Submission Details
Molecule(s):
CC(=O)c1cc(C#N)c(SCC(=O)c2ccc(O)c(O)c2)nc1C
Cc1nc(SCC(=O)Nc2sc(C)c(C)c2C#N)[nH]c(=O)c1CCO
N#CCNC(=O)CCn1c(=O)[nH]c2ccccc2c1=O
N#Cc1ccccc1OCCOCCN1CCOCC1
CCOC(=O)CC(=O)CSc1nc(-c2cccnc2)ccc1C#N
CCOC(=O)CC(=O)CSc1nc(C)cc(C)c1C#N
COC(=O)CSc1nsc(SCC(=O)OC)c1C#N
COC(=O)CC(=O)CSc1nc(C)cc(C)c1C#N
N#Cc1cnc(SCc2nc3ccccc3c(=O)[nH]2)nc1N
CCCOC(=O)CSc1nc(C)c(C)c(C)c1C#N
Cc1cc(C)c(C#N)c(SCC(=O)NCC(=O)O)n1
CC(=O)CSc1nsc(SCC(C)=O)c1C#N
CCc1nc(SCC#N)c2oc3ccccc3c2n1
COC(=O)c1ccc2oc(=O)n(CC#N)c2c1
N#Cc1cccnc1SCC(=O)Nc1nccs1
Cc1ccc(CCC(=O)C(C#N)c2nc3ccccc3s2)o1
CSc1nc(N)nc(SCC(=O)c2ccc(Cl)s2)c1C#N
COCc1cc(C)nc(SCC(=O)Nc2ccccc2O)c1C#N
CCCC(=O)N1CCC(C(=O)NCC#N)CC1
Cc1ccnc(SCC(=O)Nc2sccc2C#N)n1
Cc1cc(C)c(C#N)c(SCC(=O)OC(C)C)n1
CCOc1ccc2nc(SCCC#N)nc(C)c2c1
N#Cc1ccccc1OCCCN1CCOCC1
Cc1ccc(C#N)c(SCC(=O)O)n1
C=COC(=O)CSc1nc(C)cc(C)c1C#N
COCCNc1oc(COc2ccc(Br)cc2)nc1C#N
Cc1nc(SCC(=O)Nc2sc3c(c2C#N)CCC3)[nH]c(=O)c1CCO
N#CCCn1c(CC(N)=O)nc2ccccc21
Cc1cc(C)c(C#N)c(SCC(=O)Nc2nccs2)n1
COCc1cc(C)nc(SCC(=O)NCc2ccccc2)c1C#N
CSc1nc(N)nc(SCc2ccccn2)c1C#N
CSc1nsc(SCC(=O)Nc2ccc(C#N)cc2)n1
N#Cc1cnc(SCCCOc2ccc(Cl)cc2)nc1N
CCOC(=O)c1sc(NC(=O)CSc2ncccn2)c(C#N)c1C
N#Cc1ccsc1NC(=O)CSc1nc[nH]n1
CCc1nc(SCC(=O)NCc2ccccc2)[nH]c(=O)c1C#N
Cc1ccc(C#N)c(SCC(N)=O)n1
CSc1nc(N)nc(SCC(=O)c2ccc3c(c2)OCO3)c1C#N
CCc1nc(C)c(C#N)c2cc(OC)c(OC)cc12
COc1ccc(NC(=O)CSCC#N)cc1
Cc1cc(C)c(C#N)c(SCCN2CCOCC2)n1
Cn1ccnc1SCC(=O)Nc1ccc(C#N)cc1
Cc1ccnc(SCC(=O)Nc2ccc(C#N)cc2)n1
CCOC(=O)C1CCN(CCCOc2ccccc2C#N)CC1
N#CCCCN1C(=O)C(O)(CC(=O)c2ccco2)c2ccccc21
N#Cc1cnc(SCC(=O)Nc2ccccc2F)nc1N
Cc1nc(C#N)c(NCc2ccc3c(c2)OCO3)o1
N#CCSCC(=O)Nc1ccc(Cl)cc1
CCN1CCN(CCOCCOc2ccccc2C#N)CC1
Cc1nnc(SCC(=O)Nc2sccc2C#N)s1
CSc1nc2ccccc2n1CCCC#N
N#CCCn1c(=O)n(CCC#N)c2ccccc21
Cn1cnnc1SCC(=O)Nc1ccc(C#N)cc1
N#CCSCC(=O)Nc1ccc(F)cc1
CC1(C)Cc2nc(NCc3cccnc3)c(C#N)cc2CO1
CN1CCN(CCCOc2ccccc2C#N)CC1
CC(=O)Nc1ccc(S(=O)(=O)N(C)CCC#N)cc1
COCCNc1oc(-c2ccccc2F)nc1C#N
CC1(C)NC(=O)N(CCCCOc2ccccc2C#N)C1=O
COC(=O)COc1nc(C)cc(C)c1C#N
Cn1ccnc1SCC(=O)Nc1sccc1C#N
N#CCCn1cc(CO)c(-c2ccc(Cl)cc2)n1
COc1ccc(-c2cc(O)n(CCC#N)n2)cc1
N#Cc1ccccc1OCCN1CCN(CCO)CC1
CN(C)CCNCCCOc1ccccc1C#N
Cc1c(C(=O)Nc2ccccc2)cnc2nc(SCC#N)nn12
CSc1nc(N)nc(SCc2cccnc2)c1C#N
CN(CCC#N)CC(=O)Nc1ccc(S(N)(=O)=O)cc1
N#Cc1ccccc1OCCCCn1cncn1
COc1ccc(CNc2oc(C)nc2C#N)cc1
COc1ccc(NC(=O)CSc2ncc3c(c2C#N)CCC3)cc1
COCc1cc(C)nc(SCCOc2ccccc2)c1C#N
N#Cc1cccnc1NCc1ccncc1
COCCCNc1oc(-c2ccccc2F)nc1C#N
CCc1nc(SC(C)C(=O)Nc2ccccc2Cl)[nH]c(=O)c1C#N
CCc1nc(SCC(=O)OCc2ccccc2)[nH]c(=O)c1C#N
N#CCC(=O)c1ccc2c(c1)OCCO2
COc1ccc(-c2nn(CCC#N)cc2CO)cc1
COC(=O)c1ccc(COc2nc(C)cc(C)c2C#N)o1
CCc1nnc(NC(=O)CSc2nc(C)cc(C)c2C#N)s1
N#CCCNCC1COc2ccccc2O1
COc1ccc(NC(=O)CSc2nc(C)c(C)cc2C#N)cc1
CN(C)CCCNc1oc(-c2ccccc2F)nc1C#N
COCCCNc1oc(-c2ccccc2Cl)nc1C#N
N#CCCn1cc(CO)c(-c2ccc(F)cc2)n1
CCOC1CN=C2C(C#N)=CC=CN21
COCCNc1oc(-c2ccccc2Cl)nc1C#N
COc1ccc(NC(=O)CSc2nc(C)cc(C)c2C#N)cc1
COCCNc1oc(-c2cccc(Cl)c2)nc1C#N
CSc1nc(N)nc(SCc2ccc(Cl)nc2)c1C#N
CC1CN(CCOCCOc2ccc(C#N)cc2)CC(C)O1
CCc1nc(SCC(=O)Nc2ccccc2Cl)[nH]c(=O)c1C#N
COCCCNc1oc(-c2ccc(F)cc2)nc1C#N
CN1CCN(CCOCCOc2ccccc2C#N)CC1
COCCCNc1oc(-c2ccc(OC)cc2)nc1C#N
CCOc1cc(-c2nnn(CC#N)n2)ccc1OC
CCOc1ccc(-c2nc(C#N)c(NCCOC)o2)cc1
N#Cc1nc(-c2ccccc2F)oc1NCCN1CCOCC1
COc1ccc(-c2nnn(CC#N)n2)cc1OC
COCCNc1oc(-c2ccc(OC)cc2)nc1C#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 2 of 5.
Other Notes:
A SD file of the 3D binding coordinates is available.