Submission Details
Molecule(s):
O=C(Nc1ccccc1)Nc1cccnc1F
O=C(CC1CCCCC1)Nc1cccnc1F
O=C(Nc1ccccc1)Nc1cccnc1Cl
O=C(CC1CCCCC1)Nc1cccnc1Cl
Nc1cnc(Cl)c(NC(=O)Nc2ccccc2)c1
CNc1cnc(Cl)c(NC(=O)Nc2ccccc2)c1
CN(C)c1cnc(Cl)c(NC(=O)Nc2ccccc2)c1
O=C(Nc1ccccc1)Nc1c(Cl)ncc2ncncc12
O=C(Nc1ccccc1)Nc1c(Cl)ncc2ncccc12
O=C(Nc1ccccc1)Nc1c(Cl)ncc2[nH]ccc12
O=C(Nc1ccccc1)Nc1c(Cl)ncn2nccc12
O=C(Nc1ccccc1)Nc1c(Cl)ncc2nccn12
O=C(Nc1ccccc1)Nc1c(Cl)ncc2[nH]cnc12
O=C(Nc1ccccc1)Nc1c(Cl)ncc2[nH]ncc12
O=C(Nc1ccccc1)Nc1c(Cl)ncc2nccnc12
Nc1cnc(Cl)c(NC(=O)CC2CCCCC2)c1
CNc1cnc(Cl)c(NC(=O)CC2CCCCC2)c1
CN(C)c1cnc(Cl)c(NC(=O)CC2CCCCC2)c1
O=C(CC1CCCCC1)Nc1c(Cl)ncc2ncncc12
O=C(CC1CCCCC1)Nc1c(Cl)ncc2ncccc12
O=C(CC1CCCCC1)Nc1c(Cl)ncc2[nH]ccc12
O=C(CC1CCCCC1)Nc1c(Cl)ncn2nccc12
O=C(CC1CCCCC1)Nc1c(Cl)ncc2nccn12
O=C(CC1CCCCC1)Nc1c(Cl)ncc2[nH]cnc12
O=C(CC1CCCCC1)Nc1c(Cl)ncc2[nH]ncc12
O=C(CC1CCCCC1)Nc1c(Cl)ncc2nccnc12
Design Rationale:
Design Objective: chloro-substituent to interact with HIS164 backbone carbonyl This submission builds on a prior submission, SPE-ELM-b65, in which the fluoro-substituent in those candidates compounds are replaced with a chloro-substituent. Also, two of those fluoro- compounds were omitted, so they are included in this set. The primary interactions for these compounds occur in the S1 binding pocket. HIS163 hydrogen bonds to the nitrogen in a pyrimidine ring (or analogous fused bicyclic ring with a nitrogen in a conserved location). The chloro-substituent possibly forms a halogen bond with the HIS164 backbone carbonyl. And the linker amide carbonyl forms a strong hydrogen bond with the backbone N-H group of GLU166. Finally, the reason for proposing so many variations of the ring system is to probe hydrogen bonding interactions, modulate the electronics of the ring, change angles slightly, and form polar interactions with proximal polar side chains. Ideally, all of these compounds could be tested and the best candidates carried forward for modifications and growth on the conserved ends of these molecules.