Submission Details
Molecule(s):
CO[C@@]1(C(=O)Nc2cncc3cc(F)ccc23)CS(=O)(=O)Cc2ccc(Cl)cc21
CO[C@@]1(C(=O)Nc2cncc3ccc(S(C)(=O)=O)cc23)CS(=O)(=O)Cc2ccc(Cl)cc21
COc1cc2c(NC(=O)[C@]3(OC)CS(=O)(=O)Cc4ccc(Cl)cc43)cncc2cn1
COc1cc2cncc(NC(=O)[C@]3(OC)CS(=O)(=O)Cc4ccc(Cl)cc43)c2cn1
CO[C@@]1(C(=O)Nc2cncc3cnccc23)CS(=O)(=O)Cc2ccc(Cl)cc21
CO[C@@]1(C(=O)Nc2cncc3ccncc23)CS(=O)(=O)Cc2ccc(Cl)cc21
CO[C@@]1(C(=O)Nc2cncc3ccc(S(C)(=O)=O)cc23)CN(S(=O)(=O)N(C)C)Cc2ccccc21
CO[C@@]1(C(=O)Nc2cncc3ccc(F)cc23)CN(S(=O)(=O)N(C)C)Cc2ccc(Cl)cc21
CO[C@@]1(C(=O)Nc2cncc3cc(F)ccc23)CN(S(=O)(=O)N(C)C)Cc2ccc(Cl)cc21
Design Rationale:
Cyclic sulfones (6) and tetrahydroisoquinoline sulfamides (3), derived from the structural prototypes PET-UNK-1b92fa34-5 and PET-UNK-88d26eaf-1, with P1 variations intended to address potential metabolism at P1. Rationale for the methoxynaphthyridines is discussed in PET-UNK-f4e47ebd submission notes. This submission is related to the PET-UNK-1e13ef09 submission.
Other Notes:
Protein-ligand complexes (P0157 A chain) were energy-minimized using Szybki (MMFF94S; amide carbonyl O and isoquinoline N fixed at the positions of the crystallographic ligand). The PDB file associated with this submission contains the following: [1] P0157 A chain from energy-mimimized complex with PET-UNK-1b92fa34-5 [2] P0157 A chain crystallographic ligand (PET-UNK-29afea89-2) [3-4] Binding modes predicted for PET-UNK-1b92fa34-5 and PET-UNK-88d26eaf-1 [5-13] Binding modes predicted for designs 1-9