)c(C(C)=O)cc1C#N
N#Cc1ccccc1COC(=O)c1ccccn1
Cc1cc(C)c2nc(SCC#N)cc(C)c2c1
Cc1cc(SCC#N)nc2c(C)cccc12
COc1cccc(CSc2nc3c(cc2C#N)CCC3)c1
CSc1nc2c(cc1C#N)CCCCC2
C#CCSc1nc2c(cc1C#N)CCC2
COc1cccc(CSc2nc3c(cc2C#N)CCCCC3)c1
Cc1ccc(S(=O)(=O)CCC#N)cc1C
Cc1cc(SCC#N)nc2ccccc12
C#CCSc1nc2c(cc1C#N)CCCC2
N#Cc1cccc(OCc2ccc(Cl)c(Cl)c2)c1
CC1(C)CC(=O)C(CCC#N)C(=O)C1
N#CCC1CCS(=O)(=O)C1
N#Cc1cccc(OCc2cccc(I)c2)c1
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 5 of 5.
Other Notes:
A SD file of the 3D binding coordinates is available.