Submission Details
Molecule(s):
Cc1n[nH]c(C(=O)N2CCC3CN(Cc4nnsc4Cl)CC32)c1O
O=C1CCC(c2nnc(N3CCCC3)n2CCNC(=O)c2cccs2)N1
Cn1cc(C2CN(C(=O)c3cscn3)CC2NC2CCNC2=O)cn1
CC1CCN(C(=O)c2cc[nH]n2)C(CNc2nc(C3CCC3)ns2)C1
Cc1nc(CCn2c(C3CCC(=O)N3)nnc2N2CCOC(C)(C)C2)n[nH]1
OC1(Cn2c(-c3cc(Br)c[nH]3)nnc2N2CCCC2)CCCCCC1
O=C1CN(c2nnc(C3CCC(=O)N3)n2CCn2cc(Cl)cn2)CCN1
Cn1cc(Nc2nnc(C3CCC(=O)N3)n2CCN2CCCC(C)(C)C2)cn1
Cc1cc(CC2CN(Cc3ccc(C#CC(C)(C)O)s3)CC2O)on1
O=C(c1cc[nH]n1)N1CC(NCc2noc(C3CC3)n2)C(C(F)(F)F)C1
O=C(Cc1cccc(F)c1)NCCn1c(C2CCC(=O)N2)nnc1N1CCSCC1
CCSc1cc(Cn2c(C3CCC(=O)N3)nnc2N2CCC(C(N)=O)CC2)ccn1
CC(C)N1CCC(O)(Cn2c(-c3ccc[nH]3)nnc2N(C)Cc2cnn(C)c2)CC1
CC(C)(Cn1c(C2CCC(=O)N2)nnc1N1CCCC(C(N)=O)C1)c1ccccc1F
CC(=O)N1CCN(c2nnc(C3CCC(=O)N3)n2CC(=O)Nc2c(C)cccc2C)CC1
NC(=O)C1CCN(c2nnc(C3CCC(=O)N3)n2CCc2cc(F)cc(F)c2)CC1
O=C1CN(c2nnc(C3CCC(=O)N3)n2CCc2ccsc2)CCN1
CC1CN(C(=O)c2n[nH]c3c2CCC3)CC1NCc1nnsc1Cl
Cc1cc(NC2CCCCC2NC(=O)C2CCC(=O)NC2)n2ncnc2n1
O=S(=O)(NC1CCCCCC1)c1ccsc1-c1nc(C2CCCN2)no1
Cc1nc(Cn2c(C3CCC(=O)N3)nnc2N2CCNC(=O)C2)sc1C
Cc1nnc(Cn2c(C3CCC(=O)N3)nnc2N2CCNC(=O)C2)s1
O=C1CCC(c2nnc(N3CCC(CO)CC3)n2CCSc2ccccc2)N1
O=C1CCCCCN1CCCn1c(-c2ccc[nH]2)nnc1N1CCC(CO)CC1
CC1CCCN(c2nnc(C3CCC(=O)N3)n2CC(=O)Nc2ccc(F)cc2)CC1
Design Rationale:
The binding poses of x0072, x0161, x0195, x0434, and x1458 were chosen and merged to construct a pharmacophore template using Molegro Virtual Docker (MVD). Compounds were screened from Enamine REAL database by template docking using MVD. The final list of 25 compounds was selected according to several types of scoring functions.
Other Notes:
All these compounds are derived from the Enamine REAL database, so their availability is high. The submissions so far include a lot of amides/sulfonyls. So I avoided those structures as much as possible except tertiary amides and lactams, to improve the chemical diversity, membrane permeability and biostability. You can incorporate covalent warheads after finding hits. Compound list: REALPV-000051523242, ClC=1SN=NC=1CN(C2)CC3C2CCN3C(=O)C=4NN=C(C)C=4O REALPV-002045824567, O=C(N1)CCC1C2=NN=C(N3CCCC3)N2CCNC(=O)C=4SC=CC=4 REALPV-000075146668, O=C(C1=CSC=N1)N(C2)CC(C3=CN(N=C3)C)C2NC4CCNC4=O REALPV-000006496640, O=C(C=1C=CNN=1)N2CCC(C)CC2CNC(=N3)SN=C3C4CCC4 REALPV-002012910222, O=C(N1)CCC1C2=NN=C(N3CCOC(C)(C3)C)N2CCC4=NNC(C)=N4 REALPV-002045938854, BrC(C=1)=CNC=1C2=NN=C(N3CCCC3)N2CC4(O)CCCCCC4 REALPV-002045866855, ClC(=C1)C=NN1CCN2C(C3CCC(N3)=O)=NN=C2N4CCNC(=O)C4 REALPV-002034954482, O=C(N1)CCC1C2=NN=C(NC3=CN(N=C3)C)N2CCN4CC(C)(C)CCC4 MOLPORT046-524-365, OC(C)(C)C#CC(S1)=CC=C1CN(C2)CC(O)C2CC=3ON=C(C)C=3 REALPV-000098404655, FC(F)(F)C1CN(C(C=2C=CNN=2)=O)CC1NCC(N=3)=NOC=3C4CC4 REALPV-002045727683, FC(=C1)C=CC=C1CC(=O)NCCN2C(C3CCC(N3)=O)=NN=C2N4CCSCC4 REALPV-002032287891, O=C(N1)CCC1C2=NN=C(N3CCC(CC3)C(=O)N)N2CC(C=4)=CC=NC=4SCC REALPV-002006901178, OC1(CCN(CC1)C(C)C)CN2C(C3=CC=CN3)=NN=C2N(C)CC4=CN(C)N=C4 REALPV-002004216588, FC1=CC=CC=C1C(C)(C)CN2C(C3CCC(N3)=O)=NN=C2N(C4)CCCC4C(N)=O REALPV-002002816146, O=C(C)N(CC1)CCN1C2=NN=C(C3CCC(N3)=O)N2CC(=O)NC=4C(C)=CC=CC=4C REALPV-002045639389, FC(C=1)=CC(F)=CC=1CCN2C(C3CCC(N3)=O)=NN=C2N4CCC(C(=O)N)CC4 REALPV-002045866790, O=C(C1)NCCN1C2=NN=C(C3CCC(N3)=O)N2CCC4=CSC=C4 REALPV-000061775807, ClC=1SN=NC=1CNC(C2)C(C)CN2C(=O)C=3C=4CCCC=4NN=3 REALPV-000005281048, O=C(C1CCC(NC1)=O)NC2CCCCC2NC=3N4N=CN=C4N=C(C)C=3 REALZ2442610555, O=S(=O)(NC1CCCCCC1)C=2C=CSC=2C(=N3)ON=C3C4NCCC4 REALPV-002009376810, O=C(N1)CCC1C2=NN=C(N3CCNC(C3)=O)N2CC=4SC(C)=C(C)N=4 REALPV-002013544673, O=C(N1)CCC1C2=NN=C(N3CCNC(C3)=O)N2CC=4SC(C)=NN=4 REALPV-002045821025, O=C(N1)CCC1C2=NN=C(N3CCC(CC3)CO)N2CCSC=4C=CC=CC=4 REALPV-002045832122, O=C1CCCCCN1CCCN2C(C3=CC=CN3)=NN=C2N(CC4)CCC4CO REALPV-002014815907, FC(=CC=1)C=CC=1NC(=O)CN2C(C3CCC(N3)=O)=NN=C2N4CCC(C)CCC4